生物活性

• 描述Gastrointestinal stromal tumors (GIST) are the largest group of mesenchymal tumors in the intestinal tract. Over 80% of GIST harbors mutations in the c-KIT cell surface transmembrane receptor tyrosine kinase. Mutations in the platelet-derived growth factor receptor α (PDGFRα) gene accounts for 5 - 10% GIST^[1]. BLU-285 is a small molecule kinase inhibitor that shows potent inhibitory activity against PDGFRα D842V mutant in vitro with an IC50 value of 0.5 nM. It inhibits the autophosphorylation of PDGFRα D842V in the cellular setting with an IC50 value of 30 nM. BLU-285 also potently inhibits the analogous KIT mutation, D816V in KIT Exon 17, with an IC50 value of 0.5 nM. In cellular assays, BLU-285 potently inhibits KIT D816 mutants D816V (HMC1.2 cells), D816Y (P815 cells), and KIT Exon 17 mutant N822K (Kasumi cells) with IC50 values of 3 nM, 22 nM, and 40 nM, respectively. In a D816Y-driven xenograft model, BLU-285 (30 mg/kg, once daily) resulted in >90% tumor suppression^[2].

• 动物研究
  剂量	Mice: 0.3 mg/kg - 30 mg/kg[1] (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
  NCT03465722	GIST	Phase 3	Recruiting	April 2023	-
  NCT03731260	Indolent Systemic Mastocytosis... more >> Smoldering Systemic Mastocytosis Collapse <<	Phase 2	Not yet recruiting	November 2023	-
  NCT02508532	Gastrointestinal Stromal Tumor... more >>s (GIST) Other Relapsed or Refractory Solid Tumors Collapse <<	Phase 1	Recruiting	May 2019	United States, California ... more >> Sarcoma Oncology Center Recruiting Santa Monica, California, United States, 90403 United States, Florida Sylvester Comprehensive Cancer Center Recruiting Miami, Florida, United States, 33136 United States, Massachusetts Dana Farber Cancer Institute Recruiting Boston, Massachusetts, United States, 02215 United States, New York Memorial Sloan Kettering Cancer Center Recruiting New York, New York, United States, 10065 United States, Oregon Oregon Health and Science University Recruiting Portland, Oregon, United States, 97239 United States, Pennsylvania Fox Chase Cancer Center Recruiting Philadelphia, Pennsylvania, United States, 19111 United States, Texas MD Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Belgium Leuven Cancer Institute University Hospitals Leuven Recruiting Leuven, Belgium, 3000 France Centre Leon Berard Recruiting Lyon, France, 69008 Institut Gustave Roussy Recruiting Paris, France, 94805 Germany University of Duisburg-Essen Recruiting Essen, Germany, 45122 Italy Fondazione IRCCS - Istituto Nazinale dei Tumori Recruiting Milan, Italy, 20133 Korea, Republic of Asan Medical Center Recruiting Seoul, Korea, Republic of, 05505 Netherlands Erasmus MC Cancer Institute Recruiting Rotterdam, Netherlands, 3015 Poland Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie w Warszawie Recruiting Warsaw, Poland, 02-781 Spain Vall d' Hebron Institute of Oncology (VHIO) Recruiting Barcelona, Spain, 08305 United Kingdom Royal Marsden Hospital Recruiting London, United Kingdom, SW3 6JJ Collapse <<

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• 参考文献

• [1] Schneider-Stock R. BLU-285-the breakthrough in treatment of patients with aggressive systemic mastocytosis and gastrointestinal stromal tumor. Ann Transl Med. 2018 Jun;6(11):232. doi: 10.21037/atm.2018.05.21. PMID: 30023395; PMCID: PMC6036000.

  [2] BLU-285, the first selective inhibitor of PDGFRα D842V and KIT Exon 17 mutants