PDBsum entry 3kba

Transcription

PDB id: 3kba

Contents

Protein chain

244 a.a. *

Ligands

WOW ×2

SO4

Waters ×425

* Residue conservation analysis

PDB id:

3kba

Name:

Transcription

Title:

Progesterone receptor bound to sulfonamide pyrrolidine partial agonist

Structure:

Progesterone receptor. Chain: a, b. Fragment: steroid-binding region: unp residues 681-933. Synonym: pr, nuclear receptor subfamily 3 group c member 3. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pgr, nr3c3. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.00Å R-factor: 0.197 R-free: 0.250

Authors:

L.S.Kallander,D.G.Washburn,S.P.Williams,K.P.Madauss

Key ref:

L.S.Kallander et al. (2010). Improving the developability profile of pyrrolidine progesterone receptor partial agonists. Bioorg Med Chem Lett, 20, 371-374. PubMed id: 19926282

Date:

20-Oct-09 Release date: 08-Dec-09

Protein chains

P06401  (PRGR_HUMAN) -  Progesterone receptor from Homo sapiens

Seq: 933 a.a.

Struc: 244 a.a.

Enzyme reactions

• Enzyme class: E.C.?

Bioorg Med Chem Lett 20:371-374 (2010)

PubMed id: 19926282

Improving the developability profile of pyrrolidine progesterone receptor partial agonists.

L.S.Kallander, D.G.Washburn, T.H.Hoang, J.S.Frazee, P.Stoy, L.Johnson, Q.Lu, M.Hammond, L.S.Barton, J.R.Patterson, L.M.Azzarano, R.Nagilla, K.P.Madauss, S.P.Williams, E.L.Stewart, C.Duraiswami, E.T.Grygielko, X.Xu, N.J.Laping, J.D.Bray, S.K.Thompson.

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.