Momelotinib-d10
Modify Date: 2024-01-10 15:35:20
Momelotinib-d10 structure
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Common Name | Momelotinib-d10 | ||
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| CAS Number | 1619927-69-3 | Molecular Weight | 424.52 | |
| Density | N/A | Boiling Point | N/A | |
| Molecular Formula | C23H12D10N6O2 | Melting Point | N/A | |
| MSDS | N/A | Flash Point | N/A | |
Use of Momelotinib-d10Momelotinib-d10 (CYT387-d10) is the deuterium labeled Momelotinib (HY-10961). Momelotinib (CYT387) is an orally active and ATP-competitive inhibitor of JAK1/JAK2 with IC50a of 11 nM and 18 nM,respectively, shows much less activity against JAK3[1][2]. |
| Name | Momelotinib-d10 |
|---|
| Description | Momelotinib-d10 (CYT387-d10) is the deuterium labeled Momelotinib (HY-10961). Momelotinib (CYT387) is an orally active and ATP-competitive inhibitor of JAK1/JAK2 with IC50a of 11 nM and 18 nM,respectively, shows much less activity against JAK3[1][2]. |
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| Related Catalog | |
| Target |
JAK2:18 nM (IC50) JAK1:11 nM (IC50) |
| In Vitro | Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs[1]. Momelotinib (0, 0.5, 1, 2, 4 μM; 10-14 d) inhibits erythroid colony growth in vitro from JAK2V617F-positive PV patients with similar potency with IC50 of 2 μM-4 μM[2]. Momelotinib (0-1 μM ; 72 h) causes the inhibition of cell proliferation in cell lines constitutively activated by JAK2 or MPL signaling with IC50s of 200 nM (Ba/F3-MPLW515L cells), 1 nM (CHRF-288-11 cells) and 700 nM (Ba/F3-TEL-JAK2 cells), respectively[2]. Momelotinib (0-5 μM; 16 h) inhibits PI3K/AKT and Ras/MAPK signaling induced by IL-6 and IGF-1[3]. Momelotinib (0-5 μM; 24-48 h) induces apoptosis as a single agent and synergizes with the conventional anti-MM therapies PS-341 and L-PAM in primary multiple myeloma (MM) cells[3]. Western Blot Analysis[2] Cell Line: Human erythroleukemia (HEL) cells Concentration: For STAT5: 0, 0.2, 0.4, 0.6, 0.8, and 1.0 μM; For STAT3:0, 0.1, 0.3, 0.6, 1.25, 2.5, and 5.0 μM Incubation Time: 2 hours Result: Inhibited the phosphorylation of STAT5 and STAT3 in a dose-dependent manner. Apoptosis Analysis[3] Cell Line: Baf3-EpoR-JAK2V617F cells Concentration: 0, 0.1, 0.3, 0.6, 1.0, 1.5, 2.0, 3.0, 3.5, and 5.0 μM Incubation Time: 48 hours Result: Inhibited cell proliferation and induced cell apoptosis in trypan blue exclusion assay. |
| In Vivo | Momelotinib (25 mg/kg and 50 mg/kg; p.o.; twice daily for 83 d) is effective in a murine model of myeloproliferative neoplasms (MPNs)[3]. In a murine MPN model, Momelotinib (CYT387) normalizes white cell counts, hematocrit, spleen size, and restores physiologic levels of inflammatory cytokines[4]. Animal Model: Balb/c mice are transplanted with bone marrow transduced with a JAK2V617F retrovirus[3] Dosage: 0 mg/kg, 25 mg/kg, 50 mg/kg Administration: Oral gavage; twice daily, for 83 days; monitored weekly Result: Resulted in a rapid drop of the white cell counts was apparent in both dose cohorts as early as 6 days after initiation of treatment and a decline of the hematocrit was apparent after 20 days. Achieved complete normalization of hematocrit at a dosage of 50 mg/kg. |
| Molecular Formula | C23H12D10N6O2 |
|---|---|
| Molecular Weight | 424.52 |