sotorasib profile

sotorasib: a KRAS(G12C) inhibitor [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

sotorasib : A pyridopyrimidine that is pyrido[2,3-d]pyrimidin-2(1H)-one substituted by 4-methyl-2-(propan-2-yl)pyridin-3-yl, (2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl, fluoro and 2-fluoro-6-hydroxyphenyl groups at positions 1, 4, 6 and 7, respectively. It is approved for the treatment of patients with non-small cell lung cancer having KRAS(G12C) mutations. [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	137278711
CHEMBL ID	4535757
CHEBI ID	178199
SCHEMBL ID	20560375

Synonym
amg 510
sotorasib
CHEBI:178199 ,
6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2s)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1h)-one
amg510
lumakras
2296729-00-3
amg-510 ,
sotorasibum
S8830
AC-35168
6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-propan-2-ylpyridin-3-yl)-4-((2s)-2-methyl-4-prop-2-enoylpiperazin-1-yl)pyrido(2,3-d)pyrimidin-2-one
unii-2b2vm6uc8g
sotorasib [usan:inn]
who 11370
D77975
2252403-56-6
SCHEMBL20560375
DB15569
BS-16684
(1r)-4-((s)-4-acryloyl-2-methylpiperazin-1-yl)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(2-isopropyl-4-methylpyridin-3-yl)pyrido[2,3-d]pyrimidin-2(1h)-one
AMY16918
amg 510 pound>>amg-510
BCP30452
amg510 racemate
sotorasib [jan]
kras mutant-targeting amg 510
sotorasib [who-dd]
(1m)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(propan-2-yl)pyridin-3-yl)-4-((2s)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl)pyrido(2,3-d)pyrimidin-2(1h)-one
HY-114277
2B2VM6UC8G ,
sotorasib [usan]
6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1m)-1-(4-methyl-2-(propan-2-yl)pyridin-3-yl)-4-((2s)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl)pyrido(2,3-d)pyrimidin-2(1h)-one
CS-0081316
kras g12c inhibitor 9
sotorasib [inn]
pyrido(2,3-d)pyrimidin-2(1h)-one, 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(1-methylethyl)-3-pyridinyl)-4-((2s)-2-methyl-4-(1-oxo-2-propen-1-yl)-1-piperazinyl)-, (1r)-
pyrido(2,3-d)pyrimidin-2(1h)-one, 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(1-methylethyl)-3-pyridinyl)-4-((2s)-2-methyl-4-(1-oxo-2-propen-1-yl)-1-piperazinyl)-
(1ra)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-4-((2s)-2-methyl-4-(1-oxoprop-2-en-1-yl)piperazin-1-yl)-1-(4-methyl-2-(propan-2-yl)pyridin-3-yl)pyrido(2,3-d)pyrimidin-2(1h)-one
sotorasib [orange book]
amg510 ; amg 510; amg-510; amg510
BCP33368
nsc818433
nsc-818433
sotorasib racemate
D70074
4-((s)-4-acryloyl-2-methylpiperazin-1-yl)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(2-isopropyl-4-methylpyridin-3-yl)pyrido[2,3-d]pyrimidin-2(1h)-one ,
A930071
amg-510 racemate
pyrido[2,3-d]pyrimidin-2(1h)-one, 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-[4-methyl-2-(1-methylethyl)-3-pyridinyl]-4-[(2s)-2-methyl-4-(1-oxo-2-propen-1-yl)-1-piperazinyl]-, (1r)-
A934531
AMG-510(RACEMATE)
lumykras
6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-propan-2-ylpyridin-3-yl)-4-[(2s)-2-methyl-4-prop-2-enoylpiperazin-1-yl]pyrido[2,3-d]pyrimidin-2-one
compound (r)-38 [pmid: 31820981]
gtpl10678
2296729-00-3 (racemate)
2296729-66-1
(1s)-4-((s)-4-acryloyl-2-methylpiperazin-1-yl)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(2-isopropyl-4-methylpyridin-3-yl)pyrido[2,3-d]pyrimidin-2(1h)-one
AKOS037649138
bdbm50514402
EX-A3538
CHEMBL4535757 ,
BA172506
amg 510 racemate
BA172505
6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2s)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]-1h,2h-pyrido[2,3-d]pyrimidin-2-one
6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-[4-methyl-2-(2-propanyl)-3-pyridinyl]-4-[(2s)-2-methyl-4-(2-propenoyl)-1-piperazinyl]pyrido[2,3-d]pyrimidin-2(1h)-one
DTXSID001099260
GLXC-25372
compound (r)-38 (pmid: 31820981)
6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(propan-2-yl)pyridin-3-yl)-4-((2s)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl)pyrido(2,3-d)pyrimidin-2(1h)-one

