For research use only. Not for therapeutic Use.
GNE-495（Cat No.:I001742） is a potent and Selective MAP4K4 Inhibitor with IC50 of 3.7 nM.GNE-495 shows excellent potency and good PK and was used to demonstrate in vivo efficacy in a retinal angiogenesis model recapitulating effects that are observed in the inducible Map4k4 knockout mice.
| Catalog Number | I001742 |
| CAS Number | 1449277-10-4 |
| Synonyms | 8-amino-N-[1-(cyclopropylcarbonyl)-3-azetidinyl]-2-(3-fluorophenyl)-1,7-naphthyridine-5-carboxamide |
| Molecular Formula | C22H20FN5O2 |
| Purity | ≥95% |
| Target | MAP4K |
| Solubility | DMSO |
| Storage | -20°C |
| IUPAC Name | 8-amino-N-[1-(cyclopropanecarbonyl)azetidin-3-yl]-2-(3-fluorophenyl)-1,7-naphthyridine-5-carboxamide |
| InChI | InChI=1S/C22H20FN5O2/c23-14-3-1-2-13(8-14)18-7-6-16-17(9-25-20(24)19(16)27-18)21(29)26-15-10-28(11-15)22(30)12-4-5-12/h1-3,6-9,12,15H,4-5,10-11H2,(H2,24,25)(H,26,29) |
| InChIKey | FYXCIBJXJYBWPX-UHFFFAOYSA-N |
| SMILES | C1CC1C(=O)N2CC(C2)NC(=O)C3=CN=C(C4=C3C=CC(=N4)C5=CC(=CC=C5)F)N |
| Reference | 1:ACS Med Chem Lett. 2015 Jun 29;6(8):913-8. doi: 10.1021/acsmedchemlett.5b00174. eCollection 2015 Aug 13. Structure-Based Design of GNE-495, a Potent and Selective MAP4K4 Inhibitor with Efficacy in Retinal Angiogenesis.Ndubaku CO,Crawford TD,Chen H,Boggs JW,Drobnick J,Harris SF,Jesudason R,McNamara E,Nonomiya J,Sambrone A,Schmidt S,Smyczek T,Vitorino P,Wang L,Wu P,Yeung S,Chen J,Chen K,Ding CZ,Wang T,Xu Z,Gould SE,Murray LJ,Ye W, PMID: 26288693 PMCID: PMC4538449 DOI: 10.1021/acsmedchemlett.5b00174 </br><span>Abstract:</span> Diverse biological roles for mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) have necessitated the identification of potent inhibitors in order to study its function in various disease contexts. In particular, compounds that can be used to carry out such studies in vivo would be critical for elucidating the potential for therapeutic intervention. A structure-based design effort coupled with property-guided optimization directed at minimizing the ability of the inhibitors to cross into the CNS led to an advanced compound 13 (GNE-495) that showed excellent potency and good PK and was used to demonstrate in vivo efficacy in a retinal angiogenesis model recapitulating effects that were observed in the inducible Map4k4 knockout mice. |
