product name VER155008
Description: VER-155008 is a potent Hsp70 family inhibitor with IC50 of 0.5 μM, 2.6 μM, and 2.6 μM in cell-free assays for HSP70, HSC70, and GRP78, respectively, it has >100-fold selectivity over HSP90. VER 155008 has been shown to contribute to cancer cell survival via anti-apoptotic functions, that inhibits Hsp70 with IC50 of 0.5 μM as well as heat shock cognate 71 kDa protein (Hsc70) and 78 kDa glucose-regulated protein (Grp78) but to a lesser extent.
References: J Med Chem. 2011 Jul 28;54(14):5082-96.
467.25
Formula
C25H23Cl2N7O4
CAS No.
1030612-90-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 93 mg/mL (199.0 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
1% CMC+0.5% Tween-80: 30 mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: MK-8245, a phenoxy piperidine isoxazole derivative, has been identified as a potent and liver-specific SCD inhibitor. It contains a tetrazole acetic acid moiety, which is the key molecule for OATPs recognition and liver-targeting. MK-8245 displays similar potencies against human, rat and mouse SCD1 with IC50 values of 1 nM for human SCD1 and 3 nM for both rat SCD1 and mouse SCD1. MK-8245 exhibits a significant SCD inhibition in the rat hepatocyte assay which contains functional, active OATPs with IC50 of 68 nM, while being only weakly active in the HepG2 cell assay which is devoid of active OATPs with IC50 of ~1 μM. MK-8245 displays highly selective activity for the Δ-5 and Δ-6 desaturases (i.e., >100000 μM vs rat and human Δ5D and Δ6D as assessed in the HepG assay. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | Administration of MK-8245 at 10 mg/kg in mice exhibits a tissue distribution profile concentrated in the liver. It shows a liver-to-Harderian gland ratio of 21, suggesting a high degree of liver-targeting compared to a systemically distributed compound with liver-to-Harderian gland ratio of 1.5. Oral dosing of MK-8245 in mice, rats, dogs, and rhesus monkeys demonstrates that MK-8245 is distributed mainly to the liver, with low exposure in tissues associated with potential adverse events. The liver-to-skin ratios are >30:1 in all four species. Administration of MK-8245 to eDIO mice before the glucose challenge improves glucose clearance in a dose-dependent manner with ED50 of 7 mg/kg. |
| Animal model | Male C57/Bl6 mice |
| Formulation & Dosage | Suspended in 1% methocel in saline; 30 mg/kg; oral gavage |
| References | J Med Chem. 2011 Jul 28;54(14):5082-96. |
