CD38-IN-6

CD38-IN-6 is an orally active CD38 inhibitor. CD38-IN-6 regulates NAD + metabolite levels in the liver of aged obese mice by increasing NAD + and NMN levels, and decreasing NAM and ADPR levels. CD38-IN-6 alleviates inflammatory responses in mice. CD38-IN-6 can be used for research related to obesity and inflammation ^[1].

In Vivo, CD38-IN-6 (1-10 mg/kg; p.o.; single dose / twice daily; for 49 days) regulates NAD+ metabolite levels in the liver of obese mice by increasing NAD+ and NMN levels, and decreasing NAM and ADPR levels^[1]. CD38-IN-6 (10 mg/kg; p.o.; twice daily; for 5 consecutive days) regulates NAD+ metabolite levels in the liver of aged obese mice by increasing NAD+ and NMN levels, and decreasing NAM and ADPR levels^[1]. CD38-IN-6 (10-30 mg/kg; p.o.) alleviates LPS -induced inflammatory responses in mice by reducing proinflammatory cytokines, regulating NAD+ metabolite levels in the spleen and liver, and decreasing CD38 expression and inflammatory gene expression in the liver^[1].

In Vitro, CD38-IN-6 (Compound 39) (8 different concentrations; 10 min) potently inhibits CD38-mediated NAD+ hydrolase activity in primary human M1 macrophages, with an IC₅₀ of 3.9 nM^[1]. CD38-IN-6 (50 nM; 24 h) significantly regulates intracellular calcium flux in CD38-expressing NH7-dCas9 Jurkat T cells^[1].

References:
[1]. Robert A. Volkmann, et al. Heteroaryl amide inhibitors of cd38. WO2022077034A1. 2023-04-09.