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Compound Detail

CHEMBL4535757

SOTORASIB
💊 Approved Drug
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💊 Approved Drug
C=CC(=O)N1CCN(c2nc(=O)n(-c3c(C)ccnc3C(C)C)c3nc(-c4c(O)cccc4F)c(F)cc23)[C@@H](C)C1

Basic Information

ChEMBL ID CHEMBL4535757
Name SOTORASIB
Phase Approved
Structure Type MOL
InChI Key NXQKSXLFSAEQCZ-SFHVURJKSA-N
Therapeutic ✓ Yes

Known Names

AMG-510 AMG510 Kras g12c inhibitor 9 Kras mutant-targeting amg 510 Lumakras Lumykras Sotorasib
11
Targets
38
Activities
3
Assay Types
29
PK Parameters
20
Publications
7
Known Names
7
Indications
1
Mechanisms

Molecular Properties

560.6
MW (Da)
4.48
ALogP
8
HBA
1
HBD
104.5
PSA (Ų)
0.36
QED
1
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2021
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

First in Class Chemical Probe
USAN Stem -rasib
USAN Year 2021

Extended Properties

Molecular Formula C30H30F2N6O3
MW 560.61
Aromatic Rings 4
Heavy Atoms 41
NP-Likeness -0.59

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
GTPase KRas inhibitor INHIBITOR GTPase KRas

Indications

Carcinoma, Non-Small-Cell Lung Neoplasms Colorectal Neoplasms Lung Neoplasms Ovarian Neoplasms Liver Diseases Pancreatic Neoplasms

ATC Classification

L01XX73
sotorasib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 33 meas. best 9.0
Ki 3 meas. best 4.91
EC50 2 meas. best 8.22

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
NCI-H358
CHEMBL614135
IC50 9.0 8.1988 1.0 8
SW837
CHEMBL1075596
IC50 8.7 8.4233 2.0 3
MIA PaCa-2
CHEMBL614725
IC50 8.3 7.8271 5.0 7
NCI-H358
CHEMBL614135
EC50 8.22 8.205 6.0 2
GTPase KRas
CHEMBL2189121
IC50 8.02 7.58 9.7 4
SOS1-KRAS
CHEMBL5465393
IC50 7.8 7.8 15.8 1
Unchecked
CHEMBL612545
IC50 7.17 6.535 68.0 2
NCI-H2122
CHEMBL1075533
IC50 7.04 6.66 90.5 2
NCI-H23
CHEMBL614997
IC50 6.95 6.385 111.5 2
NCI-H1373
CHEMBL4296389
IC50 6.45 6.45 355.7 1
NCI-H1792
CHEMBL1075525
IC50 5.52 5.52 3000.0 1
GTPase KRas
CHEMBL2189121
Ki 4.91 4.49 12200.0 2
A549
CHEMBL392
IC50 4.44 4.37 36500.0 2
Unchecked
CHEMBL612545
Ki 4.07 4.07 86000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 65300.0 ng.hr.mL-1 Homo sapiens
AUC 311.0 ng.hr.mL-1 Mus musculus
AUC 312.0 ng.hr.mL-1 Mus musculus
AUC 9438.0 ng.hr.mL-1 Mus musculus
AUC 9451.0 ng.hr.mL-1 Mus musculus
CL 26.67 mL.min-1.kg-1 Mus musculus
CL 56.67 mL.min-1.kg-1 Rattus norvegicus
CL 36.67 mL.min-1.kg-1 Canis lupus familiaris
CL 36.0 mL.min-1.g-1 Homo sapiens
CL 1.833 mL.min-1.kg-1 Mus musculus
Cmax 13378.28 nM Homo sapiens
Cmax 1539.39 nM Mus musculus
Cmax 17557.66 nM Mus musculus
F 22.0 % Mus musculus
F 2.8 % Rattus norvegicus
F 0.34 % Canis lupus familiaris
Fu 0.06 - Mus musculus
Fu 0.05 - Rattus norvegicus
Fu 0.17 - Canis lupus familiaris
Fu 0.09 - Homo sapiens
T1/2 0.5 hr Mus musculus
T1/2 0.5 hr Rattus norvegicus
T1/2 0.4 hr Canis lupus familiaris
T1/2 3.333 hr -
T1/2 1576800.0 hr -
T1/2 5.5 hr Homo sapiens
T1/2 0.252 hr Mus musculus
T1/2 3.96 hr Mus musculus
Tmax 0.25 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
NCI-H358 IC50 = 1.0 nM 9.0 Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C muta... 37395055
NCI-H358 IC50 = 1.0 nM 9.0 Antiproliferative activity against human NCI-H358 cells incubated for 6 days in ... 38316747
SW837 IC50 = 2.0 nM 8.7 Antiproliferative activity against human SW837 cells incubated for 6 days in pre... 38316747
NCI-H358 IC50 = 3.0 nM 8.52 Cytotoxicity against human NCI-H358 cells harboring KRASG12C mutant assessed as ... 34676026
SW837 IC50 = 3.0 nM 8.52 Antiproliferative activity against human SW837 cells incubated for 6 days in pre... 38316747
NCI-H358 IC50 = 4.0 nM 8.4 Antiproliferative activity against human NCI-H358 cells incubated for 6 days in ... 38316747
MIA PaCa-2 IC50 = 5.0 nM 8.3 Antiproliferative activity against human MIAPaCa2 cells harboring KRAS G12C poin... 31820981
NCI-H358 EC50 = 6.0 nM 8.22 Antiproliferative activity against human NCI-H358 36300829
MIA PaCa-2 IC50 = 6.0 nM 8.22 Antiproliferative activity against human MIA PaCa-2 cells incubated for 6 days i... 38316747
NCI-H358 EC50 = 6.4 nM 8.19 Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C muta... 36300829
NCI-H358 IC50 = 8.4 nM 8.08 Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C muta... 35007863
SW837 IC50 = 9.0 nM 8.05 Antiproliferative activity against human SW837 cells incubated for 6 days by CCK... 38316747
GTPase KRas IC50 = 9.66 nM 8.02 Inhibition of KRAS G12C mutant (unknown origin) assessed as inhibition of SOS1-c... 35007863
NCI-H358 IC50 = 10.0 nM 8.0 Antiproliferative activity against human NCI-H358 cells incubated for 6 days by ... 38316747
NCI-H358 IC50 = 12.0 nM 7.92 Antiproliferative activity against human NCI-H358 cells expressing KRAS G12C mut... 37852032
MIA PaCa-2 IC50 = 13.0 nM 7.89 Antiproliferative activity against human MIA PaCa-2 cells incubated for 6 days i... 38316747
SOS1-KRAS IC50 = 15.8 nM 7.8 Inhibition of SOS1/KRAS G12C mutant (unknown origin) protein-protein interaction 36300829
MIA PaCa-2 IC50 = 18.0 nM 7.75 Antiproliferative activity against human MIA PaCa-2 cells expressing KRAS G12C m... 37852032
MIA PaCa-2 IC50 = 22.0 nM 7.66 Antiproliferative activity against human MIA PaCa-2 cells harboring KRAS G12C mu... 36621179
GTPase KRas IC50 = 24.5 nM 7.61 HTRF Assay: NCI-H358 cells expressing KRAS G12C mutant protein were cultured in ... -

Literature References

Data from ChEMBL 36 via Core Engine