3KBA

Progesterone receptor bound to sulfonamide pyrrolidine partial agonist

Summary for 3KBA

• Entry DOI: 10.2210/pdb3kba/pdb
• Descriptor: Progesterone receptor, 2-chloro-4-{(2-methylbenzyl)[(3S)-1-(methylsulfonyl)pyrrolidin-3-yl]amino}benzonitrile, SULFATE ION, ... (4 entities in total)
• Functional Keywords: nuclear receptor, transcription, transcription regulation
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus. Isoform A: Nucleus. Isoform 4: Mitochondrion outer membrane : P06401
• Total number of polymer chains: 2
• Total formula weight: 59412.65

Authors

Kallander, L.S.,Washburn, D.G.,Williams, S.P.,Madauss, K.P. (deposition date: 2009-10-20, release date: 2009-12-08, Last modification date: 2024-02-21)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2 Å)