GNE-617


Catalog No. size PriceQuantity
M6546-2 2mg solid $100
M6546-10 10mg solid $391

Description

Cas:1362154-70-8

Product Information:

GNE-617 is a potent nicotinamide phosphoribosyltransferase (NAMPT) inhibitor with IC50 value of 5nM. Prolonged inhibition of nicotinamide phosphoribosyltransferase (NAMPT) is a strategy for targeting cancer metabolism.

 

Chemical Formula: C21H15F2N3O3S

 

Exact Mass: 427.0802

 

Molecular Weight: 427.4258

 

Elemental Analysis: C, 59.01; H, 3.54; F, 8.89; N, 9.83; O, 11.23; S, 7.50

 

Synonym:

 

GNE-617

GNE 617

GNE617

 

Chemical Name:

N-(4-((3,5-difluorophenyl)sulfonyl)benzyl)imidazo[1,2-a]pyridine-6-carboxamide

 

InChi Key:

XRDVXQQZLHVEQZ-UHFFFAOYSA-N

 

InChi Code:

InChI=1S/C21H15F2N3O3S/c22-16-9-17(23)11-19(10-16)30(28,29)18-4-1-14(2-5-18)12-25-21(27)15-3-6-20-24-7-8-26(20)13-15/h1-11,13H,12H2,(H,25,27)

 

Smiles Code:

O=C(C1=CN2C(C=C1)=NC=C2)NCC3=CC=C(S(=O)(C4=CC(F)=CC(F)=C4)=O)C=C3

 

 

Technical Data:

 

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

 

In Vitro

The activity ofGNE-617 hydrochloride is evaluated on a panel 53 non-small cell lung cancer (NSCLC) cell lines in the presence or absence of 10 μM nicotinic acid. GNE-617 inhibits NAMPT IC50 of 18.9 nM in A549 cell.The majority of cell lines exhibit a steep dose response to GNE-617 when evaluated by decrease in ATP or total nucleic acid, and the cytotoxicity is completely rescued by simultaneous addition of nicotinic acid. The majority of the cell lines tested have IC50 values below 100 nM, with approximately half with IC50 values less than 10 nM. Eighteen cell lines are not rescued with nicotinic acid, and these non-rescuable cell lines tended to have lower IC50 values (P=0.008, Fisher exact test, IC50<10 nM vs. ≥10 nM).

 

In Vivo

In rats, GNE-617 hydrochloride (administered QD) and GNE-875 (administered BID) are associated with more severe retinal toxicity at similar exposures and dosing duration compared with GMX-1778 (administered BID). The mouse efficacy studies using GNE-617, GNE-618, and GMX-1778 are designed to assess efficacy and opportunistically used to assess retinal toxicity in mice. NAMPTi retinal toxicity is observed with GNE-617 and GMX-1778; however, the different study durations between GNE-617 and GMX-1778 do not allow for direct comparison of retinal toxicity.

 

 

References

 

  1. Preyat N, Leo O. Complex role of nicotinamide adenine dinucleotide in the regulation of programmed cell death pathways. Biochem Pharmacol. 2016 Feb 1;101:13-26. doi: 10.1016/j.bcp.2015.08.110. Epub 2015 Sep 3. PubMed PMID: 26343585.

 

  1. Zak M, Liederer BM, Sampath D, Yuen PW, Bair KW, Baumeister T, Buckmelter AJ, Clodfelter KH, Cheng E, Crocker L, Fu B, Han B, Li G, Ho YC, Lin J, Liu X, Ly J, O'Brien T, Reynolds DJ, Skelton N, Smith CC, Tay S, Wang W, Wang Z, Xiao Y, Zhang L, Zhao G, Zheng X, Dragovich PS. Identification of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with no evidence of CYP3A4 time-dependent inhibition and improved aqueous solubility. Bioorg Med Chem Lett. 2015 Feb 1;25(3):529-41. doi: 10.1016/j.bmcl.2014.12.026. Epub 2014 Dec 17. PubMed PMID: 25556090.

 

  1. Zabka TS, Singh J, Dhawan P, Liederer BM, Oeh J, Kauss MA, Xiao Y, Zak M, Lin T, McCray B, La N, Nguyen T, Beyer J, Farman C, Uppal H, Dragovich PS, O'Brien T, Sampath D, Misner DL. Retinal toxicity, in vivo and in vitro, associated with inhibition of nicotinamide phosphoribosyltransferase. Toxicol Sci. 2015 Mar;144(1):163-72. doi: 10.1093/toxsci/kfu268. Epub 2014 Dec 11. PubMed PMID: 25505128.

 

  1. Del Nagro C, Xiao Y, Rangell L, Reichelt M, O'Brien T. Depletion of the central metabolite NAD leads to oncosis-mediated cell death. J Biol Chem. 2014 Dec 19;289(51):35182-92. doi: 10.1074/jbc.M114.580159. Epub 2014 Oct 29. PubMed PMID: 25355314; PubMed Central PMCID: PMC4271207.

 

  1. Liang X, Yang L, Qin AR, Ly J, Liederer BM, Messick K, Ma S, Zak M, Dragovich PS, Dean BJ, Hop CE, Deng Y. Measuring NAD(+) levels in mouse blood and tissue samples via a surrogate matrix approach using LC-MS/MS. Bioanalysis. 2014 Jun;6(11):1445-57. doi: 10.4155/bio.14.8. Erratum in: Bioanalysis. 2014;6(13):1870. PubMed PMID: 25046046.

 

Products are for research use only. Not for human use.

 

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