| Structural highlights
3roc is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Gene: | CSBP, CSBP1, CSBP2, CSPB1, MAPK14, MXI2, THP-1 (Homo sapiens) |
| Activity: | Mitogen-activated protein kinase, with EC number 2.7.11.24 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Publication Abstract from PubMed
A novel series of highly potent and selective p38 MAP kinase inhibitors was developed originating from a substituted N-aryl-6-pyrimidinone scaffold. SAR studies coupled with in vivo evaluations in rat arthritis model culminated in the identification of 10 with excellent oral efficacy. Compound 10 exhibited a significantly enhanced dissolution rate compared to 1, translating to a high oral bioavailability (>90%) in rat. In animal studies 10 inhibited LPS-stimulated production of tumor necrosis factor-alpha in a dose-dependent manner and demonstrated robust efficacy comparable to dexamethasone in a rat streptococcal cell wall-induced arthritis model.
Substituted N-aryl-6-pyrimidinones: A new class of potent, selective, and orally active p38 MAP kinase inhibitors.,Devadas B, Selness SR, Xing L, Madsen HM, Marrufo LD, Shieh H, Messing DM, Yang JZ, Morgan HM, Anderson GD, Webb EG, Zhang J, Devraj RV, Monahan JB Bioorg Med Chem Lett. 2011 Jul 1;21(13):3856-60. Epub 2011 May 8. PMID:21620699[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Devadas B, Selness SR, Xing L, Madsen HM, Marrufo LD, Shieh H, Messing DM, Yang JZ, Morgan HM, Anderson GD, Webb EG, Zhang J, Devraj RV, Monahan JB. Substituted N-aryl-6-pyrimidinones: A new class of potent, selective, and orally active p38 MAP kinase inhibitors. Bioorg Med Chem Lett. 2011 Jul 1;21(13):3856-60. Epub 2011 May 8. PMID:21620699 doi:10.1016/j.bmcl.2011.05.006
|
