Momelotinib API is a small-molecule pharmaceutical active ingredient belonging to the Janus kinase (JAK) inhibitor class. Momelotinib is used in pharmaceutical development and approved therapies for myelofibrosis, a chronic myeloproliferative neoplasm associated with bone marrow fibrosis, anemia, splenomegaly and disease-related constitutional symptoms. The active pharmaceutical substance used in the approved medicine is momelotinib dihydrochloride monohydrate.
Momelotinib has the molecular formula C23H22N6O2 as the free base and a molecular weight of 414.47 g/mol. The pharmaceutical salt, momelotinib dihydrochloride monohydrate, has the molecular formula C23H22N6O2·2HCl·H2O and a molecular weight of 505.40 g/mol. The free-base CAS number is 1056634-68-4, while the dihydrochloride monohydrate salt is identified by CAS number 1841094-17-4.
Pharmacologically, momelotinib inhibits JAK1 and JAK2, including the JAK2 V617F mutant, and also inhibits activin A receptor type 1 (ACVR1/ALK2). JAK inhibition affects abnormal cytokine signaling associated with myelofibrosis, while ACVR1 inhibition can reduce hepcidin production and influence iron availability and erythropoiesis. This mechanism gives momelotinib a differentiated pharmacological profile among JAK inhibitors used in myelofibrosis.
The European Medicines Agency identifies momelotinib dihydrochloride monohydrate as the active substance of Omjjara. The approved European indication covers adults with moderate to severe anemia who have primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis and who are JAK-inhibitor naïve or have previously been treated with ruxolitinib.
The U.S. product labeling describes momelotinib dihydrochloride monohydrate as a light yellow to brown to reddish-brown solid. It is slightly soluble in water and is reported as insoluble in aqueous buffers across the pH range of 2.1 to 9. The free base is practically insoluble in water. The EMA assessment report further notes that the dihydrochloride monohydrate is a non-hygroscopic crystalline solid and that its aqueous solubility behavior is affected by disproportionation in non-acidified aqueous media.
For pharmaceutical formulation development, Momelotinib API requires appropriate control of identity, assay, related substances, residual solvents, water content, elemental impurities and other quality attributes according to the applicable API specification. Public regulatory assessment documents describe characterization of the active substance using techniques including elemental analysis, mass spectrometry, NMR, FT-IR, UV, counter-ion analysis and X-ray crystallography.
The approved finished pharmaceutical product is available as oral film-coated tablets containing 100 mg, 150 mg and 200 mg of momelotinib, with each strength expressed as momelotinib equivalent. These are finished-product strengths and should not be confused with an API assay specification.
Momelotinib API is therefore an important pharmaceutical ingredient for myelofibrosis-focused drug development, formulation research and manufacturing applications. For commercial API evaluation, analytical specifications and quality documentation should always be confirmed against the applicable batch-specific Certificate of Analysis and regulatory documentation.
| Parameter | Specification |
|---|---|
| Appearance | Light yellow to brown to reddish-brown crystalline solid |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Heavy Metals | NMT 20 ppm |
| Individual Impurity | NMT 0.5% |
| Total Impurities | ≤ 1.5% |
| Water Content | NMT 1.0% |