3KBA

Progesterone receptor bound to sulfonamide pyrrolidine partial agonist

3KBA の概要

• エントリーDOI: 10.2210/pdb3kba/pdb
• 分子名称: Progesterone receptor, 2-chloro-4-{(2-methylbenzyl)[(3S)-1-(methylsulfonyl)pyrrolidin-3-yl]amino}benzonitrile, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: nuclear receptor, transcription, transcription regulation
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus. Isoform A: Nucleus. Isoform 4: Mitochondrion outer membrane : P06401
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59412.65

構造登録者

Kallander, L.S.,Washburn, D.G.,Williams, S.P.,Madauss, K.P. (登録日: 2009-10-20, 公開日: 2009-12-08, 最終更新日: 2024-02-21)

主引用文献

Kallander, L.S.,Washburn, D.G.,Hoang, T.H.,Frazee, J.S.,Stoy, P.,Johnson, L.,Lu, Q.,Hammond, M.,Barton, L.S.,Patterson, J.R.,Azzarano, L.M.,Nagilla, R.,Madauss, K.P.,Williams, S.P.,Stewart, E.L.,Duraiswami, C.,Grygielko, E.T.,Xu, X.,Laping, N.J.,Bray, J.D.,Thompson, S.K.
Improving the developability profile of pyrrolidine progesterone receptor partial agonists.
Bioorg.Med.Chem.Lett., 20:371-374, 2010

PubMed Abstract: The previously reported pyrrolidine class of progesterone receptor partial agonists demonstrated excellent potency but suffered from serious liabilities including hERG blockade and high volume of distribution in the rat. The basic pyrrolidine amine was intentionally converted to a sulfonamide, carbamate, or amide to address these liabilities. The evaluation of the degree of partial agonism for these non-basic pyrrolidine derivatives and demonstration of their efficacy in an in vivo model of endometriosis is disclosed herein.

PubMed: 19926282
DOI: 10.1016/j.bmcl.2009.10.092

実験手法

X-RAY DIFFRACTION (2 Å)