NAMPT Activator

SBI-797812 is an orally active nicotinamide phosphoribosyltransferase (NAMPT) activator. SBI-797812 shifts NAMPT to NMN formation, increases NAMPT affinity for ATP, stabilizes phosphorylated NAMPT, promotes consumption of the pyrophosphate by-product, and blunts feedback inhibition by NAD⁺. SBI-797812 increases intracellular nicotinamide mononucleotide (NMN) and elevates liver NAD⁺ in mice.

SR-32685 is a NAMPT activator and neuroprotective agent. SR-32685 enhances the enzymatic activity of hNAMPT, prevents intracellular NAD depletion, and protects neurons from death induced by toxic misfolded prion proteins. SR-32685 can be used in the research of protein misfolding neurodegenerative diseases and metabolic diseases.

NAT is an initial hit of NAMPT activator with an EC₅₀ of 5.7 μM and a K_D of 379 nM. NAMPT is the rate-limiting enzyme in the NAD salvage pathway, which makes it an attractive target for the research of many diseases associated with NAD exhaustion such as neurodegenerative diseases.

NAMPT activator-3, a NAT derivative, is a NAMPT activator with an EC₅₀ of 2.6 μM and a K_D of 132 nM. NAMPT activator-3 effectively protects cultured cells from FK866 (HY-50876)-mediated toxicity. NAMPT activator-3 exhibits strong neuroprotective efficacy in a chemotherapy-induced peripheral neuropathy (CIPN) mouse model without any overt toxicity.

Nampt activator-1 is a nicotinamide phosphoribosyltransferase (NAMPT) activator, with an EC₅₀ of 3.3~3.7 μM. Nampt activator-1 enhances the enzymatic activity of NAMPT. Nampt activator-1 can be used for research related to metabolic disorders.

Nampt activator-2 (compound 34) is a potent NAMPT activator, with EC₅₀ of 0.023 μM. Nampt activator-2 shows moderate activity against CYP2C9 (0.060 μM), 2D6 (0.41 μM) and 2C19 (0.59 μM).

Nampt activator-4 is an orally active NAMPT activator, with an EC₅₀ of 58 nM and a K_a of 85.38 nM against human NAMPT. Nampt activator-4 effectively relieves the feedback inhibition of nicotinamide and NAD⁺, thereby enhancing enzymatic activity and significantly increasing intracellular NAD⁺ levels. Nampt activator-4 exhibits moderate stability in human and mouse liver microsomes. Nampt activator-4 shows low to moderate inhibitory effects on cytochrome P450 (especially CYP3A4). Nampt activator-4 can be used for the research of type 2 diabetes and related metabolic disorders.

Myricanol is a diarylheptanoid and a Nampt activator. Myricanol exerts anti-inflammatory effects and alleviates glucocorticoid-induced muscle atrophy by increasing Sirtuin 1 (SIRT1) and PRDX5 activities while regulating inflammatory factors. Myricanol exhibits growth inhibition and induces apoptosis in human lung adenocarcinoma A549 cells. Myricanol promotes autophagy-mediated clearance of microtubule-associated protein tau to exert neuroprotective effects. Myricanol protects cardiovascular function by inhibiting PDGFRβ and NF-κB signaling pathways. Myricanol activates mitochondrial transcription factor A (TFAM) expression to exert anti-renal fibrosis effects. Myricanol improves insulin resistance through AMPK activation.

Carba1 is a bifunctional Carbazole (HY-D0204) derivative that activates nicotinamide phosphoribosyltransferase (NAMPT) and enhances NAD biosynthesis. Carba1 binds to colchicine site of tubulin, enhancing the anti-tumor effect of various chemotherapy drugs, such as Paclitaxel (HY-B0015). Carba1 exerts neuroprotective effect and can regulate cell energy metabolism. Carba1 can be used for the researches of cancer and chemotherapy-induced peripheral neuropathy (CIPN).

Nampt activator-5 is a NAMPT activator with a K_D value of 6.19 μM. Nampt activator-5 activates the rate-limiting enzyme in NAD⁺ biosynthesis and promotes NAD⁺ production. Nampt activator-5 delays the senescence process of senescent hepatocytes, extends the lifespan of *Caenorhabditis elegans*, and alleviates age-related dysfunction and abnormal biomarkers in naturally aged mice. Nampt activator-5 can be used in aging research.

JGB-1-155 is a positive allosteric modulators (N-PAMs), which enhances the activity of nicotinamide phosphoribosyltransferase NAMPT with EC₅₀ of 3.29 μM. JGB-1-155 counteracts the oxidative stress, through upregulating the NAD⁺ in THP-1 human monocytes. JGB-1-155 attenuates TNFα-induced ROS in HT-22 cells .

NAMPT activator-7 is a NAMPT activator with an EC₅₀ of <0.5 μM. NAMPT activator-7 can be used in research related to heart disease, Alzheimer's disease, Huntington's disease, Parkinson's disease and spinal cord injury.

NAMPT activator-9 (Compound DIPM) is an allosteric, non-competitive NAMPT activator, with an EC₅₀ of 3.366 μM against hNAMPT. NAMPT activator-9 enhances the enzymatic activity of NAMPT via an allosteric, non-competitive mechanism. NAMPT activator-9 increases intracellular NAD⁺ levels. NAMPT activator-9 restores myotube diameter and reduces the expression of atrophy markers Atrogin-1 and MuRF1. NAMPT activator-9 is applicable to research related to muscle atrophy.

SR-34831 is a NAMPT activator, NAD level stabilizer and neuroprotective agent. SR-34831 enhances the enzymatic activity of human NAMPT, prevents intracellular NAD depletion, and counteracts neuronal death induced by toxic misfolded prion proteins. SR-34831 exhibits metabolic stability in human liver microsomes and can be used for the research of protein misfolding neurodegenerative diseases.

NAMPT activator-6 is a nicotinamide phosphoribosyltransferase (NAMPT) activator. NAMPT activator-6 can be used for the synthesis of PROTACs, such as PROTAC NAMPT Degrader-1 (HY-163440). NAMPT activator-6 applies to the research of ovarian cancer.

NAMPT activator-7 is a NAMPT activator with an EC₅₀ of <0.5 μM. NAMPT activator-7 can be used in research related to heart disease, Alzheimer's disease, Huntington's disease, Parkinson's disease and spinal cord injury.

NAMPT activator-10 (Compound B11) is an orally active NAMPT activator with a target K_d value of 0.64 μM. NAMPT activator-10 activates the rate-limiting enzyme in NAD⁺ biosynthesis and promotes intracellular NAD⁺ synthesis. NAMPT activator-10 reduces lactate accumulation, enhances glycogen storage in the liver and muscle, increases tissue ATP production, improves exercise endurance and muscle strength, and exerts a protective effect against fatigue-induced muscle damage in mouse fatigue models. NAMPT activator-10 can be used in studies related to muscle fatigue.