ch5164840 profile

CH5164840: biotin-labeled version of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ID Source	ID
PubMed CID	49784851
CHEMBL ID	1939379
SCHEMBL ID	13411826
MeSH ID	M0572039

Synonym
4-amino-18,20-dimethyl-7-thia-3,5,11,15-tetraazatricyclo[15.3.1.1(2,6)]docosa-1(20),2,4,6(22),17(21),18-hexaene-10,16-dione
bdbm50362220
CHEMBL1939379 ,
3VHD
SCHEMBL13411826
1052645-73-4
ch5164840
4-amino-18,20-dimethyl-7-thia-3,5,11,15-tetraazatricyclo[15.3.1.1~2,6~]docosa-1(21),2(22),3,5,17,19-hexaene-10,16-dione
Q27467061

Excerpt	Reference	Relevance
" Threshold plasma concentrations for tumor stasis, which are determined by multiple pharmacodynamic parameters, Emax, EC50 and tumor growth rate constant, were significantly lower in HER2-positive tumors (1."	( Assessing the impact of HER2 status on the antitumor activity of an HSP90 inhibitor in human tumor xenograft mice using pharmacokinetic-pharmacodynamic modeling. Ishigai, M; Kato, M; Nagayasu, M; Ono, N; Saitoh, R; Shibahara, N; Suda, A, 2014)	0.4

Excerpt	Reference	Relevance
" Taken together, these data indicate that CH5164840 has potent antitumor activity and is highly effective in combination with erlotinib against NSCLC tumors with EGFR overexpression and mutations."	( Enhanced antitumor activity of erlotinib in combination with the Hsp90 inhibitor CH5164840 against non-small-cell lung cancer. Aoki, Y; Fujii, T; Ishii, N; Kondoh, O; Mio, T; Ono, N; Sakata, K; Suda, A; Tsukaguchi, T; Tsukuda, T; Yamazaki, T, 2013)	0.88

Excerpt	Reference	Relevance
" CH5164840 displayed high oral bioavailability in mice (F=70."	( Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors. Fukami, TA; Hada, K; Hasegawa, K; Hayase, T; Kawasaki, K; Komiyama, S; Koyano, H; Miura, T; Ono, N; Saitoh, R; Sato, S; Shimma, N; Shiratori, Y; Suda, A; Tsukuda, T; Yamazaki, T, 2012)	1.29

