olverembatinib   Click here for help

GtoPdb Ligand ID: 10630

Synonyms: compound 10a [PMID: 23301703] | GZD-824 | GZD824 | HQP-1351 | HQP1351
Approved drug PDB Ligand Immunopharmacology Ligand
olverembatinib is an approved drug (China (2021))
Compound class: Synthetic organic
Comment: Olverembatinib (HQP1351; formerly GZD824) is a novel third-generation, orally bioavailable kinase inhibitor with activity against a broad spectrum of Bcr-Abl mutants including the T315I resistance mutation [3-4]. The chemical structure for GZD824 is identical to that submitted to the WHO for the INN olverembatinib. GZD824's structure and use was first claimed in a patent from the Guangzhou Institute of Biomedicine and Health [5], but it is now being progressed by Ascentage Pharma and HealthQuest Pharma.
SARS-CoV-2: Olverembatinib has been reported to inhibit human PBM cytokine release (in vitro) as induced by the SARS-CoV-2 omicron variant [1].
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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

olverembatinib is commercially available from our sponsors

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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Click here for structure editor
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 6
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 77.15
Molecular weight 532.22
XLogP 5.95
No. Lipinski's rules broken 1

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 CN1CCN(CC1)Cc1ccc(cc1C(F)(F)F)NC(=O)c1ccc(c(c1)C#Cc1cnc2c(c1)cn[nH]2)C
Isomeric SMILES CN1CCN(CC1)Cc1ccc(cc1C(F)(F)F)NC(=O)c1ccc(c(c1)C#Cc1cnc2c(c1)cn[nH]2)C
InChI InChI=1S/C29H27F3N6O/c1-19-3-5-22(14-21(19)6-4-20-13-24-17-34-36-27(24)33-16-20)28(39)35-25-8-7-23(26(15-25)29(30,31)32)18-38-11-9-37(2)10-12-38/h3,5,7-8,13-17H,9-12,18H2,1-2H3,(H,35,39)(H,33,34,36)
InChI Key TZKBVRDEOITLRB-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/)
References
1. Chan M, Holland EC, Gujral TS. (2022)
Olverembatinib inhibits SARS-CoV-2-Omicron variant-mediated cytokine release in human peripheral blood mononuclear cells.
EMBO Mol Med, 14 (6): e15919. [PMID:35579119]
2. Dhillon S. (2022)
Olverembatinib: First Approval.
Drugs, 82 (4): 469-475. [PMID:35195876]
3. Liu X, Wang G, Yan X, Qiu H, Min P, Wu M, Tang C, Zhang F, Tang Q, Zhu S et al.. (2019)
Preclinical development of HQP1351, a multikinase inhibitor targeting a broad spectrum of mutant KIT kinases, for the treatment of imatinib-resistant gastrointestinal stromal tumors.
Cell Biosci, 9: 88. [PMID:31673329]
4. Ren X, Pan X, Zhang Z, Wang D, Lu X, Li Y, Wen D, Long H, Luo J, Feng Y et al.. (2013)
Identification of GZD824 as an orally bioavailable inhibitor that targets phosphorylated and nonphosphorylated breakpoint cluster region-Abelson (Bcr-Abl) kinase and overcomes clinically acquired mutation-induced resistance against imatinib.
J Med Chem, 56 (3): 879-94. [PMID:23301703]
5. Wang D, Pei D, Zhang Z, Shen M, Luo K, Feng Y. (2012)
Heterocyclic alkynyl benzene compounds and medical compositions and uses thereof.
Patent number: WO-2012000304-A1. Assignee: Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences. Priority date: 01/07/2010. Publication date: 05/01/2012.