生物活性

• 描述Indisulam is an aryl sulfonamide drug with selective anticancer activity. Indisulam promotes the recruitment of RBM39 (RNA binding motif protein 39) to the CUL4-DCAF15 E3 ubiquitin ligase, leading to RBM39 polyubiquitination and proteasomal degradation^[3]. Similarly to the clinically used drugs acetazolamide, methazolamide and topiramate, E7070 showed inhibition constants in the range of 15-31nM against isozymes I, II and IX, being slightly less effective as a CA IV inhibitor (K(i) of 65nM) ^[4]. Indisulam 500 mg m(-2) in combination with carboplatin 6 mg min ml(-1) was identified not to cause dose limiting toxicity, but a delay of re-treatment by 1 week was required regularly to allow recovery from myelosuppression^[5].
• 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
  NCT03485950	Other Infectious Diseases	Phase 2	Recruiting	May 2019	United States, Texas ... more >> University of Texas MD Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Contact       iraad@mdanderson.org Collapse <<
  NCT00165867	Colorectal Cancer	Phase 2	Completed	-	France ... more >> Hôpitaux Civils de Colmar Colmar, France, F- 68024 CRLC Val d'Aurelle Montpellier, France, F-34298 Centre Antoine Lacassagne Nice, France, F-06189 United Kingdom Aberdeen Royal Infirmary Aberdeen, United Kingdom, AB25 2ZN Beatson Oncology Centre Glasgow, United Kingdom, G11 6NT Cookridge Hospital Leeds, United Kingdom, LS16 6QB Leicester Royal Infirmary Leicester, United Kingdom, LE1 5WW Collapse <<
  NCT00059735	Kidney Neoplasms ... more >> Carcinoma, Renal Cell Adenocarcinoma, Renal Cell Collapse <<	Phase 2	Completed	-	United States, California ... more >> Sacramento, California, United States, 95817 United States, New York Bronx, New York, United States, 10466 New York, New York, United States, 10021 New York, New York, United States, 10032 France Villejuif Cedex, France, 94805 Collapse <<

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• 参考文献

• [1] Talbot DC, von Pawel J, et al. A randomized phase II pharmacokinetic and pharmacodynamic study of indisulam as second-line therapy in patients with advanced non-small cell lung cancer. Clin Cancer Res. 2007 Mar 15;13(6):1816-22.

  [2] Abbate F, Casini A, et al. Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isozymes I and II, and transmembrane, tumor-associated isozyme IX. Bioorg Med Chem Lett. 2004 Jan 5;14(1):217-23.

  [3] Han T, Goralski M, Gaskill N, Capota E, Kim J, Ting TC, Xie Y, Williams NS, Nijhawan D. Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science. 2017 Apr 28;356(6336):eaal3755

  [4] Abbate F, Casini A, Owa T, Scozzafava A, Supuran CT. Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isozymes I and II, and transmembrane, tumor-associated isozyme IX. Bioorg Med Chem Lett. 2004 Jan 5;14(1):217-23

  [5] Dittrich C, Zandvliet AS, Gneist M, Huitema AD, King AA, Wanders J. A phase I and pharmacokinetic study of indisulam in combination with carboplatin. Br J Cancer. 2007 Feb 26;96(4):559-66

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