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SKI-IIÊÇÇʰ±´¼¼¤Ã¸I£¨SPHK 1£©ºÍ2£¨SPHK 2£©µÄ³£ÓÃÒÖÖÆ¼Á¡£×î½üÒÑÏÔʾÆäÒÖÖÆ¶þÇâÉñ¾­õ£°·È¥±¥ºÍø£¨Des 1£©£¬AurelioµÈÈËÈÏΪʵ¼ÊÉÏÊÇÆä¿¹ÔöÖ³»îÐÔ¶ø²»ÊÇSPHKÒÖÖÆµÄÔ­Òò¡£»¯ºÏÎï34ÊÇSKI-IIµÄÀàËÆÎ²¢ÇÒÊÇÑ¡ÔñÐÔDes 1ÒÖÖÆ¼Á£¬Æä¶ÔSPHK 1»òSPHK 2¾ù²»ÏÔʾ»îÐÔ¡£34ÒÖÖÆPC 3ϸ°ûÉú³¤£¨GIC 50 = 0.34 ¦Ì M£©£¬µ«ÆäÖÐһЩ¿ÉÄÜÊÇÓÉÓÚÒÖÖÆÁíÒ»¸ö°Ðµã¡£Aurelio C. V. ScullinoµÈÈË´ÓÇʰ±´¼¼¤Ã¸µ½¶þÇâÉñ¾­õ£°·È¥±¥ºÍø£ºÒ»Öֽṹ£¿4-£¨£¨4-£¨4-Chlorophenyl£©thiazol-2-yl£©amino£©phenol£¨SKI-II£©µÄøÒÖÖÆºÍ¿¹°©»îÐԵĻîÐÔ¹ØÏµ£¨SAR£©Ñо¿-J. Med. Chem. 59 965-984 DOI£º10.1021/acs.jmedchem.5b01439.?
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SKI-II is a commonly used inhibitor of both sphingosine kinase I (SPHK1) and 2 (SPHK2). Recently it has been shown to inhibit dihydroceramide desaturase (Des1) which Aurelio et al. suggest is actually responsible for its anti-proliferative activity not SPHK inhibition. Compound 34 is an analog of SKI-II and is a selective Des1 inhibitor which shows no activity against either SPHK1 or SPHK2. 34 inhibits PC3 cell growth (GIC50 = 0.34 ??M) but some of this may be due to inhibition of another targetReferences Powered by Bioz See more details on BiozL. Aurelio C.V. Scullino et al.. ?€?From Sphingosine Kinase to Dihydroceramide desaturase: A Structure?Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II)?€? J. Med. Chem. 59 965-984 DOI: 10.1021/acs.jmedchem.5b01439.
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