sotorasib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
Ras protein inhibitors	5461	2296729-00-3

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: sotorasib lumakras AMG510	Sotorasib is an inhibitor of KRASG12C, a tumor-restricted, mutant-oncogenic form of the RAS GTPase, KRAS. Sotorasib forms an irreversible, covalent bond with the unique cysteine of KRASG12C, locking the protein in an inactive state that prevents downstream signaling without affecting wild-type KRAS. Sotorasib blocked KRAS signaling, inhibited cell growth, and promoted apoptosis only in KRAS G12C tumor cell lines. Sotorasib inhibited KRASG12C in vitro and in vivo with minimal detectable off-target activity. In mouse tumor xenograft models sotorasib-treatment led to tumor regressions and prolonged survival and was associated with anti-tumor immunity in KRAS G12C models. Molecular weight: 559.62 Formula: C31H31F2N5O3 CLOGP: 5.90 LIPINSKI: 1 HAC: 9 HDO: 1 TPSA: 98.99 ALOGS: -4.48 ROTB: 3 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

sotorasib
lumakras
AMG510

Sotorasib is an inhibitor of KRASG12C, a tumor-restricted, mutant-oncogenic form of the RAS GTPase, KRAS. Sotorasib forms an irreversible, covalent bond with the unique cysteine of KRASG12C, locking the protein in an inactive state that prevents downstream signaling without affecting wild-type KRAS. Sotorasib blocked KRAS signaling, inhibited cell growth, and promoted apoptosis only in KRAS G12C tumor cell lines. Sotorasib inhibited KRASG12C in vitro and in vivo with minimal detectable off-target activity. In mouse tumor xenograft models sotorasib-treatment led to tumor regressions and prolonged survival and was associated with anti-tumor immunity in KRAS G12C models.

Molecular weight: 559.62
Formula: C31H31F2N5O3
CLOGP: 5.90
LIPINSKI: 1
HAC: 9
HDO: 1
TPSA: 98.99
ALOGS: -4.48
ROTB: 3

Status: ONP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

None

ADMET properties:

Property	Value	Reference
S (Water solubility)	0.03 mg/mL	Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Bocci G, Oprea TI, Benet LZ

Approvals:

Date	Agency	Company
Jan. 6, 2022	EMA	Amgen Europe BV
May 28, 2021	FDA	AMGEN INC
Jan. 20, 2022	PMDA	AMGEN K.K.

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Non-small cell lung cancer	109.44	58.19	20	537	3575	63484890
Diarrhoea	86.81	58.19	61	496	715305	62773160
Non-small cell lung cancer metastatic	64.99	58.19	10	547	627	63487838
Death	59.43	58.19	38	519	374343	63114122

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Non-small cell lung cancer	244.37	46.33	44	535	3896	34952456
Non-small cell lung cancer metastatic	72.33	46.33	12	567	638	34955714
Death	63.84	46.33	52	527	397997	34558355

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Non-small cell lung cancer	246.72	58.15	45	842	6315	79737186
Disease progression	150.01	58.15	61	826	184301	79559200
Death	90.22	58.15	63	824	566451	79177050
Diarrhoea	79.58	58.15	70	817	880419	78863082
Hepatic cytolysis	64.38	58.15	20	867	27131	79716370

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01XX73	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS OTHER ANTINEOPLASTIC AGENTS Other antineoplastic agents
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D000074322	Antineoplastic Agents, Immunological
MeSH PA	D000082082	Immune Checkpoint Inhibitors
CHEBI has role	CHEBI:35610	antineoplastic agents

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer	indication	254637007	DOID:3908

