生物活性

• 靶点

  c-Kit IC50:10nM

  PDGFRα IC50:40nM

  FLT3 IC50:81nM

• 描述c-KIT is a tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. c-KIT is a proto-oncogene. Activating or gain of function mutations in c-KIT have been identified in a variety of tumors^[3]. Amuvatinib, also termed MP470, is an inhibitor of various mutant c-KIT kinases. The inhibitory IC50s of MP470 against c-KIT(D816V), c-KIT(D816H), c-KIT(V560G), c-KIT(V654A) were 0.95 μM, 0.01 μM, 0.034 μM and 0.127 μM, respectively. The IC50 for MP470 on OVCAR-3 cells proliferation was 0.9 μM^[3]. According to another report, the IC50 for MP470 on prostate cancer LNCaP and PC-3 cells were ~4 μM and 8 μM, respectively, when incubated for 4 days. Flow cytometric analysis revealed that 48h treatment of MP470 to LNCaP cells at the concentration of 10 μM induced 28% of apoptosis^[4]. In a HT-29 xenograft model, MP470 was i.p. administrated at the doses of 10 or 20 mg/kg at the schedule of 5 times a week for 2 weeks. Both doses significantly inhibited tumor growth. In an A549 xenograft model, MP470 was orally administrated at the doses of 50, 100, or 200 mg/kg, also 5 times a week for 2 weeks. All three doses exhibited anti-tumor activity^[3]. In another LNCaP xenograft model, MP470 was i.p. dosed at 50 mg/kg daily for 24 days. This dose in combination with Erlotinib had a marked effect with tumor growth inhibition of 45-65%, while both drugs were of modest activity as a single agent^[4].

• 动物研究
  剂量	Mice: 50 mg/kg[1] (i.p.)
  给药途径	i.p.

• 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
  NCT00504205	Lymphoma Unsp... more >>ecified Adult Solid Tumor, Protocol Specific Collapse <<	Not Applicable	Terminated(Withdrawn as trial ... more >>was never activated by SuperGen) Collapse <<	-	United States, Arizona ... more >> Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea Scottsdale, Arizona, United States, 85258-4512 United States, Texas South Texas Accelerated Research Therapeutics San Antonio, Texas, United States, 78229 Collapse <<
  NCT00894894	Solid Tumors	Phase 1	Completed	-	United States, Arizona ... more >> Translation Genomics Research Institute (TGen)/Scottsdale Clin.Researc Scottsdale, Arizona, United States, 85258 United States, Texas So. Texas Accelerated Research Therapeutics-START San Antonio, Texas, United States, 78229 Collapse <<
  NCT00881166	Malignant Disease	Phase 1	Completed	-	United States, Arizona ... more >> Premiere Oncology Scottsdale, Arizona, United States, 85258 United States, California Premiere Oncology Santa Monica, California, United States, 90404 United States, Texas Audie Murphy Veterans Memorial Hospital (VA) San Antonio, Texas, United States, 78229 CTRC at the UT Health Science Center at San Antonio San Antonio, Texas, United States, 78229 South Texas Accelerated Research Therapy (START) San Antonio, Texas, United States, 78229 Collapse <<

• 更多
• 参考文献

• [1] Qi W, Cooke LS, et al. MP470, a novel receptor tyrosine kinase inhibitor, in combination with Erlotinib inhibits the HER family/PI3K/Akt pathway and tumor growth in prostate cancer. BMC Cancer. 2009 May 11;9:142.

  [2] Mahadevan D, Cooke L, et al. A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors. Oncogene. 2007 Jun 7;26(27):3909-19.

  [3] PHARMACEUTICAL FORMULATIONS COMPRISING SALTS OF A PROTEIN KINASE INHIBITOR AND METHODS OF USING SAME

  [4] Qi W, Cooke LS, Stejskal A, Riley C, Croce KD, Saldanha JW, Bearss D, Mahadevan D. MP470, a novel receptor tyrosine kinase inhibitor, in combination with Erlotinib inhibits the HER family/PI3K/Akt pathway and tumor growth in prostate cancer. BMC Cancer. 2009 May 11;9:142.