1056636-07-7
1056636-07-7 structure
- Name: Momelotinib Mesylate
- Chemical Name: CYT387 Mesylate
- CAS Number: 1056636-07-7
- Molecular Formula: C24H26N6O5S
- Molecular Weight: 510.569
- Catalog: Research Areas Cancer
- Create Date: 2018-03-28 12:22:10
- Modify Date: 2024-01-12 23:10:56
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Momelotinib Mesylate (CYT387 Mesylate) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, appr 10-fold selectivity versus JAK3.
| Name | CYT387 Mesylate |
|---|---|
| Synonyms | CYT387 (Mesylate) |
| Description | Momelotinib Mesylate (CYT387 Mesylate) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, appr 10-fold selectivity versus JAK3. |
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| Related Catalog | |
| Target |
JAK1:11 nM (IC50) JAK2:18 nM (IC50) JAK3:155 nM (IC50) |
| In Vitro | Momelotinib Mesylate is an inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, appr 10-fold selectivity versus JAK3. Momelotinib inhibits the proliferation of parental Ba/F3 cells (Ba/F3-wt) stimulated by IL-3 with IC50 of 1400 nM. Furthermore, Momelotinib also causes the inhibition of cell proliferation in cell lines constitutively activated by JAK2 or MPL signaling, including Ba/F3-MPLW515L cells, CHRF-288-11 cells and Ba/F3-TEL-JAK2 cells with IC50 of 200 nM, 1 nM and 700 nM, respectively. In addition, Momelotinib has been shown to inhibit erythroid colony growth in vitro from JAK2V617F-positive PV patients with similar potency with IC50 of 2 μM-4 μM[1]. Momelotinib inhibits PI3K/AKT and Ras/MAPK signaling induced by IL-6 and IGF-1. Moreover, Momelotinib induces apoptosis as a single agent and synergizes with the conventional anti-MM therapies bortezomib and melphalan in primary multiple myeloma (MM) cells[2]. |
| In Vivo | In a murine MPN model, Momelotinib normalizes white cell counts, hematocrit, spleen size, and restores physiologic levels of inflammatory cytokines[3]. |
| Cell Assay | Ba/F3 cells expressing JAK2V617F (Ba/F3-JAK2V617F) and MPLW515L (Ba/F3-MPLW515L) mutants, as well as CHRF-288-11 (JAK2T875N) and CMK (JAK3A572V) cells are used. The TEL/JAK2 and TEL/JAK3 fusions are generated and introduced into Ba/F3 murine cells. The TEL/JAK2- or TEL/JAK3-transfected cells are cultured in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal calf serum (FCS). Ba/F3 wild-type cells are cultured in RPMI containing 10% FCS supplemented with 5 ng/mL murine IL-3. Proliferation is measured using the Alamar Blue assay after incubating for 72 hours at 37°C with 5% CO2[1]. |
| Animal Admin | Mice[3] On day 32 after bone marrow transplantation (when all mice exhibit severe leukocytosis and erythrocytosis), mice are assigned to 3 groups such that each group had equivalent average body weight and blood counts. Momelotinib is dissolved in NMP (120 mg/mL final; 1-methyl-2-pyrrolidinone). Subsequently, the Momelotinib/NMP mix is diluted with 0.14 M Captisol to a concentration of 6 mg/mL and further diluted with 0.1 M Captisol to a final concentration of 4 mg/mL. All 3 groups of mice (n=12 per group) are administered Momelotinib by oral gavage twice daily at 10- to 12-hour intervals from day 34 after bone marrow transplantation to day 82 (end of experiment). Mice receive NMP/Captisol without Momelotinib (0 mg/kg group), 25 mg/kg Momelotinib, or 50 mg/kg Momelotinib. At day 82 after bone marrow transplantation, all mice are euthanized for analysis except for 2 mice each from the 50 mg/kg and 25 mg/kg groups, which are taken off Momelotinib treatment and followed for 45 additional days. For assessment of the effects of Momelotinib on normal blood counts, naive Balb/c mice are administered vehicle control, or 50 mg/kg, or 100 mg/kg Momelotinib in an identical fashion for the bone marrow transplant experimental mouse cohort. Peripheral blood is drawn at day 14, 28, 42, and 56 and levels of red cells, white cells, reticulocytes, granulocytes, lymphocytes, and monocytes are analyzed[3]. |
| References |
| Molecular Formula | C24H26N6O5S |
|---|---|
| Molecular Weight | 510.569 |
| Storage condition | 2-8℃ |