lgk974 profile

LGK974: a potent and specific small-molecule inhibitor of Porcupine (PORCN) acyltransferase [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

LGK974 : A carboxamide, the structure of which is that of acetamide substituted on carbon by a 2',3-dimethyl-2,4'-bipyridin-5-yl group and on nitrogen by a 5-(pyrazin-2-yl)pyridin-2-yl group. It is a highly potent, selective and orally bioavailable Porcupine inhibitor (a Wnt signalling inhibitor). [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

ID Source	ID
PubMed CID	46926973
CHEMBL ID	3188386
CHEBI ID	78030
SCHEMBL ID	1723611
MeSH ID	M0591586

Synonym
NCGC00347950-01
S7143
HY-17545
lgk974
MLS006011002
smr004702800
CHEBI:78030 ,
2-(2',3-dimethyl-2,4'-bipyridin-5-yl)-n-[5-(pyrazin-2-yl)pyridin-2-yl]acetamide
SCHEMBL1723611
2-(2',3-dimethyl-[2,4'-bipyridin]-5-yl)-n-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide
lgk 974
unii-u27f40013q
2-(2',3-dimethyl-(2,4'-bipyridin)-5-yl)-n-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide
U27F40013Q ,
(2,4'-bipyridine)-5-acetamide, 2',3-dimethyl-n-(5-(2-pyrazinyl)-2-pyridinyl)-
wnt-974 [who-dd]
1243244-14-5
lgk-974
wnt-974
wnt974
AC-30231
CHEMBL3188386 ,
AKOS025211913
bdbm50133870
J-005066
mfcd27501026
nvp-lgk974
HMS3653G11
gtpl11167
NCGC00347950-07
2-[5-methyl-6-(2-methyl-4-pyridyl)-3-pyridyl]-n-(5-pyrazin-2-yl-2-pyridyl)acetamide
SW211728-2
DB12561
lgk 974;lgk974; wnt974; wnt 974; wnt-974
BCP08495
Q27147596
lgk974 (wnt974)
EX-A1402
[2,4'-bipyridine]-5-acetamide, 2',3-dimethyl-n-[5-(2-pyrazinyl)-2-pyridinyl]-
SB19314
MS-20504
CCG-264701
CS3177
2-[5-methyl-6-(2-methylpyridin-4-yl)pyridin-3-yl]-n-(5-pyrazin-2-ylpyridin-2-yl)acetamide
NCGC00347950-11
AU-004/43508401
A890524
2-(2',3-dimethyl-[2,4'-bipyridin]-5-yl)-n-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide;lgk974
nsc-777639
nsc777639
NCGC00347950-02
lgk-974 (wnt974)
2-[(2p)-2',3-dimethyl[2,4'-bipyridin]-5-yl]-n-[(5p)-5-(pyrazin-2-yl)pyridin-2-yl]acetamide
o50 ,
porcn inhibitor iv
acotiamide impurity lgk
acotiamide impurity 43

Excerpt	Reference	Relevance
"LGK974 treatment suppressed the activation of NF-κB signaling and cytokine expression as well as the Wnt/β-catenin pathway in the livers of endotoxemic mice."	( LGK974 suppresses lipopolysaccharide-induced endotoxemia in mice by modulating the crosstalk between the Wnt/β-catenin and NF-κB pathways. Jang, J; Jho, EH; Kwon, YV; Lee, H; Sim, I; Song, J; Yoon, Y, 2021)	2.79

Excerpt	Reference	Relevance
" One approach is to block Wnt signalling through the use of orally bioavailable small molecules that prevent Wnt ligand secretion."	( The use of porcupine inhibitors to target Wnt-driven cancers. Ho, SY; Keller, TH, 2015)	0.42
" Furthermore, compound 59 exhibited good pharmacokinetic profiles with 30% oral bioavailability in rat."	( Design, synthesis, and evaluation of potent Wnt signaling inhibitors featuring a fused 3-ring system. He, S; Hu, Z; Li, J; Luo, L; Sun, Z; Wu, Y; Xu, Z; Zhang, H; Zhang, X; Zheng, J, 2016)	0.43
" The porcupine inhibitor LGK974, a novel orally bioavailable cancer therapeutic in Phase I clinical trials, induces potent Wnt signaling inhibition and leads to suppressed growth and progression of multiple types of cancers."	( Potent in vivo lung cancer Wnt signaling inhibition via cyclodextrin-LGK974 inclusion complexes. Chung, A; Guimaraes, PPG; Jacks, T; Langer, R; Mitchell, MJ; Oberli, M; Riley, RS; Spektor, R; Tammela, T; Tan, M; Viana, CTR; Wang, K; Wu, K, 2018)	1.02
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."	( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019)	0.51
"WNT974 is a potent, selective, and orally bioavailable first-in-class inhibitor of Porcupine, a membrane-bound O-acyltransferase required for Wnt secretion, currently under clinical development in oncology."	( Model-based dose selection to inform translational clinical oncology development of WNT974, a first-in-class Porcupine inhibitor. Huang, PH; Ji, Y; Myers, A; Woolfenden, S, 2022)	0.72