Excerpt	Reference
"Sotorasib (Lumakras™) is a first-in-class, non-genotoxic, small molecule inhibitor of KRAS G12C developed as an anticancer therapeutic for treatment of patients that have a high unmet medical need. "	( Characterization of false positive, contaminant-driven mutagenicity in impurities associated with the sotorasib drug substance. Aiello, F; Coppi, A; Corbett, MT; Davies, R; Han, J; Ishida, K; Karmel, J; Minocherhomji, S; Monticello, TM; Parsons, AT; Wegesser, T; Xie, Y, 2022)
"Sotorasib is a first-in-class specific small molecule that irreversibly inhibits KRAS G12C."	( Editorial: Recent Approval of Sotorasib as the First Targeted Therapy for KRAS G12C-Mutated Advanced Non-Small Cell Lung Cancer (NSCLC). Parums, DV, 2022)
"Sotorasib is an oral, small molecule inhibitor of the Kirsten rat sarcoma oncogene homolog (KRAS) G12C mutant protein (KRASG12C) protein approved by the U.S."	( Impact of Sotorasib on the Pharmacokinetics and Pharmacodynamics of Metformin, a MATE1/2K Substrate, in Healthy Subjects. Houk, BE; Vuu, I; Wahlstrom, J, 2023)
"Sotorasib is a KRAS inhibitor with promising anticancer activity in phase I clinical studies. "	( Quantification of KRAS inhibitor sotorasib in mouse plasma and tissue homogenates using liquid chromatography-tandem mass spectrometry. Beijnen, JH; Loos, NHC; Retmana, IA; Schinkel, AH; Sparidans, RW, 2021)

Excerpt	Reference
"Sequential anti-programmed cell death protein 1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) followed by small targeted therapy use is associated with increased prevalence of adverse events (AEs) in NSCLC."	( Brief Report: Severe Sotorasib-Related Hepatotoxicity and Non-Liver Adverse Events Associated With Sequential Anti-Programmed Cell Death (Ligand)1 and Sotorasib Therapy in KRAS Auclin, E; Basse, C; Bigay-Game, L; Bombaron, P; Brosseau, S; Cadranel, J; Chour, A; Cortot, A; Costantini, A; Creusot, Q; Darrason, M; Decroisette, C; Denis, J; Duruisseaux, M; Fallet, V; Gaillard, CM; Girard, N; Giroux-Leprieur, E; Gounant, V; Gueçamburu, M; Lafitte, C; Lebossé, F; Mascaux, C; Meersseman, C; Odier, L; Rochand, A; Swalduz, A; Tissot, C; Wasielewski, E; Zysman, M, 2023)

Excerpt	Reference
"The management of immunosuppressors in solid organ transplantation requires pharmacological therapeutic monitoring with regular adaptation of the dosage to the residual level."	( Sotorasib associated with tacrolimus and everolimus: A significant drug interaction in lung transplant patients. Bedouch, P; Briault, A; Degano, B; Falque, L; Liaigre, L; Orhon, P; Perrier, Q; Raymond, CS; Romand, P, 2022)

Role	Description
antineoplastic agent	A substance that inhibits or prevents the proliferation of neoplasms.
[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
acrylamides	An enamide which is acrylamide or a derivative of acrylamide obtained by replacement of one or more of its hydrogens.
N-acylpiperazine
pyridopyrimidine	Any organic heterobicyclic compound consisting of a pyridine ring ortho-fused at any position to a pyrimidine ring.
monofluorobenzenes	Any member of the class of fluorobenzenes containing a mono- or poly-substituted benzene ring carrying a single fluorine substitutent.
methylpyridines	Any member of the class of pyridines that carries at least one methyl substituent.
tertiary carboxamide	A carboxamide resulting from the formal condensation of a carboxylic acid with a secondary amine; formula RC(=O)NHR(1)R(2).
tertiary amino compound	A compound formally derived from ammonia by replacing three hydrogen atoms by organyl groups.
phenols	Organic aromatic compounds having one or more hydroxy groups attached to a benzene or other arene ring.
[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]

