生物活性

• 描述INCB-057643 is a BET inhibitor with oral bioavailability in preclinical models of hematologic malignancies. It inhibited the binding of BRD2/BRD3/BRD4 to an acetylated histone H4 peptide in the low nanomole range with selectivity against other bromodomain containing proteins^[1]. INCB057643 exhibited anti-proliferation against androgen-dependent prostate cancer VCaP and LNCaP cells with GI50 values ≤100 nM, as well as androgen-independent DU145 and PC3 with GI50 values ≥500 nM, respectively. Also it inhibited the proliferation of 22Rv1 cells expressing androgen-independent AR splice variants with GI50 value ranging in 150-250 nM. Oral administration of INCB057643 at dose of 3mg/kg resulted significant inhibition of tumor growth (T/C%: 42 and 45%, respectively) without weight loss caused by toxicity^[2]. The proliferation of human AML, DLBCL, and multiple myeloma cell lines inhibited by INCB-057643 could be observed with a corresponding decrease in MYC protein levels, G1 arrest and a concentration-dependently increased apoptosis. Also, treatment with INCB057643 led to repression of the LPS-stimulated production of cytokines IL-6, IL-10 and MIP-1α in human and mouse whole blood^[1].

• 动物研究
  剂量	Mice: 3 mg/kg[3] (p.o., BID)
  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
  NCT02959437	Solid Tumors ... more >>Advanced Malignancies Metastatic Cancer Collapse <<	Phase 1 Phase 2	Active, not recruiting	October 2021	United States, California ... more >> City of Hope National Medical Center Duarte, California, United States, 91010 University of California San Diego La Jolla, California, United States, 92093 United States, Illinois The University of Chicago Chicago, Illinois, United States, 60637 United States, Pennsylvania University of Pennsylvania Health System Philadelphia, Pennsylvania, United States, 19014 United States, Tennessee Sarah Cannon Nashville, Tennessee, United States, 37203 Vanderbilt-Ingram Cancer Center Nashville, Tennessee, United States, 37232 United States, Texas MD Anderson Cancer Center Houston, Texas, United States, 77030 United States, Washington University of Washington Seattle, Washington, United States, 98109 Spain Vall D Hebron Univ Barcelona, Spain, 08035 Univ De Navarra Pamplona, Spain, 31008 United Kingdom University College London Hospitals (Uclh) London, United Kingdom, W1t7ha Churchill Hospital Oxford, United Kingdom, Ox37le Collapse <<
  NCT02711137	Solid Tumors	Phase 1 Phase 2	Active, not recruiting	December 2018	United States, Alabama ... more >> University of Alabama Birmingham, Alabama, United States, 35294-3300 United States, California University of California La Jolla, California, United States, 92093 United States, Colorado Sarah Cannon Research Institute at Health One Denver, Colorado, United States, 80218 United States, Connecticut Yale University New Haven, Connecticut, United States, 06510 United States, Florida Sylvester Comprehensive Cancer Center Miami, Florida, United States, 33136 Hematology - Oncology Associates of Treasure Coast Port Saint Lucie, Florida, United States, 34952 United States, Michigan University of Michigan Ann Arbor, Michigan, United States, 48109 United States, Minnesota University of Minnesota Minneapolis, Minnesota, United States, 55455 United States, Missouri Washington University Saint Louis, Missouri, United States, 63110 United States, New York University of Rochester, Wilmot Cancer Center Rochester, New York, United States, 14642 United States, North Carolina University of North Carolina at Chapel Hill Chapel Hill, North Carolina, United States, 27599 Wake Forest Baptist Health Winston-Salem, North Carolina, United States, 27157 United States, Texas Oncology Consultants, P.A. Houston, Texas, United States, 77030 The Methodist Hospital Houston, Texas, United States, 77030 United States, Utah Huntsman Cancer Institute Salt Lake City, Utah, United States, 84112 United States, Washington MultiCare Institute for Research and Innovation Tacoma, Washington, United States, 98405 Belgium Institut Jules Bordet, Clinical Trial Conduct Unit Brussels, Belgium, B-1000 France HÔPITAL SAINT-LOUIS, Service Hématologie Adultes Paris, France, 75010 Collapse <<

• 参考文献

• [1] Matthew C. S, Thomas M, et al. Preclinical characterization of the potent and selective BET inhibitor INCB057643 in models of hematologic malignancies. Cancer Research. Volume 77, Issue 13 Supplement, pp. 5071.

  [2] Ramiro V, Gianluca C, et al. BET inhibitors INCB054329 and INCB057643 display significant activity in androgen-independent prostate cancer models. Volume 77, Issue 13 Supplement, pp. 5080.