NAMPT
NAMPT is the rate-limiting enzyme in this pathway and converts NAM to nicotinamide mononucleotide (NMN) by catalyzing the reversible addition of a ribose group from 5-phospho-α-D-ribosyl 1-pyrophosphate (PRPP) to NAM. To facilitate this reaction, NAMPT is autophosphorylated on H247, which enhances the affinity for NAM by 160,000-fold and increases enzymatic activity by 1,125-fold. Given that NAMPT is the rate-limiting enzyme in a key NAD recycling pathway, small changes in NAMPT activity can dramatically impact NAD metabolism and NAD dependent cellular processes. NAMPT was originally identified as a secreted cytokine-like factor that synergized with interleukin-7 and stem cell factor to promote pre-B-cell colony formation and, therefore, was initially designated PBEF (pre-B-cell enhancing factor).
NAMPT is ubiquitously expressed in all tissues and the coding sequence is highly conserved across mammalian species and lower organisms such as insects, sponges and prokaryotes. In most cell types, NAMPT is expressed intracellularly in the cytoplasm, nucleus, and mitochondria and is commonly referred to as iNAMPT (intracellular NAMPT). A second, secreted form of NAMPT has also been observed and is referred to as eNAMPT (extracellular NAMPT) or visfatin. Enzymatic activity of eNAMPT has been demonstrated in NAMPT haplodeficient mice in which expression of eNAMPT is decreased resulting in lower plasma NMN levels and defective insulin secretion in pancreatic β –cells upon glucose stimulation. eNAMPT promoted macrophage survival following endoplasmic stressors or apoptotic inducers that are observed in obesity-associated diseases by stimulating interleukin-6 secretion and subsequent STAT3 activation.
References
1.Sampath D, et al. Pharmacol Ther. 2015;151:16–31.
NAMPT is ubiquitously expressed in all tissues and the coding sequence is highly conserved across mammalian species and lower organisms such as insects, sponges and prokaryotes. In most cell types, NAMPT is expressed intracellularly in the cytoplasm, nucleus, and mitochondria and is commonly referred to as iNAMPT (intracellular NAMPT). A second, secreted form of NAMPT has also been observed and is referred to as eNAMPT (extracellular NAMPT) or visfatin. Enzymatic activity of eNAMPT has been demonstrated in NAMPT haplodeficient mice in which expression of eNAMPT is decreased resulting in lower plasma NMN levels and defective insulin secretion in pancreatic β –cells upon glucose stimulation. eNAMPT promoted macrophage survival following endoplasmic stressors or apoptotic inducers that are observed in obesity-associated diseases by stimulating interleukin-6 secretion and subsequent STAT3 activation.
References
1.Sampath D, et al. Pharmacol Ther. 2015;151:16–31.
Metabolic Enzyme/Protease
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NAMPT
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Nampt activator-2
产品货号 : M36469
cas no: 2237268-90-3
Nampt activator-2 (compound 34) 是一种有效的 NAMPT 激活剂,EC50 为 0.023 μM。 Nampt activator-2 对 CYP2C9 (0.060 μM)、2D6 (0.41 μM) 和 2C19 (0.59 μM) 表现出中等活性。 -
Nampt activator-1
产品货号 : M36082
cas no: 701929-65-9
Nampt activator-1 (compound 1) 是一种有效的烟酰胺磷酸基转移酶 (NAMPT) 激活剂,其 EC50 为 3.3-3.7 μM。 -
CB30865
产品货号 : M33305
cas no: 206275-15-2
CB30865 (ZM 242421) 是一种烟酰胺磷酸核糖转移酶 (Nampt) 抑制剂,具有很强的细胞毒性。CB30865 在体外能抑制多种人类肿瘤细胞系 (IC50 值在 1-10 nM 范围内)。 -
OT-82
产品货号 : M33050
cas no: 1800487-55-1
OT-82 是一种强效、选择性和具有口服活性的 NAMPT 的抑制剂。OT-82 对造血源细胞有选择性毒性,以 NAD+依赖方式诱导细胞死亡。OT-82 是一种很有前途的抗肿瘤试剂 (antineoplastic agent),用于血液系统恶性肿瘤的研究。 -
LB-60-OF61
产品货号 : M32993
cas no: 794461-93-1
LB-60-OF61 是一种 NAMPT 抑制剂,是一种对 MYC 过表达细胞系具有选择性的细胞毒性化合物。