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
120MG	LUMAKRAS	AMGEN INC	N214665	May 28, 2021	RX	TABLET	ORAL	11236091	May 20, 2040	TREATMENT OF ADULT PATIENTS WITH KRAS G12C-MUTATED LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC), AS DETERMINED BY AN FDA-APPROVED TEST, WHO HAVE RECEIVED AT LEAST ONE PRIOR SYSTEMIC THERAPY
320MG	LUMAKRAS	AMGEN INC	N214665	Jan. 20, 2023	RX	TABLET	ORAL	11236091	May 20, 2040	TREATMENT OF ADULT PATIENTS WITH KRAS G12C-MUTATED LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC), AS DETERMINED BY AN FDA-APPROVED TEST, WHO HAVE RECEIVED AT LEAST ONE PRIOR SYSTEMIC THERAPY
120MG	LUMAKRAS	AMGEN INC	N214665	May 28, 2021	RX	TABLET	ORAL	11426404	Sept. 15, 2040	TREATMENT OF ADULT PATIENTS WITH KRAS G12C-MUTATED LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC), AS DETERMINED BY AN FDA-APPROVED TEST, WHO HAVE RECEIVED AT LEAST ONE PRIOR SYSTEMIC THERAPY
320MG	LUMAKRAS	AMGEN INC	N214665	Jan. 20, 2023	RX	TABLET	ORAL	11426404	Sept. 15, 2040	TREATMENT OF ADULT PATIENTS WITH KRAS G12C-MUTATED LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC), AS DETERMINED BY AN FDA-APPROVED TEST, WHO HAVE RECEIVED AT LEAST ONE PRIOR SYSTEMIC THERAPY

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
120MG	LUMAKRAS	AMGEN INC	N214665	May 28, 2021	RX	TABLET	ORAL	May 28, 2026	NEW CHEMICAL ENTITY
320MG	LUMAKRAS	AMGEN INC	N214665	Jan. 20, 2023	RX	TABLET	ORAL	May 28, 2026	NEW CHEMICAL ENTITY
120MG	LUMAKRAS	AMGEN INC	N214665	May 28, 2021	RX	TABLET	ORAL	May 28, 2028	TREATMENT OF ADULT PATIENTS WITH KRAS G12C-MUTATED LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC), AS DETERMINED BY AN FDA-APPROVED TEST, WHO HAVE RECEIVED AT LEAST ONE PRIOR SYSTEMIC THERAPY
320MG	LUMAKRAS	AMGEN INC	N214665	Jan. 20, 2023	RX	TABLET	ORAL	May 28, 2028	TREATMENT OF ADULT PATIENTS WITH KRAS G12C-MUTATED LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC), AS DETERMINED BY AN FDA-APPROVED TEST, WHO HAVE RECEIVED AT LEAST ONE PRIOR SYSTEMIC THERAPY

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
GTPase KRas	Enzyme	P01116	RASK_HUMAN	INHIBITOR	IC50	7.03		DRUG LABEL	DRUG LABEL

External reference:

ID	Source
D12055	KEGG_DRUG
2B2VM6UC8G	UNII
C5418250	UMLSCUI
CHEBI:178199	CHEBI
CHEMBL4535757	ChEMBL_ID
137278711	PUBCHEM_CID
DB15569	DRUGBANK_ID
11370	INN_ID
10678	IUPHAR_LIGAND_ID
018747	NDDF
1162482008	SNOMEDCT_US
1162509004	SNOMEDCT_US
4040545	VANDF
2550714	RXNORM
347100	MMSL
39561	MMSL
d09751	MMSL
C000706028	MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
LUMAKRAS	HUMAN PRESCRIPTION DRUG LABEL	1	55513-488	TABLET, COATED	120 mg	ORAL	NDA	30 sections
LUMAKRAS	HUMAN PRESCRIPTION DRUG LABEL	1	55513-488	TABLET, COATED	120 mg	ORAL	NDA	30 sections
LUMAKRAS	HUMAN PRESCRIPTION DRUG LABEL	1	55513-488	TABLET, COATED	120 mg	ORAL	NDA	30 sections
LUMAKRAS	HUMAN PRESCRIPTION DRUG LABEL	1	55513-504	TABLET, COATED	320 mg	ORAL	NDA	30 sections