Synonyms: ABL-001 | ABL001 | compound 1 [PMID: 30137981] | Example 9 [1] | Scemblix®
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]. ![]() Ligand Activity Visualisation ChartsThese 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. ✖ |
|
Bioactivity Comments |
ABL001 has inhibitory action on cellular proliferation in vitro; GI50 1.5nM (wild type ABL1 cell line), 35nM (ABL1T315I cell line) [1]. A meeting abstract describes preclinical anti-CML action of ABL001 in combination with nilotinib (Abstract 398, ASH Annual Meeting and Exposition, San Francisco (2014)). |
Selectivity at enzymes | ||||||||||||||||||||||||||||||||||
Key to terms and symbols | Click column headers to sort | |||||||||||||||||||||||||||||||||
|