| Chemical Properties | Back Directory | [density ]
1.33±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
DMSO: 2mg/mL, clear | [form ]
Solid | [pka]
12.17±0.40(Predicted) | [color ]
White to off-white | [InChIKey]
JUVJFMVGYBBDKN-HDJSIYSDSA-N | [SMILES]
O=C(C1=C2C(NC=C2)=NC(C3=CN=CS3)=C1)N[C@H]4CC[C@@H](CC4)OCCOC |
| Hazard Information | Back Directory | [Description]
MK-0159 is a CD38 enzymatic inhibitor. Mice treated with MK-0159 show strong protection from myocardial damage upon cardiac I/R injury compared to those treated with NAD+ precursors (nicotinamide riboside) or another CD38 inhibitor. | [Uses]
MK-0159 is an orally active, potent and selective CD38 inhibitor, with IC50 values of 22, 3, and 70 nM for human, mouse and rat CD38, respectively. MK-0159 also shows good microsomal stability for human and rodent liver microsomes. MK-0159 increases NAD+ (nicotinamide adenine dinucleotide) and reduces ADPR (adenosine diphosphate ribose) in whole blood and heart[1]. | [in vivo]
MK-0159 (3-30 mg/kg, p.o., a single dose) increases systemic NAD+ and decreases ADPR levels (the product and substrate of CD38 enzymatic activity) in blood and heart of mice[1].
MK-0159 (30 mg/kg, p.o.) reduces infarct size in cardiac I/R injury mice[2].
MK-0159 (30 mg/kg, oral gavage, twice a day for 9 days) reverses mitochondrial defect, restores CD8+ T cell function and inhibits virally induced organ inflammation in BXD2 lupus-prone mice with LCMV infection[2].
| Animal Model: | Cardiac I/R injury mice[1] | | Dosage: | 30 mg/kg | | Administration: | p.o. | | Result: | Reduced infarct size, and the combination of MK-0159 and NAD+ precursor significantly reduced the infarct size compared to MK-0159 alone.
Increased whole heart NAD+ levels and decreased ADPR in the heart.
|
| [References]
[1] Lagu B, et al. Orally Bioavailable Enzymatic Inhibitor of CD38, MK-0159, Protects against Ischemia/Reperfusion Injury in the Murine Heart. J Med Chem. 2022 Jun 28. DOI:10.1021/acs.jmedchem.2c00688
[2] Chen PM, et al. CD38 reduces mitochondrial fitness and cytotoxic T cell response against viral infection in lupus patients by suppressing mitophagy. Sci Adv. 2022 Jun 17;8(24):eabo4271. DOI:10.1126/sciadv.abo4271 |
|
| Company Name: |
Merck KGaA
|
| Tel: |
21-20338288 |
| Website: |
www.sigmaaldrich.cn |
|