Structural highlights
Function
RORG_HUMAN Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock.
Publication Abstract from PubMed
Using structure-based drug design principles, we identified opportunities to reduce the lipophilicity of our tertiary sulfonamide RORc inverse agonists. The new analogs possessed improved RORc cellular potencies with >77-fold selectivity for RORc over other nuclear receptors in our cell assay suite. The reduction in lipophilicity also led to an increased plasma-protein unbound fraction and improvements in cellular permeability and aqueous solubility.
Reduction in lipophilicity improved the solubility, plasma-protein binding, and permeability of tertiary sulfonamide RORc inverse agonists.,Fauber BP, Rene O, de Leon Boenig G, Burton B, Deng Y, Eidenschenk C, Everett C, Gobbi A, Hymowitz SG, Johnson AR, La H, Liimatta M, Lockey P, Norman M, Ouyang W, Wang W, Wong H Bioorg Med Chem Lett. 2014 Aug 15;24(16):3891-7. doi: 10.1016/j.bmcl.2014.06.048., Epub 2014 Jun 25. PMID:25017032[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fauber BP, Rene O, de Leon Boenig G, Burton B, Deng Y, Eidenschenk C, Everett C, Gobbi A, Hymowitz SG, Johnson AR, La H, Liimatta M, Lockey P, Norman M, Ouyang W, Wang W, Wong H. Reduction in lipophilicity improved the solubility, plasma-protein binding, and permeability of tertiary sulfonamide RORc inverse agonists. Bioorg Med Chem Lett. 2014 Aug 15;24(16):3891-7. doi: 10.1016/j.bmcl.2014.06.048., Epub 2014 Jun 25. PMID:25017032 doi:http://dx.doi.org/10.1016/j.bmcl.2014.06.048