Excerpt	Relevance	Reference
"Patients (n = 94) received oral WNT974 at doses of 5-30 mg once-daily, plus additional dosing schedules."	( Phase 1 study of single-agent WNT974, a first-in-class Porcupine inhibitor, in patients with advanced solid tumours. Argilés, G; Connolly, RM; de Jonge, M; Dobson, JR; Garralda, E; Giannakis, M; Janku, F; Ji, Y; McLaughlin, ME; Moody, SE; Morawiak, J; Rodon, J; Seroutou, A; Smith, DC; Vaishampayan, U, 2021)	0.62
" During the dose-escalation part, various dosing regimens, including once or twice daily continuous and intermittent dosing at a dose range of 5-45 mg WNT974 were studied, however, the protocol-defined maximum tolerated dose (MTD) was not established based on dose-limiting toxicity."	( Model-based dose selection to inform translational clinical oncology development of WNT974, a first-in-class Porcupine inhibitor. Huang, PH; Ji, Y; Myers, A; Woolfenden, S, 2022)	0.72
"Patients received once-daily encorafenib and weekly cetuximab, in addition to once-daily WNT974, in sequential dosing cohorts."	( A Phase Ib/II Study of WNT974 + Encorafenib + Cetuximab in Patients With BRAF V600E-Mutant KRAS Wild-Type Metastatic Colorectal Cancer. De Braud, F; de Miguel, MJ; Edwards, M; Elez, E; Fiorella Dotti, K; Garralda, E; Geva, R; Litwiler, K; Morris, VK; Murphy, D; Tabernero, J; Tai, D; van Bussel, MTJ; Van Cutsem, E, 2023)	0.91

Role	Description
Wnt signalling inhibitor	A substance that inhibits any of the Wnt signalling pathway, a group of signal transduction pathways made of proteins that pass signals from outside of a cell through cell surface receptors to the inside of the cell.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Class	Description
bipyridines	Compounds containing a bipyridine group.
pyrazines
pyridines	Any organonitrogen heterocyclic compound based on a pyridine skeleton and its substituted derivatives.
secondary carboxamide	A carboxamide resulting from the formal condensation of a carboxylic acid with a primary amine; formula RC(=O)NHR(1).
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathway	Proteins	Compounds
Disease	1278	231
Diseases of signal transduction by growth factor receptors and second messengers	262	31
Signaling by WNT in cancer	9	3
LGK974 inhibits PORCN	1	1

Protein	Taxonomy	Measurement	Average (µ)	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
cytochrome P450 family 3 subfamily A polypeptide 4	Homo sapiens (human)	Potency	21.3174	0.0123	7.9835	43.2770	AID1645841
EWS/FLI fusion protein	Homo sapiens (human)	Potency	19.9242	0.0013	10.1577	42.8575	AID1259252; AID1259253; AID1259255; AID1259256
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Alpha-2B adrenergic receptor	Rattus norvegicus (Norway rat)	IC50 (µMol)	0.0009	0.0003	1.0914	7.7625	AID1322265
Alpha-2C adrenergic receptor	Rattus norvegicus (Norway rat)	IC50 (µMol)	0.0009	0.0003	1.0914	7.7625	AID1322265
Alpha-2A adrenergic receptor	Rattus norvegicus (Norway rat)	IC50 (µMol)	0.0009	0.0003	1.0691	7.7625	AID1322265
Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)	IC50 (µMol)	0.0004	0.0001	0.0318	0.1570	AID1257057; AID1457594
Protein-serine O-palmitoleoyltransferase porcupine	Mus musculus (house mouse)	IC50 (µMol)	0.0007	0.0004	0.0068	0.0250	AID1322265; AID1383152; AID1627466
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Process	via Protein(s)	Taxonomy
protein lipidation	Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)
glycoprotein metabolic process	Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)
Wnt signaling pathway	Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)
protein palmitoleylation	Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)
regulation of postsynaptic membrane neurotransmitter receptor levels	Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)
lipid modification	Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)
protein palmitoylation	Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)
Wnt protein secretion	Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
palmitoleoyltransferase activity	Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)
Wnt-protein binding	Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)
O-acyltransferase activity	Protein-serine O-palmitoleoyltransferase porcupine	Mus musculus (house mouse)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
endoplasmic reticulum	Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)
endoplasmic reticulum membrane	Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)
glutamatergic synapse	Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)
AMPA glutamate receptor complex	Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)
membrane	Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)
endoplasmic reticulum	Protein-serine O-palmitoleoyltransferase porcupine	Homo sapiens (human)
endoplasmic reticulum membrane	Protein-serine O-palmitoleoyltransferase porcupine	Mus musculus (house mouse)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (68)

