product name MK-8617
Description: MK-8617 is a potent, selective, orally available pan-inhibitor of Hypoxia-inducible factor prolyl hydroxylase 1−3 (HIF PHD1−3), inhibiting PHD1, 2, 3 with IC50 values of 1.0, 1.0 and 14 nM, respectively. MK-8617 is used for the treatment of anemia (10-19 hr dog and moneky t1/2). MK-8617 is not a significant inhibitor of the cytochrome p450 enzymes in vitro (IC50), CYP1A2, 3A4, 2B6, 2C9, 2C19, or 2D6, >60 μM, and is a moderate reversible inhibitor of CYP2C8 at 1.6 μM in vitro.
References: J Med Chem. 2016 Dec 22;59(24):11039-11049.
443.45
Formula
C24H21N5O4
CAS No.
1187990-87-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 88 mg/mL (198.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19426738
| In Vitro |
In vitro activity: MK-8617 is not a significant inhibitor of the cytochrome p450 enzymes in vitro (IC50), CYP1A2, 3A4, 2B6, 2C9, 2C19, or 2D6, >60 μM, and is a moderate reversible inhibitor of CYP2C8 at 1.6 μM in vitro. MK-8617 is inactive when screened at 10 μM against a general panel of 171 radioligand binding and enzymatic assays. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | Tritiated MK-8617 exhibits minimal metabolic turnover in liver microsomes (+NADPH) from rat, dog, and monkey (<10% turover) but significant turnover in human liver microsomes (34% turnover) after 60 min (10 μM compound, 1 mg/mL microsomal protein). In terms of its pharmacokinetic profile, MK-8617 shows good oral bioavailability across species (36−71%), with low clearance and volume of distribution. The compound still has a relatively long elimination half-life across preclinical species. In mice (C57Bl/6), single doses of 5 and 15 mpk po (n = 3) causes increases in circulating reticulocytes measured on both 3 and 4 days postcompound challenge. In rat (Sprague−Dawley), a single dose titration of 1.5, 5, and 15 mpk po (n = 5) causes a large increase in serum erythropoietin(EPO) levels of 1.7-, 8-, and 204-fold relative to vehicle, respectively. Increases in circulating reticulocytes are observed at 5 and 15 mg/kg 3 days after challenge and, with the 15 mg dose, at 4 days after challenge. |
| Animal model | C57Bl/6 mice |
| Formulation & Dosage | Dissolved in DMSO/PEG400/water (5:40:55, v/v/v); 1 mg/kg po, 0.5 mg/kg iv; i.v. or p.o. |
| References | J Med Chem. 2016 Dec 22;59(24):11039-11049. |
