1262633-07-7Relevant academic research and scientific papers
PHARMACEUTICAL COMPOSITION WITH ENHANCED EFFICACY FOR INHIBITING ANGIOGENESIS
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Paragraph 0062, (2014/10/29)
The present invention relates to a pharmaceutical composition for inhibiting angiogenesis and a novel sulfonyl amide derivative compound which can be useful for the prevention or treatment of angiogenesis-related diseases or disorders. Since the compound
Development of a novel class of mitochondrial ubiquinol-cytochrome c reductase binding protein (UQCRB) modulators as promising antiangiogenic leads
Jung, Hye Jin,Cho, Misun,Kim, Yonghyo,Han, Gyoonhee,Kwon, Ho Jeong
, p. 7990 - 7998 (2014/12/10)
Recently, we identified a novel therapeutic target and a small molecule for regulating angiogenesis. Our study showed that ubiquinol-cytochrome c reductase binding protein (UQCRB) of the mitochondrial complex III plays a crucial role in hypoxia-induced angiogenesis via mitochondrial reactive oxygen species (ROS) mediated signaling. Herein, we developed new synthetic small molecules that specifically bind to UQCRB and regulate its function. To improve the pharmacological properties of 6-((1-hydroxynaphthalen-4-ylamino)dioxysulfone)-2H-naphtho[1,8-bc]thiophen-2-one (HDNT), a small molecule that targets UQCRB, a series of HDNT derivatives were designed and synthesized. Several derivatives showed a significant increase in hypoxia inducible factor 1 (HIF-1) inhibitory potency compared to HDNT. The compounds bound to UQCRB and suppressed mitochondrial ROS-mediated hypoxic signaling, resulting in potent inhibition of angiogenesis without inducing cytotoxicity. Notably, one of these new derivatives significantly suppressed tumor growth in a mouse xenograft model. Therefore, these mitochondrial UQCRB modulators could be potential leads for the development of novel antiangiogenic agents.
Identifying chelators for metalloprotein inhibitors using a fragment-based approach
Jacobsen, Jennifer A.,Fullagar, Jessica L.,Miller, Melissa T.,Cohen, Seth M.
experimental part, p. 591 - 602 (2011/03/21)
Fragment-based lead design (FBLD) has been used to identify new metal-binding groups for metalloenzyme inhibitors. When screened at 1 mM, a chelator fragment library (CFL-1.1) of 96 compounds produced hit rates ranging from 29% to 43% for five matrix meta