Assay ID	Title	Year	Journal	Article
AID1383152	Inhibition of porcupine in mouse L Wnt3A cells co-cultured with HEK293 cells assessed as suppression of Wnt signaling after 48 hrs by Super-top flash reporter gene assay	2018	European journal of medicinal chemistry, Apr-10, Volume: 149	Discovery and characterization of a potent Wnt and hedgehog signaling pathways dual inhibitor.
AID1383193	Effect on Wnt3A levels in HEK293T cells transfected with pLibin-WNT3A plasmid at 100 nM after 48 hrs by Western blot method	2018	European journal of medicinal chemistry, Apr-10, Volume: 149	Discovery and characterization of a potent Wnt and hedgehog signaling pathways dual inhibitor.
AID1322265	Inhibition of porcupine in mouse L Wnt3A cells co-cultured with HEK293 cells after 48 hrs by Super-top flash reporter gene assay	2016	Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22	Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the 'reversed' amide scaffold.
AID1274448	Inhibition of Wnt signaling (unknown origin) expressed in mouse L Wnt3A cells co-cultured with HEK293 cells after 48 hrs by Super-top flash reporter gene assay	2016	European journal of medicinal chemistry, Jan-27, Volume: 108	Design, synthesis, and evaluation of potent Wnt signaling inhibitors featuring a fused 3-ring system.
AID1322274	Half life in rat liver microsomes at 1 uM preincubated for 10 mins followed by NADPH addition measured for 30 to 60 mins by LC-MS/MS analysis	2016	Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22	Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the 'reversed' amide scaffold.
AID1322269	Metabolic stability in rat plasma assessed as remaining compound levels at 1 uM after 8 hrs by LC-MS/MS analysis	2016	Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22	Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the 'reversed' amide scaffold.
AID1572810	Inhibition of Wnt/beta-catenin pathway in mouse L Wnt3A cells after 48 hrs by TOP-flash dual reporter gene assay	2019	Bioorganic & medicinal chemistry letters, 04-01, Volume: 29, Issue:7	Discovery and structure-activity relationship study of phthalimide-phenylpyridine conjugate as inhibitor of Wnt pathway.
AID1322273	Half life in human liver microsomes at 1 uM preincubated for 10 mins followed by NADPH addition measured for 30 to 60 mins by LC-MS/MS analysis	2016	Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22	Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the 'reversed' amide scaffold.
AID1383184	Inhibition of porcupine-mediated Wnt/beta-catenin signaling in human PA1 cells assessed as downregulation of disheveled 2 phosphorylation after 48 hrs by Western blot analysis	2018	European journal of medicinal chemistry, Apr-10, Volume: 149	Discovery and characterization of a potent Wnt and hedgehog signaling pathways dual inhibitor.
AID1274452	Effect on Wnt3A level in HEK293T cells transfected with pLibin-WNT3A plasmid at 0.1 uM after 48 hrs by Western blot technique	2016	European journal of medicinal chemistry, Jan-27, Volume: 108	Design, synthesis, and evaluation of potent Wnt signaling inhibitors featuring a fused 3-ring system.
AID1894735	Inhibition of Wnt signaling pathway in mouse TM3 cells harbouring STF-reporter luciferase gene co-cultured with mouse L Wnt-3A cells incubated for 24 hrs by Bright-Glo Luciferase Assay	2021	Journal of medicinal chemistry, 04-22, Volume: 64, Issue:8	Carboxylesterase Notum Is a Druggable Target to Modulate Wnt Signaling.
AID1257057	Inhibition of porcupine activity (unknown origin) expressed in human HT1080 cells assessed as suppression of Wnt3A-mediated super top flash activity by STF luciferase assay	2015	Bioorganic & medicinal chemistry letters, Dec-01, Volume: 25, Issue:23	The use of porcupine inhibitors to target Wnt-driven cancers.
AID1322266	Inhibition of porcupine in HEK293T cells transfected with pLibin-WNT3A plasmid assessed as reduction in Wnt3A secretion into cell culture medium at 0.1 uM after 48 hrs by Western blot method	2016	Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22	Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the 'reversed' amide scaffold.
AID1781278	Cytotoxicity against human MCF-10A cells assessed as cell growth inhibition measured after 72 hrs by MTS assay
AID1781276	Antiproliferative activity against human SW480 cells assessed as cell growth inhibition measured after 72 hrs by MTS assay
AID1383181	Inhibition of porcupine in HEK293 cells transfected with pLibin-WNT3A plasmid assessed as downregulation of disheveled 2 phosphorylation at 100 nM after 48 hrs by Western blot analysis	2018	European journal of medicinal chemistry, Apr-10, Volume: 149	Discovery and characterization of a potent Wnt and hedgehog signaling pathways dual inhibitor.
AID1627467	Aqueous solubility of compound in buffer of pH 6.8 after 24 hrs by UV-based high throughput assay	2016	ACS medicinal chemistry letters, Jul-14, Volume: 7, Issue:7	Discovery of Pyridinyl Acetamide Derivatives as Potent, Selective, and Orally Bioavailable Porcupine Inhibitors.
AID1383183	Inhibition of porcupine-mediated Wnt/beta-catenin signaling in human PA1 cells assessed as downregulation of Axin2 mRNA expression after 24 hrs by real-time PCR analysis	2018	European journal of medicinal chemistry, Apr-10, Volume: 149	Discovery and characterization of a potent Wnt and hedgehog signaling pathways dual inhibitor.
AID1627466	Inhibition of PORCN in mouse Leydig cells overexpressing Wnt3A co-cultured with TM3 cells transfected with Wnt-luciferase gene after 24 hrs by luminescence assay	2016	ACS medicinal chemistry letters, Jul-14, Volume: 7, Issue:7	Discovery of Pyridinyl Acetamide Derivatives as Potent, Selective, and Orally Bioavailable Porcupine Inhibitors.
AID1572809	Inhibition of Wnt/beta-catenin pathway in mouse L Wnt3A cells at 10 uM after 48 hrs by TOP-flash dual reporter gene assay relative to control	2019	Bioorganic & medicinal chemistry letters, 04-01, Volume: 29, Issue:7	Discovery and structure-activity relationship study of phthalimide-phenylpyridine conjugate as inhibitor of Wnt pathway.
AID1383180	Inhibition of porcupine in HEK293T cells transfected with pLibin-WNT3A plasmid assessed as reduction in Wnt3A secretion into cell culture medium at 100 nM after 48 hrs by Western blot method	2018	European journal of medicinal chemistry, Apr-10, Volume: 149	Discovery and characterization of a potent Wnt and hedgehog signaling pathways dual inhibitor.
AID1781275	Antiproliferative activity against human MDA-MB-468 cells assessed as cell growth inhibition measured after 72 hrs by MTS assay
AID1322275	Half life in mouse liver microsomes at 1 uM preincubated for 10 mins followed by NADPH addition measured for 30 to 60 mins by LC-MS/MS analysis	2016	Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22	Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the 'reversed' amide scaffold.
