firmonertinib   Click here for help

GtoPdb Ligand ID: 10477

Synonyms: alflutinib (pseudo INN) | ASK120067 | AST-2818 | AST2818 | example 3 [US10072002B2] | furmonertinib | Ivesa®
Approved drug
firmonertinib is an approved drug (China (2021))
Compound class: Synthetic organic
Comment: Firmonertinib (AST2818; formerly furmonertinib) is a receptor tyrosine kinase inhibitor that targets mutant forms of the EGFR more effectively than the wild type receptor kinase, with notable potency vs. the T790M resistance mutation. Firmonertinib is the formal WHO INN. It has an irreversible binding mode. AST2818's chemical structure is claimed as example 3 in Shanghai Allist Pharmaceuticals' patent US10072002B2 [2]. Note that AST2818 is administered clinically as the mesylate.
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 13
Topological polar surface area 100.44
Molecular weight 568.25
XLogP 5.22
No. Lipinski's rules broken 2
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES C=CC(=O)Nc1cc(Nc2nccc(n2)c2cn(c3c2cccc3)C)c(nc1N(CCN(C)C)C)OCC(F)(F)F
Isomeric SMILES C=CC(=O)Nc1cc(Nc2nccc(n2)c2cn(c3c2cccc3)C)c(nc1N(CCN(C)C)C)OCC(F)(F)F
InChI InChI=1S/C28H31F3N8O2/c1-6-24(40)33-21-15-22(26(41-17-28(29,30)31)36-25(21)38(4)14-13-37(2)3)35-27-32-12-11-20(34-27)19-16-39(5)23-10-8-7-9-18(19)23/h6-12,15-16H,1,13-14,17H2,2-5H3,(H,33,40)(H,32,34,35)
InChI Key GHKOONMJXNWOIW-UHFFFAOYSA-N
Bioactivity Comments
Patent US10072002B2 does not provide IC50 or Ki values for the direct inhibition of specific kinases [2]. It reports the in vitro antiproliferative effects on cells lines that express different EGFR mutants or wild type EGFR. Results from these assays indicate that AST2818 potently inhibits growth of cell lines with activating or resistance mutations but only weakly inhibits growth of cells expressing wild type EGFR. AST2818 significantly reduces tumour volume in a xenograft model of human lung cancer H1975 cell tumours in nude mice.

In vitro antiproliferative activity of AST2818 from US10072002B2 is tabulated below:
Human cell lineEGFR status IC50
HCC827; lung cancer Exon 19 deletion; activating1.34
H1975; lung cancerL858R/T790M; resistance2.28
A431; skin cancerWild type224.2
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 Inhibition - - - 2
⤷ [2]