pyrotinib   Click here for help

GtoPdb Ligand ID: 9662

Synonyms: Airuini® | compound 12 [PMID: 28115222] | SHR-1258 | SHR1258
Approved drug
pyrotinib is an approved drug (China (2018))
Compound class: Synthetic organic
Comment: Pyrotinib (SHR1258) is an orally administered, irreversible inhibitor of the tyrosine kinase activities of the EGFR (HER1), HER2 and HER4 [1-2]. It is claimed as example 5 in patent US20120165352 [3].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 11
Topological polar surface area 112.4
Molecular weight 582.21
XLogP 4.47
No. Lipinski's rules broken 0
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Canonical SMILES CCOc1cc2ncc(c(c2cc1NC(=O)C=CC1CCCN1C)Nc1ccc(c(c1)Cl)OCc1ccccn1)C#N
Isomeric SMILES CCOc1cc2ncc(c(c2cc1NC(=O)/C=C/[C@H]1CCCN1C)Nc1ccc(c(c1)Cl)OCc1ccccn1)C#N
InChI InChI=1S/C32H31ClN6O3/c1-3-41-30-17-27-25(16-28(30)38-31(40)12-10-24-8-6-14-39(24)2)32(21(18-34)19-36-27)37-22-9-11-29(26(33)15-22)42-20-23-7-4-5-13-35-23/h4-5,7,9-13,15-17,19,24H,3,6,8,14,20H2,1-2H3,(H,36,37)(H,38,40)/b12-10+/t24-/m1/s1
Bioactivity Comments
Preclinical studies show that pyrotinib effectively inhibits the proliferation of HER2-overexpressing cells in vitro and in vivo [1]. The cellular potency in vitro is ~40nM. Pyrotinib-induced inhibition (@ 10 μM) of a range of kinases is provided in the Supplementary data supplied for [2], data which indicates those kinases that should be considered as potential off-targets of this compound (those with inhibition > 50%)..
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
epidermal growth factor receptor Hs Inhibitor Irreversible inhibition 7.9 pIC50 - 1
pIC50 7.9 (IC50 1.3x10-8 M) [1]
erb-b2 receptor tyrosine kinase 2 Hs Inhibitor Irreversible inhibition 7.4 pIC50 - 1
pIC50 7.4 (IC50 3.8x10-8 M) [1]