AID1383186	Inhibition of smo-mediated hedgehog signaling pathway in mouse NIH3T3 cells expressing GRE-Luc reporter gene assessed as inhibition of SAG-induced GRE-Luc reporter activity after 48 hrs by luminescence assay	2018	European journal of medicinal chemistry, Apr-10, Volume: 149	Discovery and characterization of a potent Wnt and hedgehog signaling pathways dual inhibitor.
AID1457594	Inhibition of porcupine (unknown origin)	2017	Journal of medicinal chemistry, 08-10, Volume: 60, Issue:15	Scaffold Hopping and Optimization of Maleimide Based Porcupine Inhibitors.
AID1781274	Antiproliferative activity against human MDA-MB-231 cells assessed as cell growth inhibition measured after 72 hrs by MTS assay
AID1383185	Inhibition of porcupine-mediated Wnt/beta-catenin signaling in human PA1 cells assessed as downregulation of LRP6 phosphorylation after 48 hrs by Western blot analysis	2018	European journal of medicinal chemistry, Apr-10, Volume: 149	Discovery and characterization of a potent Wnt and hedgehog signaling pathways dual inhibitor.
AID1322270	Intrinsic clearance in human liver microsomes at 1 uM preincubated for 10 mins followed by NADPH addition measured for 30 to 60 mins by LC-MS/MS analysis	2016	Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22	Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the 'reversed' amide scaffold.
AID1322267	Effect on Wnt3A level in HEK293T cells transfected with pLibin-WNT3A plasmid at 0.1 uM after 48 hrs by Western blot method	2016	Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22	Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the 'reversed' amide scaffold.
AID1274451	Inhibition of porcupine (unknown origin) in HEK293T cells transfected with pLibin-WNT3A plasmid assessed as reduction in Wnt3A secretion into cell culture medium at 0.1 uM after 48 hrs by Western blot technique	2016	European journal of medicinal chemistry, Jan-27, Volume: 108	Design, synthesis, and evaluation of potent Wnt signaling inhibitors featuring a fused 3-ring system.
AID1322271	Intrinsic clearance in rat liver microsomes at 1 uM preincubated for 10 mins followed by NADPH addition measured for 30 to 60 mins by LC-MS/MS analysis	2016	Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22	Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the 'reversed' amide scaffold.
AID1383182	Inhibition of porcupine in HEK293 cells transfected with pLibin-WNT3A plasmid assessed as downregulation of LRP6 phosphorylation at 100 nM after 48 hrs by Western blot analysis	2018	European journal of medicinal chemistry, Apr-10, Volume: 149	Discovery and characterization of a potent Wnt and hedgehog signaling pathways dual inhibitor.
AID1322268	Chemical stability in simulated gastric fluid assessed as remaining compound levels at 200 uM at 40 degC after 24 hrs by HPLC method	2016	Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22	Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the 'reversed' amide scaffold.
AID1383192	Inhibition of smo-mediated hedgehog signaling pathway in mouse NIH3T3-Luc cells assessed as downregulation of Gli mRNA expression at 1 uM after 48 hrs by real-time PCR analysis	2018	European journal of medicinal chemistry, Apr-10, Volume: 149	Discovery and characterization of a potent Wnt and hedgehog signaling pathways dual inhibitor.
AID1781277	Antiproliferative activity against human HCT-116 cells assessed as cell growth inhibition measured after 72 hrs by MTS assay
AID1322272	Intrinsic clearance in mouse liver microsomes at 1 uM preincubated for 10 mins followed by NADPH addition measured for 30 to 60 mins by LC-MS/MS analysis	2016	Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22	Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the 'reversed' amide scaffold.
AID1296008	Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening	2020	SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1	Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1347086	qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal	2020	Antiviral research, 01, Volume: 173	A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347106	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347090	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347091	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347107	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347092	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347098	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347096	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347108	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1508630	Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay	2021	Cell reports, 04-27, Volume: 35, Issue:4	A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347094	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347105	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347083	qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen	2020	Antiviral research, 01, Volume: 173	A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347097	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1346987	P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen	2019	Molecular pharmacology, 11, Volume: 96, Issue:5	A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347082	qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal	2020	Antiviral research, 01, Volume: 173	A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1745845	Primary qHTS for Inhibitors of ATXN expression
AID1347099	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347093	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347104	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347101	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347089	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347154	Primary screen GU AMC qHTS for Zika virus inhibitors	2020	Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49	Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347103	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347102	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1346986	P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen	2019	Molecular pharmacology, 11, Volume: 96, Issue:5	A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347095	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347100	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347411	qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary	2020	ACS chemical biology, 07-17, Volume: 15, Issue:7	High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347159	Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay	2020	Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49	Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347160	Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors	2020	Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49	Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	32 (59.26)	24.3611
2020's	22 (40.74)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	2 (3.70%)	5.53%
Reviews	3 (5.56%)	6.00%
Case Studies	0 (0.00%)	4.05%
Observational	0 (0.00%)	0.25%
Other	49 (90.74%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (2)

