P7C3

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Background

Target: Nicotinamide phosphoribosyltransferase (NAMPT)IC50: N/AP7C3 is an orally bioavailable proneurogenic and neuroprotective chemical which targets NAMPT enzyme [1]. NAMPT, the rate-limiting enzyme in the salvage pathway plays a critical role in the conversion of nicotinamide into nicotinamide adenine mononucleotide (NMN) and nicotinamide adenine dinucleotide (NAD) [2].In vitro: P7C3 (1, 10, and 100 nM) preserved mitochondrial membrane potential in parallel to proneurogenic activity [1]. Administration of P7C3 (5 μM) to U2OS cells treated with doxorubicin, which induced NAD depletion, induced an increasing in intracellular NAD levels and concomitant protection from doxorubicin-mediated toxicity through the NAMPT-mediated salvage [2].In vivo: P7C3 (5 to 40 mg/kg, oral administration) showed its proneurogenic activity through protecting newborn neurons from apoptosis. In addition, P7C3 (10 mg/kg, oral administration) enhanced hippocampal neurogenesis, preserved cognitive capacity, and prevented weight loss in terminally aged rats [1]. P7C3 (437.5 μg, twice daily via i.p. injections) treatment restored hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome [3].

1. Pieper AA, Xie S, Capota E, Estill SJ, Zhong J, Long JM, et al. Discovery of a proneurogenic, neuroprotective chemical. Cell. 2010;142(1):39-51.
2. Wang G, Han T, Nijhawan D, Theodoropoulos P, Naidoo J, Yadavalli S, et al. P7C3 neuroprotective chemicals function by activating the rate-limiting enzyme in NAD salvage. Cell. 2014;158(6):1324-34.
3. Latchney SE, Jaramillo TC, Rivera PD, Eisch AJ, Powell CM. Chronic P7C3 treatment restores hippocampal neurogenesis in the Ts65Dn mouse model of Down Syndrome [Corrected]. Neurosci Lett. 2015;591:86-92.