生物活性

• 描述The Hedgehog (Hh) pathway plays an important role in embryonic development and adult tissue maintenance via the regulation of cell differentiation and proliferation. Smoothened (Smo), a member of the GPCR superfamily, belongs to class F (Frizzled family) and is the main transducer of the Hh signaling pathway. BMS-833923 (XL 139) is an inhibitor of Smoothened with potential antineoplastic activity. Esophageal adenocarcinoma (EAC) cell lines OE19 and OE33 treated with 10 μM and 25 μM BMS-833923 showed 50% and 100% cell death, and caspase-3 was activated in 25 μM BMS-833923-treated group. Hh targeted gene Gli1 in the nuclear fraction was significantly decreased in both cell lines treated with 10 μM BMS-833923 compared to untreated cells^[3]. BMS-833923 (30 mg/kg) monotherapy for 7 days in nu/nu mice xenograft model of cholangiocarcinoma resulted in a reduction of tumor volume (60% ± 23%) but the most pronounced size reduction could be seen in the gemcitabine (40 mg/kg)/BMS-833923 combination group (32% ± 5%)^[4].

• 动物研究
  剂量	Mice: 15 mg/kg[3] (p.o.) Fish: 40 mg/kg[4] (i.p.)
  给药途径	p.o., 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
  NCT00884546	Advanced Cancer, Various, NOS	Phase 1	Completed	-	United States, California ... more >> City Of Hope National Medical Center Duarte, California, United States, 91010 Moores Ucsd Cancer Center La Jolla, California, United States, 92093 Local Institution Los Angeles, California, United States, 90048 United States, Maryland The Sidney Kimmel Comprehensive Cancer Center Baltimore, Maryland, United States, 21231 United States, Michigan Local Institution Detroit, Michigan, United States, 48201 United States, New Jersey John Theurer Cancer Center Hackensack, New Jersey, United States, 07601 United States, Texas Oncology Consultants, Pa Houston, Texas, United States, 77024 Cancer Therapy And Research Center San Antonio, Texas, United States, 78229 Collapse <<
  NCT00927875	Small Cell Lung Carcinoma	Phase 1	Completed	-	United States, Michigan ... more >> Karmanos Cancer Institute Detroit, Michigan, United States, 48201 Australia, Victoria Local Institution East Bentleigh, Victoria, Australia, 3165 Canada, Alberta Local Institution Edmonton, Alberta, Canada, T6G 1Z2 Canada, Ontario Local Institution Ottawa, Ontario, Canada, K1H 8L6 France Local Institution Villejuif Cedex, France, 94800 Ireland Local Institution Dublin, Ireland Collapse <<
  NCT01218477	Leukemia	Phase 1 Phase 2	Completed	-	United States, California ... more >> University Of California Medical Center San Francisco, California, United States, 94143 United States, Maryland Sidney Kimmel Cancer Center At Johns Hopkins Baltimore, Maryland, United States, 21287 United States, Texas Ut M.D. Anderson Cancer Center Houston, Texas, United States, 77030 Canada, Ontario Local Institution Hamilton, Ontario, Canada, L8N 3Z5 Local Institution Toronto, Ontario, Canada, M5G 2M9 Finland Local Institution Helsinki, Finland, 00290 France Local Institution Bordeaux, France, 33076 Local Institution Poitiers Cedex, France, 86021 Germany Local Institution Frankfurt/main, Germany, 60590 Italy Local Institution Bologna, Italy, 40138 Local Institution Orbassano(To), Italy, 10043 United Kingdom Local Institution Glasgow, United Kingdom, G12 0YN Collapse <<

• 更多
• 参考文献

• [1] Wilkinson SE, Furic L, et al. Hedgehog signaling is active in human prostate cancer stroma and regulates proliferation and differentiation of adjacent epithelium. Prostate. 2013 Dec;73(16):1810-23.

  [2] Zaidi AH, Komatsu Y, et al. Smoothened inhibition leads to decreased proliferation and induces apoptosis in esophageal adenocarcinoma cells. Cancer Invest. 2013 Aug;31(7):480-9.

  [3] Zaidi AH, Komatsu Y, Kelly LA, Malhotra U, Rotoloni C, Kosovec JE, Zahoor H, Makielski R, Bhatt A, Hoppo T, Jobe BA. Smoothened inhibition leads to decreased proliferation and induces apoptosis in esophageal adenocarcinoma cells. Cancer Invest. 2013 Aug;31(7):480-9. doi: 10.3109/07357907.2013.820317. PMID: 23915072.

  [4] Riedlinger D, Bahra M, Boas-Knoop S, Lippert S, Bradtmöller M, Guse K, Seehofer D, Bova R, Sauer IM, Neuhaus P, Koch A, Kamphues C. Hedgehog pathway as a potential treatment target in human cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 2014 Aug;21(8):607-15. doi: 10.1002/jhbp.107. Epub 2014 Apr 15. PMID: 24733827.