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
GTPase KRas	Homo sapiens (human)	IC50 (µMol)	2.5269	0.0084	1.1334	5.8800	AID1559567; AID1697072; AID1729521; AID1901007
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Process	via Protein(s)	Taxonomy
MAPK cascade	GTPase KRas	Homo sapiens (human)
positive regulation of protein phosphorylation	GTPase KRas	Homo sapiens (human)
visual learning	GTPase KRas	Homo sapiens (human)
gene expression	GTPase KRas	Homo sapiens (human)
positive regulation of gene expression	GTPase KRas	Homo sapiens (human)
glial cell proliferation	GTPase KRas	Homo sapiens (human)
Rac protein signal transduction	GTPase KRas	Homo sapiens (human)
forebrain astrocyte development	GTPase KRas	Homo sapiens (human)
actin cytoskeleton organization	GTPase KRas	Homo sapiens (human)
negative regulation of epithelial cell differentiation	GTPase KRas	Homo sapiens (human)
regulation of synaptic transmission, GABAergic	GTPase KRas	Homo sapiens (human)
positive regulation of Rac protein signal transduction	GTPase KRas	Homo sapiens (human)
skeletal muscle cell differentiation	GTPase KRas	Homo sapiens (human)
negative regulation of neuron apoptotic process	GTPase KRas	Homo sapiens (human)
regulation of long-term neuronal synaptic plasticity	GTPase KRas	Homo sapiens (human)
homeostasis of number of cells within a tissue	GTPase KRas	Homo sapiens (human)
striated muscle cell differentiation	GTPase KRas	Homo sapiens (human)
neuron apoptotic process	GTPase KRas	Homo sapiens (human)
positive regulation of glial cell proliferation	GTPase KRas	Homo sapiens (human)
epithelial tube branching involved in lung morphogenesis	GTPase KRas	Homo sapiens (human)
type I pneumocyte differentiation	GTPase KRas	Homo sapiens (human)
Ras protein signal transduction	GTPase KRas	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
GTPase activity	GTPase KRas	Homo sapiens (human)
G protein activity	GTPase KRas	Homo sapiens (human)
protein binding	GTPase KRas	Homo sapiens (human)
protein-membrane adaptor activity	GTPase KRas	Homo sapiens (human)
protein-containing complex binding	GTPase KRas	Homo sapiens (human)
GDP binding	GTPase KRas	Homo sapiens (human)
GTP binding	GTPase KRas	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
Golgi membrane	GTPase KRas	Homo sapiens (human)
cytoplasm	GTPase KRas	Homo sapiens (human)
mitochondrial outer membrane	GTPase KRas	Homo sapiens (human)
endoplasmic reticulum membrane	GTPase KRas	Homo sapiens (human)
cytosol	GTPase KRas	Homo sapiens (human)
plasma membrane	GTPase KRas	Homo sapiens (human)
focal adhesion	GTPase KRas	Homo sapiens (human)
cytoplasmic side of plasma membrane	GTPase KRas	Homo sapiens (human)
membrane	GTPase KRas	Homo sapiens (human)
plasma membrane	GTPase KRas	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (80)