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Chain A, Heat shock protein HSP 90-alpha	Homo sapiens (human)	Kd	0.0005	0.0005	0.0005	0.0005	AID977611
Chain A, Heat shock protein HSP 90-alpha	Homo sapiens (human)	Kd	0.0005	0.0005	0.0005	0.0005	AID977611
Chain A, Heat shock protein HSP 90-alpha	Homo sapiens (human)	Kd	0.0005	0.0005	0.0005	0.0005	AID977611
Heat shock protein HSP 90-alpha	Homo sapiens (human)	Kd	0.0005	0.0003	0.9488	9.8000	AID641013
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Process	via Protein(s)	Taxonomy
telomere maintenance via telomerase	Heat shock protein HSP 90-alpha	Homo sapiens (human)
neuron migration	Heat shock protein HSP 90-alpha	Homo sapiens (human)
positive regulation of protein phosphorylation	Heat shock protein HSP 90-alpha	Homo sapiens (human)
activation of innate immune response	Heat shock protein HSP 90-alpha	Homo sapiens (human)
positive regulation of defense response to virus by host	Heat shock protein HSP 90-alpha	Homo sapiens (human)
skeletal muscle contraction	Heat shock protein HSP 90-alpha	Homo sapiens (human)
mitochondrial transport	Heat shock protein HSP 90-alpha	Homo sapiens (human)
response to unfolded protein	Heat shock protein HSP 90-alpha	Homo sapiens (human)
response to heat	Heat shock protein HSP 90-alpha	Homo sapiens (human)
response to cold	Heat shock protein HSP 90-alpha	Homo sapiens (human)
response to xenobiotic stimulus	Heat shock protein HSP 90-alpha	Homo sapiens (human)
response to salt stress	Heat shock protein HSP 90-alpha	Homo sapiens (human)
positive regulation of lamellipodium assembly	Heat shock protein HSP 90-alpha	Homo sapiens (human)
cardiac muscle cell apoptotic process	Heat shock protein HSP 90-alpha	Homo sapiens (human)
regulation of protein ubiquitination	Heat shock protein HSP 90-alpha	Homo sapiens (human)
positive regulation of protein polymerization	Heat shock protein HSP 90-alpha	Homo sapiens (human)
positive regulation of interferon-beta production	Heat shock protein HSP 90-alpha	Homo sapiens (human)
regulation of protein localization	Heat shock protein HSP 90-alpha	Homo sapiens (human)
protein refolding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
response to cocaine	Heat shock protein HSP 90-alpha	Homo sapiens (human)
positive regulation of protein import into nucleus	Heat shock protein HSP 90-alpha	Homo sapiens (human)
regulation of apoptotic process	Heat shock protein HSP 90-alpha	Homo sapiens (human)
regulation of protein-containing complex assembly	Heat shock protein HSP 90-alpha	Homo sapiens (human)
protein unfolding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
response to estrogen	Heat shock protein HSP 90-alpha	Homo sapiens (human)
protein insertion into mitochondrial outer membrane	Heat shock protein HSP 90-alpha	Homo sapiens (human)
positive regulation of nitric oxide biosynthetic process	Heat shock protein HSP 90-alpha	Homo sapiens (human)
positive regulation of protein catabolic process	Heat shock protein HSP 90-alpha	Homo sapiens (human)
positive regulation of cell size	Heat shock protein HSP 90-alpha	Homo sapiens (human)
response to antibiotic	Heat shock protein HSP 90-alpha	Homo sapiens (human)
protein stabilization	Heat shock protein HSP 90-alpha	Homo sapiens (human)
chaperone-mediated protein complex assembly	Heat shock protein HSP 90-alpha	Homo sapiens (human)
positive regulation of cardiac muscle contraction	Heat shock protein HSP 90-alpha	Homo sapiens (human)
chaperone-mediated autophagy	Heat shock protein HSP 90-alpha	Homo sapiens (human)
cellular response to virus	Heat shock protein HSP 90-alpha	Homo sapiens (human)
regulation of postsynaptic membrane neurotransmitter receptor levels	Heat shock protein HSP 90-alpha	Homo sapiens (human)
positive regulation of tau-protein kinase activity	Heat shock protein HSP 90-alpha	Homo sapiens (human)
telomerase holoenzyme complex assembly	Heat shock protein HSP 90-alpha	Homo sapiens (human)
cellular response to heat	Heat shock protein HSP 90-alpha	Homo sapiens (human)
protein folding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
UTP binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
CTP binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
RNA binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
mRNA binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
protein binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
ATP binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
GTP binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
ATP hydrolysis activity	Heat shock protein HSP 90-alpha	Homo sapiens (human)
sulfonylurea receptor binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
protein phosphatase binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
MHC class II protein complex binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
nitric-oxide synthase regulator activity	Heat shock protein HSP 90-alpha	Homo sapiens (human)
TPR domain binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
ubiquitin protein ligase binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
dATP binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
identical protein binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
protein homodimerization activity	Heat shock protein HSP 90-alpha	Homo sapiens (human)
histone deacetylase binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
transmembrane transporter binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
tau protein binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
GTPase binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
Rho GDP-dissociation inhibitor binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
DNA polymerase binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
scaffold protein binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
disordered domain specific binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
ATP-dependent protein folding chaperone	Heat shock protein HSP 90-alpha	Homo sapiens (human)
protein tyrosine kinase binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
unfolded protein binding	Heat shock protein HSP 90-alpha	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
extracellular region	Heat shock protein HSP 90-alpha	Homo sapiens (human)
nucleus	Heat shock protein HSP 90-alpha	Homo sapiens (human)
nucleoplasm	Heat shock protein HSP 90-alpha	Homo sapiens (human)
cytoplasm	Heat shock protein HSP 90-alpha	Homo sapiens (human)
mitochondrion	Heat shock protein HSP 90-alpha	Homo sapiens (human)
cytosol	Heat shock protein HSP 90-alpha	Homo sapiens (human)
plasma membrane	Heat shock protein HSP 90-alpha	Homo sapiens (human)
cell surface	Heat shock protein HSP 90-alpha	Homo sapiens (human)
membrane	Heat shock protein HSP 90-alpha	Homo sapiens (human)
basolateral plasma membrane	Heat shock protein HSP 90-alpha	Homo sapiens (human)
apical plasma membrane	Heat shock protein HSP 90-alpha	Homo sapiens (human)
brush border membrane	Heat shock protein HSP 90-alpha	Homo sapiens (human)
secretory granule lumen	Heat shock protein HSP 90-alpha	Homo sapiens (human)
melanosome	Heat shock protein HSP 90-alpha	Homo sapiens (human)
neuronal cell body	Heat shock protein HSP 90-alpha	Homo sapiens (human)
lysosomal lumen	Heat shock protein HSP 90-alpha	Homo sapiens (human)
dendritic growth cone	Heat shock protein HSP 90-alpha	Homo sapiens (human)
axonal growth cone	Heat shock protein HSP 90-alpha	Homo sapiens (human)
perinuclear region of cytoplasm	Heat shock protein HSP 90-alpha	Homo sapiens (human)
collagen-containing extracellular matrix	Heat shock protein HSP 90-alpha	Homo sapiens (human)
extracellular exosome	Heat shock protein HSP 90-alpha	Homo sapiens (human)
endocytic vesicle lumen	Heat shock protein HSP 90-alpha	Homo sapiens (human)
sperm mitochondrial sheath	Heat shock protein HSP 90-alpha	Homo sapiens (human)
sperm plasma membrane	Heat shock protein HSP 90-alpha	Homo sapiens (human)
ficolin-1-rich granule lumen	Heat shock protein HSP 90-alpha	Homo sapiens (human)
protein-containing complex	Heat shock protein HSP 90-alpha	Homo sapiens (human)
plasma membrane	Heat shock protein HSP 90-alpha	Homo sapiens (human)
neuronal cell body	Heat shock protein HSP 90-alpha	Homo sapiens (human)
perinuclear region of cytoplasm	Heat shock protein HSP 90-alpha	Homo sapiens (human)
myelin sheath	Heat shock protein HSP 90-alpha	Homo sapiens (human)
cytosol	Heat shock protein HSP 90-alpha	Homo sapiens (human)
nucleus	Heat shock protein HSP 90-alpha	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (18)