Trial Overview

Trial	Phase	Enrollment	Study Type	Start Date	Status
An Open Label, Non-randomized Phase II Trial Evaluating WNT974 in Patients With Metastatic Head and Neck Squamous Cell Carcinoma [NCT02649530]	Phase 2	0 participants (Actual)	Interventional		Withdrawn(stopped due to funding withdrawn)
A Phase I, Open-label, Dose Escalation Study of Oral LGK974 in Patients With Malignancies Dependent on Wnt Ligands [NCT01351103]	Phase 1	185 participants (Actual)	Interventional	2011-12-01	Active, not recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Substance	Relationship Strength	Studies	Trials	Classes	Roles
dimethyl sulfoxide Dimethyl Sulfoxide: A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during CRYOPRESERVATION. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation.. dimethyl sulfoxide : A 2-carbon sulfoxide in which the sulfur atom has two methyl substituents.	2.25	1	0	sulfoxide; volatile organic compound	alkylating agent; antidote; Escherichia coli metabolite; geroprotector; MRI contrast agent; non-narcotic analgesic; polar aprotic solvent; radical scavenger
melatonin [no description available]	2.31	1	0	acetamides; tryptamines	anticonvulsant; central nervous system depressant; geroprotector; hormone; human metabolite; immunological adjuvant; mouse metabolite; radical scavenger
n-acetylserotonin N-acetylserotonin : An N-acylserotonin resulting from the formal condensation of the primary amino group of serotonin with the carboxy group of acetic acid.	2.31	1	0	acetamides; N-acylserotonin; phenols	antioxidant; human metabolite; mouse metabolite; tropomyosin-related kinase B receptor agonist
theophylline [no description available]	2.31	1	0	dimethylxanthine	adenosine receptor antagonist; anti-asthmatic drug; anti-inflammatory agent; bronchodilator agent; drug metabolite; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; fungal metabolite; human blood serum metabolite; immunomodulator; muscle relaxant; vasodilator agent
aspirin Aspirin: The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5). acetylsalicylate : A benzoate that is the conjugate base of acetylsalicylic acid, arising from deprotonation of the carboxy group.. acetylsalicylic acid : A member of the class of benzoic acids that is salicylic acid in which the hydrogen that is attached to the phenolic hydroxy group has been replaced by an acetoxy group. A non-steroidal anti-inflammatory drug with cyclooxygenase inhibitor activity.	7.25	1	0	benzoic acids; phenyl acetates; salicylates	anticoagulant; antipyretic; cyclooxygenase 1 inhibitor; cyclooxygenase 2 inhibitor; drug allergen; EC 1.1.1.188 (prostaglandin-F synthase) inhibitor; geroprotector; non-narcotic analgesic; non-steroidal anti-inflammatory drug; plant activator; platelet aggregation inhibitor; prostaglandin antagonist; teratogenic agent
caffeine [no description available]	2.31	1	0	purine alkaloid; trimethylxanthine	adenosine A2A receptor antagonist; adenosine receptor antagonist; adjuvant; central nervous system stimulant; diuretic; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; environmental contaminant; food additive; fungal metabolite; geroprotector; human blood serum metabolite; mouse metabolite; mutagen; plant metabolite; psychotropic drug; ryanodine receptor agonist; xenobiotic
celecoxib [no description available]	2.11	1	0	organofluorine compound; pyrazoles; sulfonamide; toluenes	cyclooxygenase 2 inhibitor; geroprotector; non-narcotic analgesic; non-steroidal anti-inflammatory drug
fluorouracil Fluorouracil: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.. 5-fluorouracil : A nucleobase analogue that is uracil in which the hydrogen at position 5 is replaced by fluorine. It is an antineoplastic agent which acts as an antimetabolite - following conversion to the active deoxynucleotide, it inhibits DNA synthesis (by blocking the conversion of deoxyuridylic acid to thymidylic acid by the cellular enzyme thymidylate synthetase) and so slows tumour growth.	2.21	1	0	nucleobase analogue; organofluorine compound	antimetabolite; antineoplastic agent; environmental contaminant; immunosuppressive agent; radiosensitizing agent; xenobiotic
temozolomide [no description available]	2.11	1	0	imidazotetrazine; monocarboxylic acid amide; triazene derivative	alkylating agent; antineoplastic agent; prodrug
serine Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.. serine : An alpha-amino acid that is alanine substituted at position 3 by a hydroxy group.	2.41	1	0	L-alpha-amino acid; proteinogenic amino acid; serine family amino acid; serine zwitterion; serine	algal metabolite; Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite
histidine Histidine: An essential amino acid that is required for the production of HISTAMINE.. L-histidine : The L-enantiomer of the amino acid histidine.. histidine : An alpha-amino acid that is propanoic acid bearing an amino substituent at position 2 and a 1H-imidazol-4-yl group at position 3.	2.41	1	0	amino acid zwitterion; histidine; L-alpha-amino acid; polar amino acid zwitterion; proteinogenic amino acid	algal metabolite; Escherichia coli metabolite; human metabolite; micronutrient; mouse metabolite; nutraceutical; Saccharomyces cerevisiae metabolite