Assay ID	Title	Year	Journal	Article
AID1729520	Inhibition of recombinant human N-terminal polyHis-tagged KRAS isoform 2B G12C mutant (Thr2 to Cys185 residues) expressed in Escherichia coli using GTP as substrate measured after 2 hrs by GTPase-glo assay	2021	European journal of medicinal chemistry, Mar-05, Volume: 213	Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRAS
AID1729514	Antiproliferative activity against human MIA PaCa-2 cells harboring KRAS G12C mutant assessed as growth inhibition at 1 uM measured after 72 hrs by CCK8 assay relative to control	2021	European journal of medicinal chemistry, Mar-05, Volume: 213	Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRAS
AID1729519	Antiproliferative activity against human MIA PaCa-2 cells harboring KRAS G12C mutant assessed as growth inhibition measured after 72 hrs by CCK8 assay	2021	European journal of medicinal chemistry, Mar-05, Volume: 213	Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRAS
AID1769397	Cytotoxicity against human NCI-H358 cells harboring KRASG12C mutant assessed as reduction in cell viability measured after 72 hrs in presence of compound 1 by CellTiter-Glo luciferase-based ATP detection assay	2021	ACS medicinal chemistry letters, Oct-14, Volume: 12, Issue:10	KRAS Mutant Combination Therapy for the Effective Treatment of Cancer.
AID1769393	Cytotoxicity against human NCI-H23 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay	2021	ACS medicinal chemistry letters, Oct-14, Volume: 12, Issue:10	KRAS Mutant Combination Therapy for the Effective Treatment of Cancer.
AID1559594	Covalent inhibition of recombinant human His-tagged KRAS G12C/C51S/C80L/C118S mutant (1 to 169 residues) expressed in Escherichia coli assessed as enzyme-compound adduct formation by measuring ratio of Kinact/Ki after 16 to 20 hrs of overnight incubation
AID1559596	Half life of compound at 25 degree C
AID1889606	Binding affinity to KRAS (unknown origin) assessed as inhibition constant	2022	Journal of medicinal chemistry, 02-24, Volume: 65, Issue:4	Drugging the Next Undruggable KRAS Allele-Gly12Asp.
AID1729513	Antiproliferative activity against human MIA PaCa-2 cells harboring KRAS G12C mutant assessed as growth inhibition at 0.1 uM measured after 72 hrs by CCK8 assay relative to control	2021	European journal of medicinal chemistry, Mar-05, Volume: 213	Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRAS
AID1918459	Inhibition of SOS1/KRAS G12C mutant (unknown origin) protein-protein interaction	2022	Journal of medicinal chemistry, 11-10, Volume: 65, Issue:21	Fragment Optimization of Reversible Binding to the Switch II Pocket on KRAS Leads to a Potent, In Vivo Active KRAS
AID1559591	Protein binding in plasma of Sprague-Dawley rat assessed as unbound fraction at 0.25 uM by ultracentrifugation
AID1559595	Half life of compound in aqueous phosphate buffer at pH 7.4 and at 37 degree C in presence of 5 mM GSH
AID1559606	Unbound plasma concentration in athymic nude mouse xenografted with human MIAPaCa2 cells at 10 mg/kg, po qd after 8 hrs post-last dose
AID1559585	Oral bioavailability in Sprague-Dawley rat at 10 mg/kg
AID1769398	Cytotoxicity against human NCI-H23 cells harboring KRASG12C mutant assessed as reduction in cell viability measured after 72 hrs in presence of compound 1 by CellTiter-Glo luciferase-based ATP detection assay	2021	ACS medicinal chemistry letters, Oct-14, Volume: 12, Issue:10	KRAS Mutant Combination Therapy for the Effective Treatment of Cancer.
AID1559572	Permeability of compound across apical to basolateral membrane in MDCK2 cells at 10 to 50 uM incubated for 2 hrs under shaking condition by LC-MS/MS analysis
AID1559568	Antiproliferative activity against human MIAPaCa2 cells harboring KRAS G12C point mutant assessed as cell growth inhibition after 72 hrs by Celltiter-Glo luminescent cell viability assay
AID1559583	Volume of distribution at steady state in Sprague-Dawley rat at 1 mg/kg, iv or 10 mg/kg, po
AID1559592	Protein binding in plasma of Beagle dog assessed as unbound fraction at 0.25 uM by ultracentrifugation
AID1777598	Cmax in non-small-cell lung cancer/colorectal cancer patient serum at 960 mg, po	2021	ACS medicinal chemistry letters, Aug-12, Volume: 12, Issue:8	Improved Synthesis of New FDA-Approved Treatment for KRAS G12C Mutation in Non-small Cell Lung Cancer.
AID1559597	Decrease in ERK1/ERK2 phosphorylation in human MIAPaCa2 cells xenografted in athymic nude mouse at > 10 mg/kg, po administered as single dose measured after 60 to 120 mins post-treatment
AID1559582	Clearance in Sprague-Dawley rat at 1 mg/kg, iv or 10 mg/kg, po
AID1559602	Antitumor activity against human MIAPaCa2 cells harboring KRAS G12C point mutant xenografted in athymic nude mouse assessed as tumor growth inhibition at 10 mg/kg, po qd measured after 26 days relative to control
AID1559600	Time taken to achieve Cmax in tumor of athymic nude mouse xenografted with human MIAPaCa2 cells at > 10 mg/kg, po administered as single dose
AID1697073	Antiproliferative activity against human NCI-H358 cells
