poziotinib   Click here for help

GtoPdb Ligand ID: 7903

Synonyms: HM781-36B | NOV120101
Compound class: Synthetic organic
Comment: Poziotinib is an orally bioavailable, clinically active, quinazoline-based pan epidermal growth factor receptor (EGFR or HER) inhibitor with antineoplastic activity [1-2]. It is a potent inhibitor of the most common EGFR and HER2 exon 20 insertion mutants that are predominantly activating in nature, and resistant to exisitng reversible and irreversible EGFR tyrosine kinase inhibitors [3-4].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 7
Topological polar surface area 76.58
Molecular weight 490.1
XLogP 4.47
No. Lipinski's rules broken 0
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Canonical SMILES C=CC(=O)N1CCC(CC1)Oc1cc2c(ncnc2cc1OC)Nc1ccc(c(c1F)Cl)Cl
Isomeric SMILES C=CC(=O)N1CCC(CC1)Oc1cc2c(ncnc2cc1OC)Nc1ccc(c(c1F)Cl)Cl
InChI InChI=1S/C23H21Cl2FN4O3/c1-3-20(31)30-8-6-13(7-9-30)33-19-10-14-17(11-18(19)32-2)27-12-28-23(14)29-16-5-4-15(24)21(25)22(16)26/h3-5,10-13H,1,6-9H2,2H3,(H,27,28,29)
1. Cha MY, Lee KO, Kim M, Song JY, Lee KH, Park J, Chae YJ, Kim YH, Suh KH, Lee GS et al.. (2012)
Antitumor activity of HM781-36B, a highly effective pan-HER inhibitor in erlotinib-resistant NSCLC and other EGFR-dependent cancer models.
Int J Cancer, 130 (10): 2445-54. [PMID:21732342]
2. Nam HJ, Kim HP, Yoon YK, Hur HS, Song SH, Kim MS, Lee GS, Han SW, Im SA, Kim TY et al.. (2011)
Antitumor activity of HM781-36B, an irreversible Pan-HER inhibitor, alone or in combination with cytotoxic chemotherapeutic agents in gastric cancer.
Cancer Lett, 302 (2): 155-65. [PMID:21306821]
3. Robichaux JP, Elamin YY, Tan Z, Carter BW, Zhang S, Liu S, Li S, Chen T, Poteete A, Estrada-Bernal A et al.. (2018)
Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer.
Nat Med, 24 (5): 638-646. [PMID:29686424]
4. Vyse S, Huang PH. (2019)
Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer.
Signal Transduct Target Ther, 4: 5. [PMID:30854234]