| CAS NO: | 1056634-68-4 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 5mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 250mg | 电议 |
| 500mg | 电议 |
| Molecular Weight (MW) | 414.46 |
|---|---|
| Formula | C23H22N6O2 |
| CAS No. | 1056634-68-4 (free base); |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility (In vitro) | DMSO: 74 mg/mL (178.5 mM) |
| Water: <1 mg/mL | |
| Ethanol: <1 mg/mL | |
| Solubility (In vivo) | 30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/mL |
| Synonyms | LM-1149 , CYT-11387; LM 1149 , CYT 11387; LM1149 , CYT11387; CYT-387; Momelotinib; Momelotinib free base; CYT387; CYT 387 Chemical Name: N-(cyanomethyl)-4-(2-((4-morpholinophenyl)amino)pyrimidin-4-yl)benzamide. InChi Key: ZVHNDZWQTBEVRY-UHFFFAOYSA-N InChi Code: InChI=1S/C23H22N6O2/c24-10-12-25-22(30)18-3-1-17(2-4-18)21-9-11-26-23(28-21)27-19-5-7-20(8-6-19)29-13-15-31-16-14-29/h1-9,11H,12-16H2,(H,25,30)(H,26,27,28) SMILES Code: O=C(NCC#N)C1=CC=C(C2=NC(NC3=CC=C(N4CCOCC4)C=C3)=NC=C2)C=C1 |
| In Vitro | In vitro activity: CYT387 inhibits the proliferation of parental Ba/F3 cells (Ba/F3-wt) stimulated by IL-3 with IC50 of 1400 nM. Furthermore, CYT387 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, CYT387 has been shown to inhibit erythroid colony growth in vitro from JAK2V617F-positive PV patients with similar potency with IC50 of 2μ-4 μM. A recent study shows that CYT387 inhibits PI3K/AKT and Ras/MAPK signaling induced by IL-6 and IGF-1. Moreover, CYT387 induces apoptosis as a single agent and synergizes with the conventional anti-MM therapies bortezomib and melphalan in primary multiple myeloma (MM) cells. Kinase Assay: Glutathione-S-transferase (GST)-tagged JAK kinase domains expressed in insect cells are purified before use in a peptide substrate phosphorylation assay. Assays are carried out in 384-well optiplates using an Alphascreen Protein Tyrosine Kinase P100 detection kit and a PerkinElmer Fusion Alpha instrument. 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 |
|---|---|
| In Vivo | In a murine MPN model, CYT387 normalizes white cell counts, hematocrit, spleen size, and restores physiologic levels of inflammatory cytokines. |
| Animal model | Balb/c mice are transplanted with bone marrow transduced with a JAK2V617F retrovirus. |
| Formulation & Dosage | Dissolved in NMP (120 mg/mL final; 1-methyl-2-pyrrolidinone, Chromasolv Plus). Subsequently, the CYT387/NMP mix is diluted with 0.14 M Captisol to a concentration of 6 mg/mL and further diluted with 0.1M Captisol to a final concentration of 4 mg; 50 mg daily; Oral gavage |
| References | Leukemia. 2009 Aug;23(8):1441-5; Leukemia. 2011 Dec;25(12):1891-9; Blood. 2010 Jun 24;115(25):5232-40. |
|
Effect of CYT387 on cytokine concentrations during MPN in vivo. Blood. 2010 Jun 24;115(25):5232-40. |
Efficacy of CYT387 against JAK2-dependent malignancy in vivo. Blood. 2010 Jun 24;115(25):5232-40. |
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