|Drug class||Tyrosine kinase inhibitor|
|Main uses||Chronic myeloid leukemia which is Philadelphia chromosome-positive (Ph+ CML)|
|Side effects||Upper respiratory tract infections, musculoskeletal pain, headache, tiredness, nausea, rash, diarrhea|
|Chemical and physical data|
|Molar mass||449.84 g·mol−1|
|3D model (JSmol)|
Asciminib, sold under the brand name Scemblix, is a medication used to treat chronic myeloid leukemia which is Philadelphia chromosome-positive (Ph+ CML). It is used when other medications have failed. It is taken by mouth twice per day.
Common side effects include upper respiratory tract infections, musculoskeletal pain, headache, tiredness, nausea, rash, and diarrhea. Other side effects may include bone marrow suppression, pancreatitis, high blood pressure, allergic reactions, and heart disease. Use in pregnancy may harm the baby. It is a tyrosine kinase inhibitor specifically of the BCR::ABL1 tyrosine kinase.
Asciminib was approved for medical use in the United States in 2021 and Europe in 2022. In the United Kingdom its costs the NHS for 30 days at 40 mg twice per day £4050 as of 2022. In the United States this amount costs about 18,500 USD.
It is used at a dose of 40 mg to 200 mg twice daily, depending on the mutations present.
Common side effects are symptoms of a cold, muscle pain, joint pain, bone pain, fatigue, nausea, diarrhea, rash as well as the patient displaying abnormal blood tests.  Serious side effects of the medication include high blood pressure, low blood cell count, problems with the pancreas, and heart issues.  Side effects of the medication on the pancreas may be observed via changes in serum lipase and amylase levels. 
Mechanism of action
Asciminib is described as a "STAMP inhibitor," which means "specifically targeting the ABL myristoyl pocket." The wild-type ABL has a myristoylated N-terminus, which binds to an allosteric site, but the ABL fusion protein does not have the myristoylated domain. In the wild-type protein, when myristoylated N-terminus binds to the allosteric site, the kinase has reduced activity. Since the mutant fusion protein does not have the myristoylated N-terminus domain, it is not subject to this form of regulation, and thus the fusion protein is constitutively active. Asciminib binds to the allosteric site, resulting in an inhibition of bcr-abl activity.
Unlike other bcr-abl inhibitors, such as imatinib, asciminib does not bind to the ATP-binding site on the active site of the enzyme. Asciminib and active site bcr-abl inhibitors have non-overlapping resistance mutations. The mutations A337V and P223S overcome the inhibitory activity of asciminib, but asciminib is not affected by the notorious T315I mutation that affects most ATP-competitive active site inhibitors, except ponatinib.
Asciminib is a substrate of the CYP3A4 enzyme.  Asciminib is an inhibitor of CYP3A4, CYP2C9, and P-glycoprotein.  Asciminib reaches steady state in 3 days. The volume of distribution of Asciminib is 151 L. 
Society and culture
On 23 June 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Scemblix, intended for the treatment of adults with Philadelphia chromosome‑positive chronic myeloid leukemia in chronic phase who have previously been treated with two or more tyrosine kinase inhibitors. The applicant for this medicinal product is Novartis Europharm Limited. Asciminib was approved for medical use in the European Union in August 2022.
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- Clinical trial number NCT02081378 for "A Phase I Study of Oral ABL001 in Patients With CML or Ph+ ALL" at ClinicalTrials.gov
- Clinical trial number NCT03106779 for "Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs" at ClinicalTrials.gov