AID1918460	Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant incubated for 3 days by celltiter glo luminescent assay	2022	Journal of medicinal chemistry, 11-10, Volume: 65, Issue:21	Fragment Optimization of Reversible Binding to the Switch II Pocket on KRAS Leads to a Potent, In Vivo Active KRAS
AID1777599	AUC in non-small-cell lung cancer/colorectal cancer patient serum at 960 mg, po	2021	ACS medicinal chemistry letters, Aug-12, Volume: 12, Issue:8	Improved Synthesis of New FDA-Approved Treatment for KRAS G12C Mutation in Non-small Cell Lung Cancer.
AID1918457	Binding affinity to KRAS G12C mutant (unknown origin) assessed as inactivation constant incubated for 24 hrs by LC-MS analysis	2022	Journal of medicinal chemistry, 11-10, Volume: 65, Issue:21	Fragment Optimization of Reversible Binding to the Switch II Pocket on KRAS Leads to a Potent, In Vivo Active KRAS
AID1559574	Solubility of compound in FaSSIF incubated for 48 to 72 hrs under shaking conditions by LCMS analysis
AID1729526	Inhibition of KRAS G12C mutant in human NCI-H358 cells assessed as upward shift of protein band migration measured after 6 hrs by Western blot analysis	2021	European journal of medicinal chemistry, Mar-05, Volume: 213	Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRAS
AID1559589	Oral bioavailability in Beagle dog at 10 mg/kg
AID1559577	Volume of distribution at steady state in BALB/c mouse at 1 mg/kg, iv or 10 mg/kg, po
AID1559593	Protein binding in plasma of human assessed as unbound fraction at 0.25 uM by ultracentrifugation
AID1652156	Inhibition of recombinant KRAS G12C mutant (unknown origin) assessed as Kinact/Ki ratio by LC-MS analysis	2020	Journal of medicinal chemistry, 07-09, Volume: 63, Issue:13	Identification of the Clinical Development Candidate
AID1889607	Binding affinity to KRAS (unknown origin) assessed as inactivation constant	2022	Journal of medicinal chemistry, 02-24, Volume: 65, Issue:4	Drugging the Next Undruggable KRAS Allele-Gly12Asp.
AID1729516	Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as growth inhibition at 0.1 uM measured after 72 hrs by SRB assay relative to control	2021	European journal of medicinal chemistry, Mar-05, Volume: 213	Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRAS
AID1901009	Antiproliferative activity against human NCI-H23 cells harboring KRAS G12C mutant measured after 72 hrs by CCK-8 assay	2022	European journal of medicinal chemistry, Feb-15, Volume: 230	Efficient targeted oncogenic KRAS
AID1729515	Antiproliferative activity against human MIA PaCa-2 cells harboring KRAS G12C mutant assessed as growth inhibition at 10 uM measured after 72 hrs by CCK8 assay relative to control	2021	European journal of medicinal chemistry, Mar-05, Volume: 213	Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRAS
AID1559569	Antiproliferative activity against human A549 cells harboring KRAS G12S point mutant assessed as cell growth inhibition after 72 hrs by Celltiter-Glo luminescent cell viability assay
AID1559567	Inhibition of KRAS in human MIAPaca2 cells assessed as decrease in EGF-stimulated ERK1/2 phosphorylation preincubated for 2 hrs followed by EGF stimulation
AID1559578	Half life in BALB/c mouse at 1 mg/kg, iv or 10 mg/kg, po
AID1729522	Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant assessed as growth inhibition measured after 72 hrs by SRB assay	2021	European journal of medicinal chemistry, Mar-05, Volume: 213	Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRAS
AID1559584	Half life in Sprague-Dawley rat at 1 mg/kg, iv or 10 mg/kg, po
AID1769392	Cytotoxicity against human NCI-H358 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay	2021	ACS medicinal chemistry letters, Oct-14, Volume: 12, Issue:10	KRAS Mutant Combination Therapy for the Effective Treatment of Cancer.
AID1769400	Cytotoxicity against human NCI-H1373 cells harboring KRASG12C mutant assessed as reduction in cell viability measured after 72 hrs in presence of compound 1 by CellTiter-Glo luciferase-based ATP detection assay	2021	ACS medicinal chemistry letters, Oct-14, Volume: 12, Issue:10	KRAS Mutant Combination Therapy for the Effective Treatment of Cancer.
AID1559604	Antitumor activity against human MIAPaCa2 cells harboring KRAS G12C point mutant xenografted in athymic nude mouse assessed as tumor regression at 100 mg/kg, po qd measured after 26 days relative to control
AID1697072	Inhibition of KRAS G12C mutant in human NCI-H358 cells assessed as reduction in p-ERK levels
AID1559605	Antitumor activity against human MIAPaCa2 cells harboring KRAS G12C point mutant xenografted in athymic nude mouse assessed as tumor regression at >= 30 mg/kg, po qd measured after 26 days
AID1559599	Time taken to achieve Cmax in plasma of athymic nude mouse xenografted with human MIAPaCa2 cells at > 10 mg/kg, po administered as single dose
AID1559576	Clearance in BALB/c mouse at 1 mg/kg, iv or 10 mg/kg, po
AID1559575	Solubility of compound in 0.01N HCl at pH 2 incubated for 48 to 72 hrs under shaking conditions by LCMS analysis
AID1559587	Volume of distribution at steady state in Beagle dog at 1 mg/kg, iv or 10 mg/kg, po
