asciminib   Click here for help

GtoPdb Ligand ID: 8962

Synonyms: ABL-001 | ABL001 | compound 1 [PMID: 30137981] | Example 9 [1] | Scemblix®
Approved drug PDB Ligand
asciminib is an approved drug (FDA (2021), EMA (2022))
Compound class: Synthetic organic
Comment: Asciminib (ABL001) is a negative allosteric modulator of BCR-ABL1 [1,5,9-10], that induces the kinase to adopt an autoinhibitory, and thereby inactive, conformation [2]. The compound is the result of a structure-guided medicinal chemistry program targeting the vestigial myristoyl pocket of the ABL1 kinase. The acronym STAMP inhibitor is used to descrobe this class of compound, which specifically targets the ABL myristoyl pocket. The structure of ABL001 was disclosed at the American Society of Hematology's (ASH) 57th Annual Meeting and Exposition in Orlando, Florida (Dec., 2015)- see Abstract 1565. Mechanisms by which resistance to asciminib can develop are reported by Qiang et al. (2017) [7], including the development of T315I (confers resistance to ponatinib)-inclusive compound mutations. Combining ponatinib + asciminib has been shown to be effective against such compound mutations [3].
Asciminib-based PROTACs have been reported [11].
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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 6
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 103.37
Molecular weight 449.11
XLogP 4.3
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 OC1CCN(C1)c1ncc(cc1c1ccn[nH]1)C(=O)Nc1ccc(cc1)OC(Cl)(F)F
Isomeric SMILES O[C@@H]1CCN(C1)c1ncc(cc1c1ccn[nH]1)C(=O)Nc1ccc(cc1)OC(Cl)(F)F
InChI InChI=1S/C20H18ClF2N5O3/c21-20(22,23)31-15-3-1-13(2-4-15)26-19(30)12-9-16(17-5-7-25-27-17)18(24-10-12)28-8-6-14(29)11-28/h1-5,7,9-10,14,29H,6,8,11H2,(H,25,27)(H,26,30)/t14-/m1/s1
InChI Key VOVZXURTCKPRDQ-CQSZACIVSA-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/)
Classification Click here for help
Compound class Synthetic organic
Approved drug? Yes (FDA (2021), EMA (2022))
IUPAC Name Click here for help
N-[4-[chloro(difluoro)methoxy]phenyl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]-5-(1H-pyrazol-5-yl)pyridine-3-carboxamide
International Nonproprietary Names Click here for help
INN number INN
10267 asciminib
Synonyms Click here for help
ABL-001 | ABL001 | compound 1 [PMID: 30137981] | Example 9 [1] | Scemblix®
Database Links Click here for help
CAS Registry No. 1492952-76-7 (source: WHO INN record)
GtoPdb PubChem SID 310264743
PubChem CID 72165228
RCSB PDB Ligand AY7
Search Google for chemical match using the InChIKey VOVZXURTCKPRDQ-CQSZACIVSA-N
Search Google for chemicals with the same backbone VOVZXURTCKPRDQ
Search PubMed clinical trials asciminib
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Search PubMed titles/abstracts asciminib
UniChem Compound Search for chemical match using the InChIKey VOVZXURTCKPRDQ-CQSZACIVSA-N
UniChem Connectivity Search for chemical match using the InChIKey VOVZXURTCKPRDQ-CQSZACIVSA-N