quinazolines Quinazolines: A group of aromatic heterocyclic compounds that contain a bicyclic structure with two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring.. quinazoline : A mancude organic heterobicyclic parent that is naphthalene in which the carbon atoms at positions 1 and 3 have been replaced by nitrogen atoms.. quinazolines : Any organic heterobicyclic compound based on a quinazoline skeleton and its substituted derivatives.	2.25	1	0	azaarene; mancude organic heterobicyclic parent; ortho-fused heteroarene; quinazolines
indazoles Indazoles: A group of heterocyclic aromatic organic compounds consisting of the fusion of BENZENE and PYRAZOLES.	2.11	1	0	indazole
pyrazines Pyrazines: A heterocyclic aromatic organic compound with the chemical formula C4H4N2.. pyrazine : A diazine that is benzene in which the carbon atoms at positions 1 and 4 have been replaced by nitrogen atoms.	9.05	37	1	diazine; pyrazines	Daphnia magna metabolite
paraquat Paraquat: A poisonous dipyridilium compound used as contact herbicide. Contact with concentrated solutions causes irritation of the skin, cracking and shedding of the nails, and delayed healing of cuts and wounds.. paraquat : An organic cation that consists of 4,4'-bipyridine bearing two N-methyl substituents loctated at the 1- and 1'-positions.	2.17	1	0	organic cation	geroprotector; herbicide
camptothecin NSC 100880: carboxylate (opened lactone) form of camptothecin; RN refers to (S)-isomer; structure given in first source	2.11	1	0	delta-lactone; pyranoindolizinoquinoline; quinoline alkaloid; tertiary alcohol	antineoplastic agent; EC 5.99.1.2 (DNA topoisomerase) inhibitor; genotoxin; plant metabolite
paclitaxel Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL).	2.21	1	0	taxane diterpenoid; tetracyclic diterpenoid	antineoplastic agent; human metabolite; metabolite; microtubule-stabilising agent
irinotecan [no description available]	2.11	1	0	carbamate ester; delta-lactone; N-acylpiperidine; pyranoindolizinoquinoline; ring assembly; tertiary alcohol; tertiary amino compound	antineoplastic agent; apoptosis inducer; EC 5.99.1.2 (DNA topoisomerase) inhibitor; prodrug
triazoles Triazoles: Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.. triazoles : An azole in which the five-membered heterocyclic aromatic skeleton contains three N atoms and two C atoms.	2.11	1	0	1,2,3-triazole
coenzyme a [no description available]	2.41	1	0	adenosine 3',5'-bisphosphate	coenzyme; Escherichia coli metabolite; mouse metabolite
artesunic acid [no description available]	2.41	1	0
methotrexate [no description available]	2.31	1	0	dicarboxylic acid; monocarboxylic acid amide; pteridines	abortifacient; antimetabolite; antineoplastic agent; antirheumatic drug; dermatologic drug; DNA synthesis inhibitor; EC 1.5.1.3 (dihydrofolate reductase) inhibitor; immunosuppressive agent
nsc 668036 NSC 668036: structure in first source	2.61	2	0
puromycin [no description available]	2.25	1	0	puromycins	antiinfective agent; antimicrobial agent; antineoplastic agent; EC 3.4.11.14 (cytosol alanyl aminopeptidase) inhibitor; EC 3.4.14.2 (dipeptidyl-peptidase II) inhibitor; nucleoside antibiotic; protein synthesis inhibitor
palmitoyl coenzyme a Palmitoyl Coenzyme A: A fatty acid coenzyme derivative which plays a key role in fatty acid oxidation and biosynthesis.. palmitoyl-CoA : A long-chain fatty acyl-CoA resulting from the formal condensation of the carboxy group of hexadecanoic acid with the thiol group of coenzyme A.	2.41	1	0	11,12-saturated fatty acyl-CoA; 3-substituted propionyl-CoA; long-chain fatty acyl-CoA; palmitoyl bioconjugate	Escherichia coli metabolite; mouse metabolite
salinomycin salinomycin: from Streptomyces albus; RN given refers to parent cpd; structure	2.11	1	0	polyketide; spiroketal	animal growth promotant; potassium ionophore
icg 001 [no description available]	2.31	1	0	peptide
gdc 0449 HhAntag691: inhibits the hedgehog pathway and ABC transporters; has antineoplastic activity	2.17	1	0	benzamides; monochlorobenzenes; pyridines; sulfone	antineoplastic agent; Hedgehog signaling pathway inhibitor; SMO receptor antagonist; teratogenic agent
iwr-1 endo IWR-1-endo : A dicarboximide having an endo bridged phthalimide structure, substituted at nitrogen by a 4-(quinolin-8-ylcarbamoyl)benzoyl group.	2.31	1	0	benzamides; bridged compound; dicarboximide; quinolines	axin stabilizer; Wnt signalling inhibitor
encorafenib encorafenib: a BRAF inhibitor	3.99	1	1
wnt-c59 2-(4-(2-methylpyridin-4-yl)phenyl)-N-(4-(pyridin-3-yl)phenyl)acetamide: a PORCN acyltransferase inhibitor; structure in first source	3.61	2	0
g007-lk G007-LK: potent and specific small-molecule tankyrase inhibitor; structure in first source	2.11	1	0
icg 001 ICG 001: PRI-724 is an enantiomer of ICG-001; binds to cAMP response element-binding protein; structure in first source	2.66	2	0
dacarbazine (E)-dacarbazine : A dacarbazine in which the N=N double bond adopts a trans-configuration.	2.11	1	0	dacarbazine
xav939 XAV939: selectively inhibits beta-catenin-mediated transcription; structure in first source. XAV939 : A thiopyranopyrimidine in which a 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine skeleton is substituted at C-4 by a hydroxy group and at C-2 by a para-(trifluoromethyl)phenyl group.	2.54	2	0	(trifluoromethyl)benzenes; thiopyranopyrimidine	tankyrase inhibitor
pyrimidinones Pyrimidinones: Heterocyclic compounds known as 2-pyrimidones (or 2-hydroxypyrimidines) and 4-pyrimidones (or 4-hydroxypyrimidines) with the general formula C4H4N2O.	2.66	2	0

