生物活性

• 描述CBL-0137 is a metabolically stable curaxin that activates p53 with an EC50 value of 0.37 µM and inhibits NF-κB with an EC50 of 0.47 µM. It functionally inactivates the facilitates chromatin transcription complex (FACT), driving the effects on p53 and NF-κB and promoting cancer cell death.

• 动物研究
  剂量	Mice: 25 mg/kg[3] (p.o.); 90 mg/kg[3] (i.p.); 50 mg/kg[4] (i.v.)
  给药途径	p.o., i.p., i.v.

• 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
  NCT02931110	Hematological Malignancies	Phase 1	Recruiting	August 2019	United States, Georgia ... more >> Claude Sportes Recruiting Augusta, Georgia, United States, 30912 Contact: Claude Sportes, MD    706-721-2505    csportes@augusta.edu    United States, New York Roswell Park Cancer Institute Recruiting Buffalo, New York, United States, 14263 Contact: Francisco J Hernandez, MD       Fhernandez@roswellpark.org    Principal Investigator: Francisco J Hernandez, MD          United States, Ohio University Hospitals Case Medical Recruiting Cleveland, Ohio, United States, 44106 Contact: Paolo F Caimi, MD          Principal Investigator: Paolo F Caimi, MD Collapse <<
  NCT01905228	Solid Tumors ... more >>Glioblastoma Collapse <<	Phase 1	Recruiting	November 2019	United States, New York ... more >> Roswell Park Cancer Institute Recruiting Buffalo, New York, United States, 14263 Contact: Renuka V. Iyer, MD       renuka.iyer@roswellpark.org    Principal Investigator: Renuka V. Iyer, MD          United States, Ohio University Hospital of Cleveland Recruiting Cleveland, Ohio, United States, 44106 Contact: Afshin Dowlati, MD    216-844-5181    afshin.dowlati@case.edu    Principal Investigator: Afshin Dowlati, MD          Cleveland Clinic Recruiting Cleveland, Ohio, United States, 44195 Contact: Manmeet Ahluwalia, MD       ahluwam@CCF.org    Principal Investigator: Manmeet Ahluwalia, MD          United States, Texas CTRC at The University of Texas Healh Science Center at San Antonio Recruiting San Antonio, Texas, United States, 78229 Contact: John Sarantopoulos, MD       saratopoulo@uthscsa.edu    Principal Investigator: John Sarantopoulos, MD Collapse <<
  NCT03727789	Advanced Cutaneous Melanoma of... more >> the Extremity Advanced Sarcoma of the Extremity Clinical Stage III Cutaneous Melanoma AJCC v8 Clinical Stage IV Cutaneous Melanoma AJCC v8 Pathologic Stage IIIB Cutaneous Melanoma AJCC v8 Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 Pathologic Stage IV Cutaneous Melanoma AJCC v8 Recurrent Cutaneous Melanoma of the Extremity Recurrent Sarcoma of the Extremity Stage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8 Stage IIIA Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8 Stage IIIB Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8 Stage IV Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8 Collapse <<	Phase 1	Not yet recruiting	August 8, 2022	United States, New York ... more >> Roswell Park Cancer Institute Not yet recruiting Buffalo, New York, United States, 14263 Contact: Joseph J. Skitzki    716-845-1212    Joseph.Skitzki@roswellpark.org    Principal Investigator: Joseph J. Skitzki Collapse <<

• 参考文献

• [1] Carter DR, Murray J, et al. Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma. Sci Transl Med. 2015 Nov 4;7(312):312ra176.

  [2] Burkhart C, Fleyshman D, et al. Curaxin CBL0137 eradicates drug resistant cancer stem cells and potentiates efficacy of gemcitabine in preclinical models of pancreatic cancer. Oncotarget. 2014 Nov 30;5(22):11038-53.

  [3] Barone TA, Burkhart CA, et al. Anticancer drug candidate CBL0137, which inhibits histone chaperone FACT, is efficacious in preclinical orthotopic models of temozolomide-responsive and -resistant glioblastoma. Neuro Oncol. 2017 Feb 1;19(2):186-196.

  [4] Lock R, Carol H, et al. Initial testing (stage 1) of the curaxin CBL0137 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2017 Apr;64(4).