301313-43-9Relevant articles and documents
Targeting STAT3 anti-apoptosis pathways with organic and hybrid organic-inorganic inhibitors
Ball, Zachary T.,Cooper, Julian C.,Kasembeli, Moses M.,Kolosov, Mikhail I.,Krueger, Michael J.,Liu, Wei,Mangubat-Medina, Alicia E.,Minus, Matthew B.,Munoz, Jaime O.,Redell, Michele S.,Stevens, Alexandra M.,Tweardy, David J.,Wang, Haopei
, p. 3288 - 3296 (2020/05/14)
Recurrence and drug resistance are major challenges in the treatment of acute myeloid leukemia (AML) that spur efforts to identify new clinical targets and active agents. STAT3 has emerged as a potential target in resistant AML, but inhibiting STAT3 function has proven challenging. This paper describes synthetic studies and biological assays for a naphthalene sulfonamide inhibitor class of molecules that inhibit G-CSF-induced STAT3 phosphorylation in cellulo and induce apoptosis in AML cells. We describe two different approaches to inhibitor design: first, variation of substituents on the naphthalene sulfonamide core allows improvements in anti-STAT activity and creates a more thorough understanding of anti-STAT SAR. Second, a novel approach involving hybrid sulfonamide-rhodium(ii) conjugates tests our ability to use cooperative organic-inorganic binding for drug development, and to use SAR studies to inform metal conjugate design. Both approaches have produced compounds with improved binding potency.In vivoand in cellulo experiments further demonstrate that these approaches can also lead to improved activity in living cells, and that compound3aaslows disease progression in a xenograft model of AML.
Discovery of N-(3-((7H-purin-6-yl)thio)-4-hydroxynaphthalen-1-yl)- sulfonamide derivatives as novel protein kinase and angiogenesis inhibitors for the treatment of cancer: Synthesis and biological evaluation. Part III
Xu, Fuming,Xu, Hao,Wang, Xuejian,Zhang, Lei,Wen, Qingli,Zhang, Yingjie,Xu, Wenfang
, p. 1487 - 1495 (2014/03/21)
A novel series of N-(3-((7H-purin-6-yl)thio)-4-hydroxynaphthalen-1-yl)- sulfonamides were designed and synthesized. Biological characterization revealed that several compounds exerted enhanced anti-proliferative activity against human umbilical vein endothelial cells (HUVECs) and several cancer cell lines and high specific protein kinase and angiogenesis inhibitory activities. Compared with our previously synthesized compounds, the substitution of sulfonamide structure for amide fragment played an essential role for the advance of inhibitory activities. In addition, the replacement of 1H-1,2,4-triazole ring by 7H-purine did not result in obvious decrease of inhibition efficacy, indicating that the sulfonamide structure contributes even more to the inhibition efficacy than the 1H-1,2,4-triazole ring. Among these compounds, compound 9n demonstrated comparable in vitro antiangiogenic activities to pazopanib in both HUVEC tube formation assay and the rat thoracic aorta rings (TARs) test. Meanwhile, compound 9n was identified to inhibit Akt1 (IC50 = 1.73 μM) and Abl tyrosine kinase (IC50 = 1.53 μM) effectively.
