abivertinib   Click here for help

GtoPdb Ligand ID: 10044

Synonyms: AC0010 | AC0010MA | avitinib (superceded INN) | FUJOVEE®
Compound class: Synthetic organic
Comment: Abivertinib (AC0010) is an orally active, irreversible EGFR inhibitor (third generation) that selectively targets mutated EGFRs, and which was designed to overcome T790M-induced resistance in tumours [2,4]. It also inhibits BTK, thus offering extended clinical utility [3]. We show the structure for the free base form of the compound. The maleate salt formulation is known as STI-5656.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 7
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 98.41
Molecular weight 487.21
XLogP 4.44
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES C=CC(=O)Nc1cccc(c1)Oc1nc(Nc2ccc(c(c2)F)N2CCN(CC2)C)nc2c1cc[nH]2
Isomeric SMILES C=CC(=O)Nc1cccc(c1)Oc1nc(Nc2ccc(c(c2)F)N2CCN(CC2)C)nc2c1cc[nH]2
InChI InChI=1S/C26H26FN7O2/c1-3-23(35)29-17-5-4-6-19(15-17)36-25-20-9-10-28-24(20)31-26(32-25)30-18-7-8-22(21(27)16-18)34-13-11-33(2)12-14-34/h3-10,15-16H,1,11-14H2,2H3,(H,29,35)(H2,28,30,31,32)
InChI Key UOFYSRZSLXWIQB-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Clinical efficacy of AC0010 as an anti-cancer candidate is being evaluated in a number of clinical trials. Phase 1 results in NSCLC were published in mid 2018 [1]. The most advanced trial is a Phase 3 study that is designed to compare AC0010 and chemotherapy (pemetrexed/cisplatin) in patients with advance NSCLC whose disease has progressed following prior EGFR inhibitor therapy (NCT03058094).
COVID-19: Abivertinib maleate (STI-5656) was evaluated for clinical efficacy in hospitalised COVID-19 patients. This trial was assessing the utility of exploiting the BTK-mediated immunomodulatory action of abivertinib, that inhibits production of key pro-inflammatory cytokine production, including IL-1β, IL-6 and TNFα, all of which are associated with cytokine release syndrome/cytokine storm, poor outcomes and disease progression in hospitalised COVID-19 patients.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03058094 A Study Comparing AC0010 and Chemotherapy in Patients With Advanced NSCLC Who Have Progressed Following Prior EGFR TKI Phase 3 Interventional Hangzhou ACEA Pharmaceutical Research Co., Ltd.
NCT04440007 Study of the Efficacy and Safety of STI-5656 (Abivertinib Maleate) in Subjects Hospitalized With COVID-19 Phase 2 Interventional Sorrento Therapeutics, Inc.
NCT04528667 Study of the Safety and Efficacy of STI-5656 (Abivertinib Maleate) in Subjects Hospitalized Due to COVID-19 Phase 2 Interventional Sorrento Therapeutics, Inc.
NCT02330367 Safety, Pharmacokinetic and Preliminary Efficacy Study of AC0010 in Patients With EGFR T790M Positive NSCLC Phase 1/Phase 2 Interventional Hangzhou ACEA Pharmaceutical Research Co., Ltd. 4