Momelotinib-CYT387-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEMomelotinibCat. No.: HY-10961CAS No.: 1056634-68-4Synonyms: CYT387分式: CHNO分量: 414.46作靶点: JAK; Autophagy作通路: Epigenetics; JAK/STAT Signaling; Stem Cell/Wnt; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C

2、1 month溶解性数据体外实验 DMSO : 40 mg/mL (96.51 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.4128 mL 12.0639 mL 24.1278 mL5 mM 0.4826 mL 2.4128 mL 4.8256 mL10 mM 0.2413 mL 1.2064 mL 2.4128 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验 请根据您的实验动物和给药式选择适当

3、的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.03 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 Momelotinib (CYT387

4、)是ATP 竞争性的 JAK1/JAK2 抑制剂，IC50 值分别为 11 nM/18 nM，是对 JAK3 选择性的 10 倍左右。IC50 & Target JAK1 JAK2 JAK311 nM (IC50) 18 nM (IC50) 155 nM (IC50)体外研究 Momelotinib (CYT387) inhibits the proliferation of parental Ba/F3 cells (Ba/F3-wt) stimulated by IL-3 withIC50 of 1400 nM. Furthermore, Momelotinib (CYT387) also

5、 causes the inhibition of cell proliferation in celllines constitutively activated by JAK2 or MPL signaling, including Ba/F3-MPLW515L cells, CHRF-288-11cells and Ba/F3-TEL-JAK2 cells with IC50 of 200 nM, 1 nM and 700 nM, respectively. In addition,Momelotinib (CYT387) has been shown to inhibit erythr

6、oid colony growth in vitro from JAK2V617F-positivePV patients with similar potency with IC50 of 2 M-4 M 1. Momelotinib (CYT387) inhibits PI3K/AKT andRas/MAPK signaling induced by IL-6 and IGF-1. Moreover, Momelotinib (CYT387) induces apoptosis as asingle agent and synergizes with the conventional an

7、ti-MM therapies PS-341 and L-PAM in primary multiplemyeloma (MM) cells 2.体内研究 In a murine MPN model, Momelotinib (CYT387) normalizes white cell counts, hematocrit, spleen size, andrestores physiologic levels of inflammatory cytokines 3.PROTOCOLKinase Assay 1 Glutathione-S-transferase (GST)-tagged JA

8、K kinase domains expressed in insect cells are purified beforeuse in a peptide substrate phosphorylation assay. Assays are carried out in 384-well optiplates using anAlphascreen Protein Tyrosine Kinase P100 detection kit and a PerkinElmer Fusion Alpha instrument.MCE has not independently confirmed t

9、he accuracy of these methods. They are for reference only.Cell Assay 1 Ba/F3 cells expressing JAK2V617F (Ba/F3-JAK2V617F) and MPLW515L (Ba/F3-MPLW515L) mutants, aswell as CHRF-288-11 (JAK2T875N) and CMK (JAK3A572V) cells are used. The TEL/JAK2 and TEL/JAK3fusions are generated and introduced into Ba

10、/F3 murine cells. The TEL/JAK2- or TEL/JAK3-transfected cellsare cultured in Dulbeccos modified Eagles medium (DMEM) containing 10% fetal calf serum (FCS). Ba/F3wild-type cells are cultured in RPMI containing 10% FCS supplemented with 5 ng/mL murine IL-3.Proliferation is measured using the Alamar Bl

11、ue assay after incubating for 72 hours at 37C with 5% CO2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal On day 32 after bone marrow transplantation (when all mice exhibit severe leukocytosis and erythrocytosis),Administration 3 mice are assigne

12、d to 3 groups such that each group had equivalent average body weight and blood counts.Momelotinib (CYT387) is dissolved in NMP (120 mg/mL final; 1-methyl-2-pyrrolidinone). Subsequently, theCYT387/NMP mix is diluted with 0.14 M Captisol to a concentration of 6 mg/mL and further diluted with 0.1MCapt

13、isol to a final concentration of 4 mg/mL. All 3 groups of mice (n=12 per group) are administeredMomelotinib (CYT387) by oral gavage twice daily at 10- to 12-hour intervals from day 34 after bone marrowtransplantation to day 82 (end of experiment). Mice receive NMP/Captisol without Momelotinib (CYT38

14、7) (0mg/kg group), 25 mg/kg Momelotinib (CYT387), or 50 mg/kg Momelotinib (CYT387). At day 82 after bone2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEmarrow transplantation, all mice are euthanized for analysis except for 2 mice each from the 50 mg/kg and25 mg/kg groups, which are taken off Momel

15、otinib (CYT387) treatment and followed for 45 additional days.For assessment of the effects of CYT387 on normal blood counts, naive Balb/c mice are administeredvehicle control, 50 mg/kg, or 100 mg/kg Momelotinib (CYT387) in an identical fashion as described for thebone marrow transplant experimental

16、 mouse cohort. Peripheral blood is drawn at day 14, 28, 42, and 56 andlevels of red cells, white cells, reticulocytes, granulocytes, lymphocytes, and monocytes are analyzed 3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Cancer Cell. 2018

17、Sep 10;34(3):439-452.e6. Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. J Pineal Res. 2019 Apr;66(3):e12552. Leukemia. 2012 Oct;26(10):2233-44. Cell Syst. 2018 Apr 25;6(4):424-443.e7.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Pardanani A, et al. CYT387, a selective JA

18、K1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using celllines and primary cells from polycythemia vera patients. Leukemia, 2009, 23(8), 1441-1445.2. Monaghan KA, et al. The novel JAK inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and inducesapoptosis in phenotypically diverse myeloma cells. Leukemi