3hdm
Crystal structure of serum and glucocorticoid-regulated kinase 1 in complex with compound 1Crystal structure of serum and glucocorticoid-regulated kinase 1 in complex with compound 1
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe lead serum and glucocorticoid-related kinase 1 (SGK1) inhibitors 4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid (1) and {4-[5-(2-naphthalenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl}acetic acid (2) suffer from low DNAUC values in rat, due in part to formation and excretion of glucuronic acid conjugates. These PK/glucuronidation issues were addressed either by incorporating a substituent on the 3-phenyl ring ortho to the key carboxylate functionality of 1 or by substituting on the group in between the carboxylate and phenyl ring of 2. Three of these analogs have been identified as having good SGK1 inhibition potency and have DNAUC values suitable for in vivo testing. Design and synthesis of orally bioavailable serum and glucocorticoid-regulated kinase 1 (SGK1) inhibitors.,Hammond M, Washburn DG, Hoang HT, Manns S, Frazee JS, Nakamura H, Patterson JR, Trizna W, Wu C, Azzarano LM, Nagilla R, Nord M, Trejo R, Head MS, Zhao B, Smallwood AM, Hightower K, Laping NJ, Schnackenberg CG, Thompson SK Bioorg Med Chem Lett. 2009 Aug 1;19(15):4441-5. Epub 2009 May 18. PMID:19497745[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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