AID1769399	Cytotoxicity against human NCI-H2122 cells harboring KRASG12C mutant assessed as reduction in cell viability measured after 72 hrs in presence of compound 1 by CellTiter-Glo luciferase-based ATP detection assay	2021	ACS medicinal chemistry letters, Oct-14, Volume: 12, Issue:10	KRAS Mutant Combination Therapy for the Effective Treatment of Cancer.
AID1559570	Intrinsic clearance in mouse cryopreserved hepatocytes assessed per 10'6 cells at 0.5 uM measured upto 60 mins by LCMS analysis
AID1559571	Intrinsic clearance in human cryopreserved hepatocytes assessed per 10'6 cells at 0.5 uM measured upto 60 mins by LCMS analysis
AID1769396	Cytotoxicity against human NCI-H1792 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay	2021	ACS medicinal chemistry letters, Oct-14, Volume: 12, Issue:10	KRAS Mutant Combination Therapy for the Effective Treatment of Cancer.
AID1729523	Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as growth inhibition measured after 72 hrs by SRB assay	2021	European journal of medicinal chemistry, Mar-05, Volume: 213	Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRAS
AID1777600	Elimination half life in non-small-cell lung cancer/colorectal cancer patient serum at 960 mg, po	2021	ACS medicinal chemistry letters, Aug-12, Volume: 12, Issue:8	Improved Synthesis of New FDA-Approved Treatment for KRAS G12C Mutation in Non-small Cell Lung Cancer.
AID1901007	Inhibition of KRAS G12C mutant (unknown origin) assessed as inhibition of SOS1-catalyzed nucleotide exchange measured by HTRF assay	2022	European journal of medicinal chemistry, Feb-15, Volume: 230	Efficient targeted oncogenic KRAS
AID1918458	Binding affinity to KRAS G12C mutant (unknown origin) assessed as inhibition constant incubated for 24 hrs by LC-MS analysis	2022	Journal of medicinal chemistry, 11-10, Volume: 65, Issue:21	Fragment Optimization of Reversible Binding to the Switch II Pocket on KRAS Leads to a Potent, In Vivo Active KRAS
AID1559588	Half life in Beagle dog at 1 mg/kg, iv or 10 mg/kg, po
AID1559579	Oral bioavailability in BALB/c mouse at 10 mg/kg
AID1729518	Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as growth inhibition at 10 uM measured after 72 hrs by SRB assay relative to control	2021	European journal of medicinal chemistry, Mar-05, Volume: 213	Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRAS
AID1901008	Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant measured after 72 hrs by CCK-8 assay	2022	European journal of medicinal chemistry, Feb-15, Volume: 230	Efficient targeted oncogenic KRAS
AID1918470	Antiproliferative activity against human NCI-H358	2022	Journal of medicinal chemistry, 11-10, Volume: 65, Issue:21	Fragment Optimization of Reversible Binding to the Switch II Pocket on KRAS Leads to a Potent, In Vivo Active KRAS
AID1769401	Cytotoxicity against human NCI-H1792 cells harboring KRASG12C mutant assessed as reduction in cell viability measured after 72 hrs in presence of compound 1 by CellTiter-Glo luciferase-based ATP detection assay	2021	ACS medicinal chemistry letters, Oct-14, Volume: 12, Issue:10	KRAS Mutant Combination Therapy for the Effective Treatment of Cancer.
AID1889608	Binding affinity to KRAS (unknown origin) assessed as ratio of inactivation constant to inhibition constant	2022	Journal of medicinal chemistry, 02-24, Volume: 65, Issue:4	Drugging the Next Undruggable KRAS Allele-Gly12Asp.
AID1729524	Antiproliferative activity against human NCI-H1975 cells harboring wild-type KRAS assessed as growth inhibition measured after 72 hrs by SRB assay	2021	European journal of medicinal chemistry, Mar-05, Volume: 213	Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRAS
AID1901010	Antiproliferative activity against human A549 cells harboring KRAS G12S mutant measured after 72 hrs by CCK-8 assay	2022	European journal of medicinal chemistry, Feb-15, Volume: 230	Efficient targeted oncogenic KRAS
AID1729525	Inhibition of KRAS G12C mutant in human NCI-H358 cells assessed as down regulation of KRAS-GTP at 1 uM measured after 24 hrs by pull down assay	2021	European journal of medicinal chemistry, Mar-05, Volume: 213	Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRAS
AID1559603	Antitumor activity against human MIAPaCa2 cells harboring KRAS G12C point mutant xenografted in athymic nude mouse assessed as tumor regression at 30 mg/kg, po qd measured after 26 days relative to control
AID1559601	Tmin in plasma of athymic nude mouse xenografted with human MIAPaCa2 cells at > 10 mg/kg, po administered as single dose
AID1729521	Inhibition of recombinant human N-terminal His-tagged KRAS (2 to 185 residues) expressed in baculovirus infected Sf9 insect cells using GTP as substrate measured after 2 hrs by GTPase-glo assay	2021	European journal of medicinal chemistry, Mar-05, Volume: 213	Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRAS
AID1559586	Clearance in Beagle dog at 1 mg/kg, iv or 10 mg/kg, po
AID1559573	Solubility of compound in PBS buffer at pH 7.4 incubated for 48 to 72 hrs under shaking conditions by LCMS analysis
AID1729517	Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as growth inhibition at 1 uM measured after 72 hrs by SRB assay relative to control	2021	European journal of medicinal chemistry, Mar-05, Volume: 213	Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRAS
