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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. ✖ |
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Summary of Clinical Use  |
| Asciminib (ABL001) was progressed to Phase 3 clinical evalution in patients with chronic myelogenous leukemia (CML) who had previously received treatment with ≥2 tyrosine kinase inhibitors in the ASCEMBL trial. Click here to link to ClinicalTrials.gov's full list of ABL001 trials. The FDA granted asciminib Fast Track designation, and in 2020 the EMA granted orphan drug designation for the treatment of CML. In the UK asciminib is available for compassionate use, on a named-patient basis. Perliminary data suggested that asciminib, was more effective than bosutinib (a second-generation kinase inhibitor that is commonly used in third-line CML treatment) in head-to-head phase 3 study NCT03106779 [8]. In February 2021, Novartis announced that the FDA had granted asciminib Breakthrough Therapy designations for previously treated, chronic phase Ph+ CML, and for chronic phase Ph+ CML with the T315I mutation. In October 2021, the FDA issued full approval for the same patient groups that were included by the Breakthrough Therapy designations. |
| Clinical Trials | |||||
| Clinical Trial ID | Title | Type | Source | Comment | References |
| NCT02081378 | A Phase I Study of Oral ABL001 in Patients With CML or Ph+ ALL | Phase 1 Interventional | Novartis | 4 | |
| NCT03106779 | Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs | Phase 3 Interventional | Novartis | ASCEMBL trial: in October 2020 Novartis announced that primary analysis of data showed that asciminib had met its primary endpoint in CML; the primary endpoint being statistically significant superiority in major molecular response rate at 24 weeks for asciminib compared to bosutinib. Results were published in August 2021. | 8 |
| Pharmacokinetics |
| Organ function impairment |
| In a small sample of patients, treatment with therapeutic doses of asciminib had minimal effect on platelet function [6]. This is in contrast to other nonspecific ATP-competitive BCR-ABL inhibitors, particulaly ponatinib and dasatinib, that are recognised as causing platelet dysfunction. |