Assay ID	Title	Year	Journal	Article
AID641094	Half life in athymic nu/nu mouse at 3 mg/kg, po	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID641101	Toxicity in athymic nude BALB/c mouse bearing human HCT116 cells assessed as body weight loss at 3.13 to 25 mg/kg, po administered once daily for 11 days	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID641091	Half life in athymic nu/nu mouse at 3 mg/kg, iv	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID641097	AUC (0 to infinity) in athymic nu/nu mouse at 3 mg/kg, po	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID641012	Antiproliferative activity against human HCT116 cells	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID641096	Cmax in athymic nu/nu mouse at 3 mg/kg, po	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID641014	Antiproliferative activity against human NCI-N87 cells overexpressing Her-2	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID641093	Clearance in athymic nu/nu mouse at 3 mg/kg, iv	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID641013	Binding affinity to N-terminus biotinylated human Hsp90 alpha by surface plasmon resonance assay	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID641098	Apparent oral clearance in athymic nu/nu mouse at 3 mg/kg, po	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID641095	Tmax in athymic nu/nu mouse at 3 mg/kg, po	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID641099	Oral bioavailability in athymic nu/nu mouse at 3 mg/kg	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID641016	Intrinsic clearance in human liver microsomes assessed per mg of protein at 5 uM after 60 mins	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID641092	AUC (0 to infinity) in athymic nu/nu mouse at 3 mg/kg, iv	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID641015	Solubility of the compound in fasted state simulated intestinal fluid	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID641100	Antitumor activity against human HCT116 cells xenografted in athymic nude BALB/c mouse assessed as tumor growth inhibition at 3.13 to 25 mg/kg, po administered once daily for 11 days	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID641017	Intrinsic clearance in mouse liver microsomes assessed per mg of protein at 5 uM after 60 mins	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.
AID977611	Experimentally measured binding affinity data (Kd) for protein-ligand complexes derived from PDB	2012	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2	Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 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	6 (100.00)	24.3611
2020's	0 (0.00)	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	0 (0.00%)	5.53%
Reviews	0 (0.00%)	6.00%
Case Studies	0 (0.00%)	4.05%
Observational	0 (0.00%)	0.25%
Other	6 (100.00%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Classes	Roles
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.	2.48	2	azaarene; mancude organic heterobicyclic parent; ortho-fused heteroarene; quinazolines
erlotinib hydrochloride [no description available]	2.08	1	hydrochloride; terminal acetylenic compound	antineoplastic agent; protein kinase inhibitor
lapatinib [no description available]	2.07	1	furans; organochlorine compound; organofluorine compound; quinazolines	antineoplastic agent; tyrosine kinase inhibitor

Condition	Relationship Strength	Studies
Carcinoma, Non-Small Cell Lung [description not available]	2.08	1
Cancer of Lung [description not available]	2.08	1
Carcinoma, Non-Small-Cell Lung A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.	2.08	1
Lung Neoplasms Tumors or cancer of the LUNG.	2.08	1
Benign Neoplasms [description not available]	2.49	2
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.	2.49	2
Day Blindness [description not available]	2.1	1
Chromosome-Defective Micronuclei [description not available]	2.1	1
Breast Cancer [description not available]	2.07	1
Cancer of Stomach [description not available]	2.07	1
Breast Neoplasms Tumors or cancer of the human BREAST.	2.07	1
Stomach Neoplasms Tumors or cancer of the STOMACH.	2.07	1

ch5164840

Description

Cross-References

Synonyms (9)

Research Excerpts

Pharmacokinetics

Compound-Compound Interactions

Bioavailability

Protein Targets (4)

Activation Measurements

Biological Processes (40)

Molecular Functions (28)

Ceullar Components (27)

Bioassays (18)

Research

Studies (6)

Market Indicators

Research Demand Index: 12.56

Study Types

ch5164840

Description

Cross-References

Synonyms (9)

Research Excerpts

Pharmacokinetics

Compound-Compound Interactions

Bioavailability

Protein Targets (4)

Activation Measurements

Biological Processes (40)

Molecular Functions (28)

Ceullar Components (27)

Bioassays (18)

Research

Studies (6)

Market Indicators

Research Demand Index: 12.56

Study Types

Related Drugs (3)

Related Conditions (12)