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MedKoo Cat#: 407304 | Name: GNE-617
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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 Structure

GNE-617
GNE-617
CAS#1362154-70-8

Theoretical Analysis

MedKoo Cat#: 407304

Name: GNE-617

CAS#: 1362154-70-8

Chemical Formula: C21H15F2N3O3S

Exact Mass: 427.0802

Molecular Weight: 427.43

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

Price and Availability

Size Price Availability Quantity
25mg USD 250.00 2 Weeks
50mg USD 450.00 2 Weeks
100mg USD 750.00 2 Weeks
200mg USD 1,250.00 2 Weeks
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Related CAS #
No Data
Synonym
GNE-617; GNE 617; GNE617.
IUPAC/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
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
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
GNE-617 is a specific NAMPT inhibitor that inhibits the biochemical activity of NAMPT with an IC50 of 5 nM.
In vitro activity:
To test whether pharmacological NAMPT inhibition resulted in similar cytotoxicity in IDH1R132H cells to the esiRNA-mediated NAMPT knockdown, this study exposed cells to the chemically distinct, specific NAMPT inhibitors FK866, GMX1778 and GNE-617. Each inhibitor reduced the metabolic activity—quantified via the NAD(P)H-dependent WST-1-reduction rate—after 48 h of treatment in a concentration-dependent manner (Figure 5A). The IC50 values were determined to be 36.8 nM, 19.9 nM and 27.9 nM for FK866, GMX1778 and GNE-617, respectively. Reference: Int J Mol Sci. 2022 May 21;23(10):5787. https://pubmed.ncbi.nlm.nih.gov/35628596/
In vivo activity:
GNE-617 was highly efficacious and induced tumor regression within 5 days of twice daily treatment at MTDs of 10 to 15 mg/kg (20 to 30 mg/kg total dose/day) in the HCT-116 [%TGI at 15 mg/kg, twice daily = 87 (95% CI = 78, 94)], MiaPaCa-2 [%TGI at 10 mg/kg, twice daily = 91 (95% CI = 87, 95)], PC3 [%TGI at 15 mg/kg, twice daily = 168 (95% CI = 122, 476)], and HT-1080 [%TGI at 15 mg/kg, twice daily = 143 (95% CI = 107, 438)] xenograft models (Figures 1, A–D, and W2). Reference: Neoplasia. 2013 Dec;15(12):1314-29. https://pubmed.ncbi.nlm.nih.gov/24403854/
Solvent mg/mL mM
Solubility
DMF 20.0 46.79
DMSO 78.7 26.22
DMSO:PBS (pH 7.2) (1:4) 0.2 0.47
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 427.43 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Clausing M, William D, Preussler M, Biedermann J, Grützmann K, Richter S, Buchholz F, Temme A, Schröck E, Klink B. Different Effects of RNAi-Mediated Downregulation or Chemical Inhibition of NAMPT in an Isogenic IDH Mutant and Wild-Type Glioma Cell Model. Int J Mol Sci. 2022 May 21;23(10):5787. doi: 10.3390/ijms23105787. PMID: 35628596; PMCID: PMC9143996. 2. Ogino Y, Sato A, Uchiumi F, Tanuma SI. Cross resistance to diverse anticancer nicotinamide phosphoribosyltransferase inhibitors induced by FK866 treatment. Oncotarget. 2018 Mar 27;9(23):16451-16461. doi: 10.18632/oncotarget.24731. PMID: 29662658; PMCID: PMC5893253. 3. O'Brien T, Oeh J, Xiao Y, Liang X, Vanderbilt A, Qin A, Yang L, Lee LB, Ly J, Cosino E, LaCap JA, Ogasawara A, Williams S, Nannini M, Liederer BM, Jackson P, Dragovich PS, Sampath D. Supplementation of nicotinic acid with NAMPT inhibitors results in loss of in vivo efficacy in NAPRT1-deficient tumor models. Neoplasia. 2013 Dec;15(12):1314-29. doi: 10.1593/neo.131718. PMID: 24403854; PMCID: PMC3884523.
In vitro protocol:
1. Clausing M, William D, Preussler M, Biedermann J, Grützmann K, Richter S, Buchholz F, Temme A, Schröck E, Klink B. Different Effects of RNAi-Mediated Downregulation or Chemical Inhibition of NAMPT in an Isogenic IDH Mutant and Wild-Type Glioma Cell Model. Int J Mol Sci. 2022 May 21;23(10):5787. doi: 10.3390/ijms23105787. PMID: 35628596; PMCID: PMC9143996. 2. Ogino Y, Sato A, Uchiumi F, Tanuma SI. Cross resistance to diverse anticancer nicotinamide phosphoribosyltransferase inhibitors induced by FK866 treatment. Oncotarget. 2018 Mar 27;9(23):16451-16461. doi: 10.18632/oncotarget.24731. PMID: 29662658; PMCID: PMC5893253.
In vivo protocol:
1. O'Brien T, Oeh J, Xiao Y, Liang X, Vanderbilt A, Qin A, Yang L, Lee LB, Ly J, Cosino E, LaCap JA, Ogasawara A, Williams S, Nannini M, Liederer BM, Jackson P, Dragovich PS, Sampath D. Supplementation of nicotinic acid with NAMPT inhibitors results in loss of in vivo efficacy in NAPRT1-deficient tumor models. Neoplasia. 2013 Dec;15(12):1314-29. doi: 10.1593/neo.131718. PMID: 24403854; PMCID: PMC3884523.
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. 2: 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. 3: 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. 4: 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. 5: 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. 6: Oh A, Ho YC, Zak M, Liu Y, Chen X, Yuen PW, Zheng X, Liu Y, Dragovich PS, Wang W. Structural and biochemical analyses of the catalysis and potency impact of inhibitor phosphoribosylation by human nicotinamide phosphoribosyltransferase. Chembiochem. 2014 May 26;15(8):1121-30. doi: 10.1002/cbic.201402023. Epub 2014 May 5. PubMed PMID: 24797455. 7: O'Brien T, Oeh J, Xiao Y, Liang X, Vanderbilt A, Qin A, Yang L, Lee LB, Ly J, Cosino E, LaCap JA, Ogasawara A, Williams S, Nannini M, Liederer BM, Jackson P, Dragovich PS, Sampath D. Supplementation of nicotinic acid with NAMPT inhibitors results in loss of in vivo efficacy in NAPRT1-deficient tumor models. Neoplasia. 2013 Dec;15(12):1314-29. PubMed PMID: 24403854; PubMed Central PMCID: PMC3884523. 8: Shames DS, Elkins K, Walter K, Holcomb T, Du P, Mohl D, Xiao Y, Pham T, Haverty PM, Liederer B, Liang X, Yauch RL, O'Brien T, Bourgon R, Koeppen H, Belmont LD. Loss of NAPRT1 expression by tumor-specific promoter methylation provides a novel predictive biomarker for NAMPT inhibitors. Clin Cancer Res. 2013 Dec 15;19(24):6912-23. doi: 10.1158/1078-0432.CCR-13-1186. Epub 2013 Oct 4. PubMed PMID: 24097869.