| Structural highlights
4fhj 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: | PIK3CG (Homo sapiens) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Publication Abstract from PubMed
mTOR is a critical regulator of cellular signaling downstream of multiple growth factors. The mTOR/PI3K/AKT pathway is frequently mutated in human cancers and is thus an important oncology target. Herein we report the evolution of our program to discover ATP-competitive mTOR inhibitors that demonstrate improved pharmacokinetic properties and selectivity compared to our previous leads. Through targeted SAR and structure-guided design, new imidazopyridine and imidazopyridazine scaffolds were identified that demonstrated superior inhibition of mTOR in cellular assays, selectivity over the closely related PIKK family and improved in vivo clearance over our previously reported benzimidazole series.
Discovery and optimization of potent and selective imidazopyridine and imidazopyridazine mTOR inhibitors.,Peterson EA, Boezio AA, Andrews PS, Boezio CM, Bush TL, Cheng AC, Choquette D, Coats JR, Colletti AE, Copeland KW, Dupont M, Graceffa R, Grubinska B, Kim JL, Lewis RT, Liu J, Mullady EL, Potashman MH, Romero K, Shaffer PL, Stanton MK, Stellwagen JC, Teffera Y, Yi S, Cai T, La DS Bioorg Med Chem Lett. 2012 Jun 16. PMID:22765895[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Peterson EA, Boezio AA, Andrews PS, Boezio CM, Bush TL, Cheng AC, Choquette D, Coats JR, Colletti AE, Copeland KW, Dupont M, Graceffa R, Grubinska B, Kim JL, Lewis RT, Liu J, Mullady EL, Potashman MH, Romero K, Shaffer PL, Stanton MK, Stellwagen JC, Teffera Y, Yi S, Cai T, La DS. Discovery and optimization of potent and selective imidazopyridine and imidazopyridazine mTOR inhibitors. Bioorg Med Chem Lett. 2012 Jun 16. PMID:22765895 doi:10.1016/j.bmcl.2012.06.033
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