AID1769394	Cytotoxicity against human NCI-H2122 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay	2021	ACS medicinal chemistry letters, Oct-14, Volume: 12, Issue:10	KRAS Mutant Combination Therapy for the Effective Treatment of Cancer.
AID1769395	Cytotoxicity against human NCI-H1373 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay	2021	ACS medicinal chemistry letters, Oct-14, Volume: 12, Issue:10	KRAS Mutant Combination Therapy for the Effective Treatment of Cancer.
AID1559590	Protein binding in plasma of BALB/c mouse assessed as unbound fraction at 0.25 uM by ultracentrifugation
AID1918456	Binding affinity to KRAS G12C mutant (unknown origin) assessed as Kinact/Ki incubated for 24 hrs by LC-MS analysis	2022	Journal of medicinal chemistry, 11-10, Volume: 65, Issue:21	Fragment Optimization of Reversible Binding to the Switch II Pocket on KRAS Leads to a Potent, In Vivo Active KRAS
[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	2 (2.56)	24.3611
2020's	76 (97.44)	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	6 (7.69%)	5.53%
Reviews	14 (17.95%)	6.00%
Case Studies	1 (1.28%)	4.05%
Observational	0 (0.00%)	0.25%
Other	57 (73.08%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Classes	Roles
chlorine chloride : A halide anion formed when chlorine picks up an electron to form an an anion.	2.41	1	halide anion; monoatomic chlorine	cofactor; Escherichia coli metabolite; human metabolite
merbromin Merbromin: A once-popular mercury containing topical antiseptic.. merbromin : An organic sodium salt that is 2,7-dibromo-4-hydroxymercurifluorescein in which the carboxy group and the phenolic hydroxy group have been deprotonated and the resulting charge is neutralised by two sodium ions.	2.41	1
metformin Metformin: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289). metformin : A member of the class of guanidines that is biguanide the carrying two methyl substituents at position 1.	3.01	2	guanidines	environmental contaminant; geroprotector; hypoglycemic agent; xenobiotic
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.	3.41	1	azaarene; mancude organic heterobicyclic parent; ortho-fused heteroarene; quinazolines
acetylcysteine N-acetyl-L-cysteine : An N-acetyl-L-amino acid that is the N-acetylated derivative of the natural amino acid L-cysteine.	2.31	1	acetylcysteine; L-cysteine derivative; N-acetyl-L-amino acid	antidote to paracetamol poisoning; antiinfective agent; antioxidant; antiviral drug; ferroptosis inhibitor; geroprotector; human metabolite; mucolytic; radical scavenger; vulnerary
2-amino-4,5,6,7-tetrahydrobenzothiazole 2-amino-4,5,6,7-tetrahydrobenzothiazole: structure in first source	2.41	1
docetaxel anhydrous Docetaxel: A semisynthetic analog of PACLITAXEL used in the treatment of locally advanced or metastatic BREAST NEOPLASMS and NON-SMALL CELL LUNG CANCER.. docetaxel anhydrous : A tetracyclic diterpenoid that is paclitaxel with the N-benzyloxycarbonyl group replaced by N-tert-butoxycarbonyl, and the acetoxy group at position 10 replaced by a hydroxy group.	2.6	1	secondary alpha-hydroxy ketone; tetracyclic diterpenoid	antimalarial; antineoplastic agent; photosensitizing agent
erlotinib hydrochloride [no description available]	2.6	1	hydrochloride; terminal acetylenic compound	antineoplastic agent; protein kinase inhibitor
tacrolimus Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.. tacrolimus (anhydrous) : A macrolide lactam containing a 23-membered lactone ring, originally isolated from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis.	7.41	1	macrolide lactam	bacterial metabolite; immunosuppressive agent
cysteine Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.. L-cysteinium : The L-enantiomer of cysteinium.. cysteine : A sulfur-containing amino acid that is propanoic acid with an amino group at position 2 and a sulfanyl group at position 3.	3.41	1	cysteinium	fundamental metabolite
everolimus [no description available]	7.41	1	cyclic acetal; cyclic ketone; ether; macrolide lactam; primary alcohol; secondary alcohol	anticoronaviral agent; antineoplastic agent; geroprotector; immunosuppressive agent; mTOR inhibitor
phosphatidylinositol 4-phosphate phosphatidylinositol 4-phosphate : A phosphatidylinositol monophosphate carrying the phosphate group at the 4-position.	2.31	1
emd1214063 tepotinib: MET inhibitor	2.41	1
piperidines Piperidines: A family of hexahydropyridines.	2.41	1
guanosine triphosphate Guanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.	2.6	1	guanosine 5'-phosphate; purine ribonucleoside 5'-triphosphate	Escherichia coli metabolite; mouse metabolite; uncoupling protein inhibitor
ARS-1620 ARS-1620: covalent S-IIP G12C inhibitor for targeting of KRAS G12C mutant tumors. ARS-1620 : A qinazoline derivative carrying chloro and fluoro substituents at positions 6 and 8 respectively, a 2-fluoro-6-hydroxyphenyl group at position 7, and a 4-(prop-2-enoyl)piperazin-1-yl group at position 4. A potent, selective, and orally bioavailable covalent KRAS-G12C inhibitor, it inhibits the protein coding gene KRAS (Kirsten rat sarcoma virus) with high potency in cells and animals.	4.84	4	quinazolines	antineoplastic agent; antiviral agent; inhibitor