Condition	Indicated	Relationship Strength	Studies	Trials
Benign Neoplasms [description not available]	0	7.7	8	1
Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	0	7.7	8	1
Congenital Zika Syndrome [description not available]	0	2.25	1	0
Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	0	2.61	2	0
Zika Virus Infection A viral disease transmitted by the bite of AEDES mosquitoes infected with ZIKA VIRUS. Its mild DENGUE-like symptoms include fever, rash, headaches and ARTHRALGIA. The viral infection during pregnancy, in rare cases, is associated with congenital brain and ocular abnormalities, called Congenital Zika Syndrome, including MICROCEPHALY and may also lead to GUILLAIN-BARRE SYNDROME.	0	2.25	1	0
Milk-Alkali Syndrome [description not available]	0	3.99	1	1
Colorectal Cancer [description not available]	0	9.83	6	1
Hypercalcemia Abnormally high level of calcium in the blood.	0	3.99	1	1
Colorectal Neoplasms Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.	0	4.83	6	1
Breast Cancer [description not available]	0	2.21	1	0
Breast Neoplasms Tumors or cancer of the human BREAST.	0	2.21	1	0
Peripheral Nerve Diseases [description not available]	0	2.21	1	0
Peripheral Nervous System Diseases Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.	0	2.21	1	0
Adenocarcinoma Of Kidney [description not available]	0	2.25	1	0
Cancer of Kidney [description not available]	0	2.25	1	0
Carcinoma, Renal Cell A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma.	0	2.25	1	0
Kidney Neoplasms Tumors or cancers of the KIDNEY.	0	2.25	1	0
Germinoblastoma [description not available]	0	2.25	1	0
Lymphoma A general term for various neoplastic diseases of the lymphoid tissue.	0	2.25	1	0
Genetic Predisposition [description not available]	0	2.25	1	0
Rhabdomyosarcoma, Embryonal A form of RHABDOMYOSARCOMA arising primarily in the head and neck, especially the orbit, of children below the age of 10. The cells are smaller than those of other rhabdomyosarcomas and are of two basic cell types: spindle cells and round cells. This cancer is highly sensitive to chemotherapy and has a high cure rate with multi-modality therapy. (From Holland et al., Cancer Medicine, 3d ed, p2188)	0	2.25	1	0
Blood Poisoning [description not available]	0	2.31	1	0
Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.	0	2.31	1	0
Endotoxemia A condition characterized by the presence of ENDOTOXINS in the blood. On lysis, the outer cell wall of gram-negative bacteria enters the systemic circulation and initiates a pathophysiologic cascade of pro-inflammatory mediators.	0	7.31	1	0
Cancer, Embryonal [description not available]	0	2.31	1	0
Cancer of Testis [description not available]	0	2.31	1	0
Neoplasms, Germ Cell and Embryonal Neoplasms composed of primordial GERM CELLS of embryonic GONADS or of elements of the germ layers of the EMBRYO, MAMMALIAN. The concept does not refer to neoplasms located in the gonads or present in an embryo or FETUS.	0	2.31	1	0
Testicular Neoplasms Tumors or cancer of the TESTIS. Germ cell tumors (GERMINOMA) of the testis constitute 95% of all testicular neoplasms.	0	2.31	1	0
Carcinoma, Squamous Cell of Head and Neck [description not available]	0	2.31	1	0
Cancer of Head [description not available]	0	2.31	1	0
Cancer of the Tongue [description not available]	0	2.31	1	0
Squamous Cell Carcinoma of Head and Neck The most common type of head and neck carcinoma that originates from cells on the surface of the NASAL CAVITY; MOUTH; PARANASAL SINUSES, SALIVARY GLANDS, and LARYNX. Mutations in TNFRSF10B, PTEN, and ING1 genes are associated with this cancer.	0	2.31	1	0
Head and Neck Neoplasms Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)	0	2.31	1	0
Tongue Neoplasms Tumors or cancer of the TONGUE.	0	2.31	1	0
Cancer of Liver [description not available]	0	2.15	1	0
Liver Neoplasms Tumors or cancer of the LIVER.	0	2.15	1	0
Abnormalities, Autosome [description not available]	0	2.15	1	0
Cancer of Colon [description not available]	0	2.15	1	0
Colonic Neoplasms Tumors or cancer of the COLON.	0	2.15	1	0
ADPKD [description not available]	0	2.17	1	0
Polycystic Kidney, Autosomal Dominant Kidney disorders with autosomal dominant inheritance and characterized by multiple CYSTS in both KIDNEYS with progressive deterioration of renal function.	0	2.17	1	0
Carcinogenesis The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years.	0	2.17	1	0
Adenoma, Basal Cell [description not available]	0	2.17	1	0
Cell Transformation, Neoplastic Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.	0	2.17	1	0
