Details of the Drug

General Information of Drug (ID: DMLSV74)

Drug Name

Sotorasib

Synonyms

AMG-510; AMG510; AMG-510 racemate; 2252403-56-6; AMG 510; Kras G12C inhibitor 9; 2296729-00-3; UNII-2B2VM6UC8G; 2B2VM6UC8G; CHEMBL4535757; 2296729-00-3 (racemate); 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; 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; Sotorasib [INN]; 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; AMG510 racemate; Sotorasib [USAN]; AMG-510(racemate); Kras mutant-targeting AMG 510; SCHEMBL20560375; GTPL10678; AMG 510 pound>>AMG-510; AMY16918; BCP30452; BCP33368; EX-A3538; BDBM50514402; NSC818433; s8830; WHO 11370; DB15569; NSC-818433; BS-16684; HY-114277; CS-0081316; compound (R)-38 [PMID: 31820981]; AMG510 ; AMG 510; AMG-510; AMG510; (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; (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; 2296729-66-1; 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)-

Indication

Disease Entry	ICD 11	Status	REF
Non-small-cell lung cancer	2C25	Approved	[1]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

560.6

Logarithm of the Partition Coefficient (xlogp)

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 65.3 mgh/L [2]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 7.50 mg/L [2]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2 h [2]
Clearance: The clearance of drug is 26.2 L/h [3]
Elimination: Sotorasib is 74% eliminated in the feces and 6% eliminated in the urine [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 5.5 +/- 1.8 hours [2]
Metabolism: The drug is metabolized via the CYP3As [3]
Vd: The volume of distribution (Vd) of drug is 211 L [3]

Chemical Identifiers

Formula: C30H30F2N6O3
IUPAC Name: 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
Canonical SMILES: C[C@H]1CN(CCN1C2=NC(=O)N(C3=NC(=C(C=C32)F)C4=C(C=CC=C4F)O)C5=C(C=CN=C5C(C)C)C)C(=O)C=C
InChI: InChI=1S/C30H30F2N6O3/c1-6-23(40)36-12-13-37(18(5)15-36)28-19-14-21(32)26(24-20(31)8-7-9-22(24)39)34-29(19)38(30(41)35-28)27-17(4)10-11-33-25(27)16(2)3/h6-11,14,16,18,39H,1,12-13,15H2,2-5H3/t18-/m0/s1
InChIKey: NXQKSXLFSAEQCZ-SFHVURJKSA-N

Cross-matching ID

PubChem CID: 137278711
CAS Number: 2252403-56-6
DrugBank ID: DB15569
TTD ID: D0R7LD

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
KRAS G12C mutant (KRAS G12C)	TT3LH46	RASK_HUMAN	Inhibitor	[4]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Protein Interaction/Cellular Processes	[5]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Post-Translational Modifications	[5]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Drug Response	[5]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Post-Translational Modifications	[5]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Post-Translational Modifications	[5]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Post-Translational Modifications	[5]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

References

1	FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 214665.
2	KRAS(G12C) Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med. 2020 Sep 24;383(13):1207-1217. doi: 10.1056/NEJMoa1917239. Epub 2020 Sep 20.
3	FDA Approved Drug Products: Lumakras (Sotorasib) Oral Tablet
4	Clinical pipeline report, company report or official report of Amgen.
5	The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019 Nov;575(7781):217-223. doi: 10.1038/s41586-019-1694-1. Epub 2019 Oct 30.