生物活性

• 靶点

  JAK1 IC50:11nM

  JAK2 IC50:18nM

• 描述CYT387 (Momelotinib) is an ATP-competitive inhibitor of JAK1 and JAK2 with IC50s of 11 nM and 18 nM while less activity against other kinases including JAK3 (IC50 = 155 nM). MECNISIM. CYT387 inhibits proliferation of JAK2V617F mutation HEL cells as well as Ba/F3-wt and Ba/F3-JAK2V67F cells with IC50 of approximately 1400~1500 nM. Proliferation of Ba/F3-MPLW515L cell was also inhibited with IC50 = 200 nM. In human erythroleukemia (HEL) cells, CYT387 inhibits phosphorylation of STAT-5 and STAT-3 with IC50s of 400 nM and 2500 nM. Besides, CYT387 can also inhibit in vitro erythroid colony formation in polycythemia vera patients.^[1]Together with paclitaxel, CYT387-treated human ovarian HEY cells showed a significant reduced tumor burden compared to that with paclitaxel only-treated transplanted cells in mice.^[2] CYT387 could be used in the treatment of primary myelofibrosis or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (post-PV/ET MF), as well as the treatment for relapsed or refractory metastatic pancreatic ductal adenocarcinoma (in combination with capecitabine and oxaliplatin).
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  human HEL 92.1.7 cells	-	Proliferation assay	72 h	Antiproliferative activity against human HEL 92.1.7 cells expressing JAK2 V617F mutant kinase after 72 hrs by alamar blue assay, IC50=1.804 μM	19762238
  human SET2 cells	-	Proliferation assay	72 h	Antiproliferative activity against human SET2 cells expressing JAK2 V617F mutant kinase after 72 hrs by alamar blue assay, IC50=0.232 μM	19762238
  mouse BAF3 cells	-	Proliferation assay	72 h	Antiproliferative activity against mouse BAF3 cells expressing TEL-JAK2 kinase after 72 hrs by alamar blue assay	19762238

• 动物研究
  剂量	Mice: 25 mg/kg, 50 mg/kg[3] (p.o.), 100 mg/kg[4] (p.o.)
  给药途径	p.o.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02251821	Primary Myelofibrosis ... more >> Secondary Myelofibrosis Collapse <<	Phase 2	Recruiting	-	United States, Washington ... more >> Fred Hutch/University of Washington Cancer Consortium Recruiting Seattle, Washington, United States, 98109 Contact: Rachel B. Salit    206-667-1317    rsalit@fredhutch.org    Principal Investigator: Rachel B. Salit Collapse <<
  NCT02206763	EGFR Mutated EGFR TKI Naive Me... more >>tastatic NSCLC Collapse <<	Phase 1	Terminated	-	United States, California ... more >> Duarte, California, United States Palo Alto, California, United States Whittier, California, United States Collapse <<
  NCT01998828	Polycythemia Vera ... more >> Essential Thrombocythemia Collapse <<	Phase 2	Terminated	-	United States, Arizona ... more >> Scottsdale, Arizona, United States United States, California Whittier, California, United States United States, Mississippi Tupelo, Mississippi, United States United States, Missouri Saint Louis, Missouri, United States United States, Texas Houston, Texas, United States Australia, Victoria Frankston, Victoria, Australia Parkville, Victoria, Australia Canada, Ontario Toronto, Ontario, Canada Canada, Quebec Montreal, Quebec, Canada Canada Vancouver, Canada France La Tronche, France Nantes Cedex 1, France Paris, France Germany Dresden, Germany Minden, Germany Collapse <<

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