Adenoma A benign epithelial tumor with a glandular organization.	0	2.17	1	0
HPV Infection [description not available]	0	2.17	1	0
Carcinoma, Epidermoid [description not available]	0	2.17	1	0
Cancer of Skin [description not available]	0	2.17	1	0
Carcinoma, Squamous Cell A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)	1	4.17	1	0
Skin Neoplasms Tumors or cancer of the SKIN.	0	2.17	1	0
Papillomavirus Infections Neoplasms of the skin and mucous membranes caused by papillomaviruses. They are usually benign but some have a high risk for malignant progression.	0	2.17	1	0
Idiopathic Parkinson Disease [description not available]	0	2.17	1	0
Parkinson Disease A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)	0	2.17	1	0
Lung Adenocarcinoma [description not available]	0	2.17	1	0
Cancer of Lung [description not available]	0	2.17	1	0
Adenocarcinoma of Lung A carcinoma originating in the lung and the most common lung cancer type in never-smokers. Malignant cells exhibit distinct features such as glandular epithelial, or tubular morphology. Mutations in KRAS, EGFR, BRAF, and ERBB2 genes are associated with this cancer.	0	2.17	1	0
Lung Neoplasms Tumors or cancer of the LUNG.	0	2.17	1	0
Alloxan Diabetes [description not available]	0	2.21	1	0
Asymmetric Diabetic Proximal Motor Neuropathy [description not available]	0	2.21	1	0
Diabetic Neuropathies Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325)	0	2.21	1	0
ER-Negative PR-Negative HER2-Negative Breast Cancer [description not available]	0	2.11	1	0
Triple Negative Breast Neoplasms Breast neoplasms that do not express ESTROGEN RECEPTORS; PROGESTERONE RECEPTORS; and do not overexpress the NEU RECEPTOR/HER-2 PROTO-ONCOGENE PROTEIN.	0	2.11	1	0
Benign Neoplasms, Brain [description not available]	0	2.52	2	0
Astrocytoma, Grade IV [description not available]	0	2.11	1	0
Brain Neoplasms Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.	0	2.52	2	0
Glioblastoma A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.	0	2.11	1	0
Glial Cell Tumors [description not available]	0	2.11	1	0
Arachnoidal Cerebellar Sarcoma, Circumscribed [description not available]	0	2.11	1	0
Glioma Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)	0	2.11	1	0
Medulloblastoma A malignant neoplasm that may be classified either as a glioma or as a primitive neuroectodermal tumor of childhood (see NEUROECTODERMAL TUMOR, PRIMITIVE). The tumor occurs most frequently in the first decade of life with the most typical location being the cerebellar vermis. Histologic features include a high degree of cellularity, frequent mitotic figures, and a tendency for the cells to organize into sheets or form rosettes. Medulloblastoma have a high propensity to spread throughout the craniospinal intradural axis. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2060-1)	0	2.11	1	0
Neuroblastoma A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)	0	2.11	1	0
Cancer of Prostate [description not available]	0	2.13	1	0
Prostatic Neoplasms Tumors or cancer of the PROSTATE.	0	2.13	1	0
Innate Inflammatory Response [description not available]	0	2.15	1	0
Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	0	2.15	1	0
Atrial Remodeling Long-term changes in the electrophysiological parameters and/or anatomical structures of the HEART ATRIA that result from prolonged changes in atrial rate, often associated with ATRIAL FIBRILLATION or long periods of intense EXERCISE.	0	2.15	1	0
Cardiovascular Stroke [description not available]	0	2.15	1	0
Myocardial Infarction NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).	0	2.15	1	0

lgk974

Description

Cross-References

Synonyms (57)

Research Excerpts

Treatment

Bioavailability

Dosage Studied

Roles (1)

Drug Classes (4)

Pathways (4)

Protein Targets (7)

Potency Measurements

Inhibition Measurements

Biological Processes (8)

Molecular Functions (3)

Ceullar Components (5)

Bioassays (68)

Research

Studies (54)

Market Indicators

Research Demand Index: 33.54

Study Types

Clinical Trials (2)

Trial Overview

lgk974

Description

Cross-References

Synonyms (57)

Research Excerpts

Treatment

Bioavailability

Dosage Studied

Roles (1)

Drug Classes (4)

Pathways (4)

Protein Targets (7)

Potency Measurements

Inhibition Measurements

Biological Processes (8)

Molecular Functions (3)

Ceullar Components (5)

Bioassays (68)

Research

Studies (54)

Market Indicators

Research Demand Index: 33.54

Study Types

Clinical Trials (2)

Trial Overview

Related Drugs (36)

Related Conditions (78)