Sotorasib

Drug information

CovInDB Drug
DB15569
Name
Sotorasib
Molecular Formula
C30H30F2N6O3
Molecular Weight
560.2347 g/mol
Description
Sotorasib is an experimental KRAS inhibitor being investigated for the treatment of KRAS G12C mutant non small cell lung cancer, colorectal cancer, and appendix cancer.
Status
approved, investigational
Structure
2D structure
  Warhead   Similar Compounds
Indication
Sotorasib is indicated in the treatment of KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) in adults who have received at least one prior systemic therapy.
Mechanism of action

Normally GTP binds to KRAS, activating the protein and promoting effectors to the MAP kinase pathway.GTP is hydrolyzed to GDP, and KRAS is inactivated.KRAS G12C mutations impair hydrolysis of GTP, leaving it in the active form. Sotorasib binds to the cysteine residue in KRAS G12C mutations, holding the protein in its inactive form.The cysteine residue that sotorasib targets is not present in the wild type KRAS, which prevents off-target effects.This mutation is present in 13% of non small cell lung cancer, 3% of colorectal and appendix cancer, and 1-3% of solid tumors.

IUPAC Name
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
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
InChI Key
NXQKSXLFSAEQCZ-SFHVURJKSA-N
Canonical SMILES
CC(C)C1=NC=CC(C)=C1N1C(=O)N=C(N2CCN(C[C@@H]2C)C(=O)C=C)C2=CC(F)=C(N=C12)C1=C(O)C=CC=C1F
Reference
DrugBank



Covalent Inhibition


Warhead
Micheal Acceptor
Target

GTPase KRas   [ UniProt: P01116 ]

Site
CYS-12
Inhibition Mechanism

Discovery of a Covalent Inhibitor of KRAS(G12C) (AMG 510) for the Treatment of Solid Tumors.




3D Structure

  Show Warhead


Calculated Properties

logP

3.6

Computed by ALOGPS

logS

-4.48

Computed by ALOGPS

Heavy Atom Count

41

Computed by RDKit

Ring Count

5

Computed by RDKit

Hydrogen Bond Acceptor Count

8

Computed by RDKit

Hydrogen Bond Donor Count

1

Computed by RDKit

Rotatable Bond Count

5

Computed by RDKit

Topological Polar Surface Area

104.45 Å2

Computed by RDKit




Similar compounds in Virtual Screening library

  Download

ZC2750545

Similarity Score: 1.00

ZC2751309

Similarity Score: 1.00

ZC3498404

Similarity Score: 0.80

ZC3405852

Similarity Score: 0.69

ZC3053833

Similarity Score: 0.60

ZC2750893

Similarity Score: 0.52



Similar Natural compounds

No similar natural compounds found for this drug.