Mobocertinib

CovInDB Drug

DB16390

Name

Mobocertinib

Molecular Formula

C32H39N7O4

Molecular Weight

585.3064 g/mol

Description

Mobocertinib is an oral kinase inhibitor targeted against EGFR and used in the treatment of NSCLC with EGFR exon 20 insertion mutations.

Status

approved, investigational

Structure

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SDF 2D SDF 3D

Indication

Mobocertinib is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.

Mechanism of action

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The epidermal growth factor receptor (EGFR) is a transmembrane receptor that regulates signaling pathways in the control of cellular proliferation. Mutations in these proteins have been associated with certain types of lung cancer, including non-small cell lung cancer (NSCLC). While the majority of EGFR mutations associated with NSCLC involve the EGFR L858R point mutation or exon 19 deletions (referred to as "classical" EGFR mutations), less common EGFR exon 20 insertion mutations carry a particularly poor prognosis and are associated with resistance to standard targeted EGFR inhibitors. Mobocertinib is an inhibitor of EGFR that irreversibly binds to and inhibits EGFR exon 20 insertion mutations at lower concentrations than wild-type EGFR proteins, exerting a pharmacologic effect on mutant variants at concentrations 1.5- to 10-fold lower than on wild-type proteins.

IUPAC Name

propan-2-yl 2-[(4-{[2-(dimethylamino)ethyl](methyl)amino}-2-methoxy-5-(prop-2-enamido)phenyl)amino]-4-(1-methyl-1H-indol-3-yl)pyrimidine-5-carboxylate

InChI

InChI=1S/C32H39N7O4/c1-9-29(40)34-24-16-25(28(42-8)17-27(24)38(6)15-14-37(4)5)35-32-33-18-22(31(41)43-20(2)3)30(36-32)23-19-39(7)26-13-11-10-12-21(23)26/h9-13,16-20H,1,14-15H2,2-8H3,(H,34,40)(H,33,35,36)

InChI Key

AZSRSNUQCUDCGG-UHFFFAOYSA-N

Canonical SMILES

COC1=C(NC2=NC=C(C(=O)OC(C)C)C(=N2)C2=CN(C)C3=C2C=CC=C3)C=C(NC(=O)C=C)C(=C1)N(C)CCN(C)C

Reference

DrugBank

Warhead

Micheal Acceptor

Target

Epidermal growth factor receptor   [ UniProt: P00533 ]

Site

CYS-797

Inhibition Mechanism

Mobocertinib (TAK-788): A Targeted Inhibitor of EGFR Exon 20 Insertion Mutants in Non-Small Cell Lung Cancer

logP

4.92

Computed by ALOGPS

logS

-4.63

Computed by ALOGPS

Heavy Atom Count

43

Computed by RDKit

Ring Count

4

Computed by RDKit

Hydrogen Bond Acceptor Count

10

Computed by RDKit

Hydrogen Bond Donor Count

2

Computed by RDKit

Rotatable Bond Count

12

Computed by RDKit

Topological Polar Surface Area

113.85 Ų

Computed by RDKit

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No similar natural compounds found for this drug.