Condition	Indicated	Relationship Strength	Studies	Trials
Cancer of Pancreas [description not available]	0	9.62	11	4
Pancreatic Neoplasms Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).	1	11.62	11	4
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	2.76	2	0
Benign Neoplasms [description not available]	0	9.33	15	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.	1	11.33	15	1
Cancer of Lung [description not available]	0	14.44	50	12
Lung Neoplasms Tumors or cancer of the LUNG.	1	16.44	50	12
Adverse Drug Event [description not available]	0	3.07	3	0
Drug-Related Side Effects and Adverse Reactions Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.	0	3.07	3	0
Carcinoma, Non-Small Cell Lung [description not available]	0	11.2	34	2
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.	1	13.2	34	2
Colorectal Cancer [description not available]	0	7.41	7	3
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.	1	9.41	7	3
Carcinoma, Ductal, Pancreatic [description not available]	0	2.41	1	0
Carcinoma, Pancreatic Ductal Carcinoma that arises from the PANCREATIC DUCTS. It accounts for the majority of cancers derived from the PANCREAS.	0	2.41	1	0
Lung Adenocarcinoma [description not available]	0	7.41	1	0
Chronic Kidney Failure [description not available]	0	2.41	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.	1	4.41	1	0
Kidney Failure, Chronic The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.	0	2.41	1	0
Benign Neoplasms, Brain [description not available]	0	2.6	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	2.6	1	0
Disease Exacerbation [description not available]	0	2.6	1	0
Acute Liver Injury, Drug-Induced [description not available]	0	3.3	3	0
Chemical and Drug Induced Liver Injury A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, herbal and dietary supplements and chemicals from the environment.	0	3.3	3	0
Innate Inflammatory Response [description not available]	0	9.82	9	9
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	9.82	9	9
Cancer of Colon [description not available]	0	2.21	1	0
Colonic Neoplasms Tumors or cancer of the COLON.	0	2.21	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	3.23	1	0
Local Neoplasm Recurrence [description not available]	0	2.31	1	0
Metastase [description not available]	0	2.31	1	0
Neoplasm Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.	0	2.31	1	0
Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)	0	2.31	1	0
Acute Kidney Failure [description not available]	0	2.31	1	0
Acute Kidney Injury Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.	0	2.31	1	0

sotorasib

Description

Cross-References

Synonyms (72)

Research Excerpts

Overview

Toxicity

Dosage Studied

Roles (1)

Drug Classes (8)

Protein Targets (1)

Inhibition Measurements

Biological Processes (22)

Molecular Functions (7)

Ceullar Components (9)

Bioassays (80)

Research

Studies (78)

Study Types

sotorasib

Description

Cross-References

Synonyms (72)

Research Excerpts

Overview

Toxicity

Dosage Studied

Roles (1)

Drug Classes (8)

Protein Targets (1)

Inhibition Measurements

Biological Processes (22)

Molecular Functions (7)

Ceullar Components (9)

Bioassays (80)

Research

Studies (78)

Study Types

Related Drugs (16)

Related Conditions (35)