GNE-495
featured

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

MedKoo CAT#: 522457

CAS#: 1449277-10-4

Description: GNE-495 is a potent and selective MAP4K4 Inhibitor with efficacy in retinal angiogenesis. GNE-495 showed excellent potency and good PK and was used to demonstrate in vivo efficacy in a retinal angiogenesis model recapitulating effects that were observed in the inducible Map4k4 knockout mice. Mitogen-activated protein kinase kinase kinase kinase (MAP4K4, or HGK), and its homologues Misshapen and MIG-15 have been shown to regulate a multitude of biological processes, including embryonic development,metabolism, inflammation, neural regeneration, angiogenesis, and cancer.

Chemical Structure

img
GNE-495
CAS# 1449277-10-4
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 522457
Name: GNE-495
CAS#: 1449277-10-4
Chemical Formula: C22H20FN5O2
Exact Mass: 405.16
Molecular Weight: 405.430
Elemental Analysis: C, 65.18; H, 4.97; F, 4.69; N, 17.27; O, 7.89

Price and Availability

Size Price Availability Quantity
5mg USD 90 Ready to ship
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2650 Ready to ship
Bulk inquiry

Synonym: GNE-495; GNE 495; GNE495.

IUPAC/Chemical Name: 8-amino-N-(1-(cyclopropanecarbonyl)azetidin-3-yl)-2-(3-fluorophenyl)-1,7-naphthyridine-5-carboxamide

InChi Key: FYXCIBJXJYBWPX-UHFFFAOYSA-N

InChi Code: InChI=1S/C22H20FN5O2/c23-14-3-1-2-13(8-14)18-7-6-16-17(9-25-20(24)19(16)27-18)21(29)26-15-10-28(11-15)22(30)12-4-5-12/h1-3,6-9,12,15H,4-5,10-11H2,(H2,24,25)(H,26,29)

SMILES Code: O=C(C1=C2C=CC(C3=CC=CC(F)=C3)=NC2=C(N)N=C1)NC4CN(C(C5CC5)=O)C4

Appearance: Yellow 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:

Biological target: GNE-495 is a MAP4K4 inhibitor with an IC50 of 3.7 nM.
In vitro activity: Consistent with the good permeability properties, these compounds exhibited adequate potency preventing migration of HUVEC cells in vitro, an assay that is used to evaluate antiangiogenic behavior. Notably, compound 13 (GNE-495) showed the best balance of MAP4K4 inhibition, permeability, microsomal stability, and cellular potency. Reference: ACS Med Chem Lett. 2015 Aug 13; 6(8): 913–918. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4538449/
In vivo activity: In order to determine if compound 13 (referred to as GNE-495 herein) can inhibit MAP4K4 function in vivo, this study utilized the neonatal retinal vascular development model because inducible knockout of Map4k4 inhibited retinal vascular outgrowth and altered retinal vascular morphology. IP injection of GNE-495 into newborn mice dose-dependently delayed retinal vascular outgrowth (Figures 3A,B and S3) and induced abnormal retinal vascular morphology (Figure 3C,D). These phenotypes recapitulated the retinal vascular defects observed in the inducible Map4k4 knockout mice, indicating that GNE-495 is indeed active in vivo. It is important to note that though GNE-495 also inhibits the related kinases MINK and TNIK, the observed in vivo effects were attributable solely to MAP4K4 inhibition as has been shown previously. Reference: ACS Med Chem Lett. 2015 Aug 13; 6(8): 913–918. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4538449/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 3.6 8.85
DMSO:PBS (pH 7.2) (1:7) 0.1 0.31
DMF 5.0 12.33
Water 1.0 2.47

Preparing Stock Solutions

The following data is based on the product molecular weight 405.43 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. Ndubaku CO, Crawford TD, Chen H, Boggs JW, Drobnick J, Harris SF, Jesudason R, McNamara E, Nonomiya J, Sambrone A, Schmidt S, Smyczek T, Vitorino P, Wang L, Wu P, Yeung S, Chen J, Chen K, Ding CZ, Wang T, Xu Z, Gould SE, Murray LJ, Ye W. Structure-Based Design of GNE-495, a Potent and Selective MAP4K4 Inhibitor with Efficacy in Retinal Angiogenesis. ACS Med Chem Lett. 2015 Jun 29;6(8):913-8. doi: 10.1021/acsmedchemlett.5b00174. PMID: 26288693; PMCID: PMC4538449.
In vitro protocol: 1. Ndubaku CO, Crawford TD, Chen H, Boggs JW, Drobnick J, Harris SF, Jesudason R, McNamara E, Nonomiya J, Sambrone A, Schmidt S, Smyczek T, Vitorino P, Wang L, Wu P, Yeung S, Chen J, Chen K, Ding CZ, Wang T, Xu Z, Gould SE, Murray LJ, Ye W. Structure-Based Design of GNE-495, a Potent and Selective MAP4K4 Inhibitor with Efficacy in Retinal Angiogenesis. ACS Med Chem Lett. 2015 Jun 29;6(8):913-8. doi: 10.1021/acsmedchemlett.5b00174. PMID: 26288693; PMCID: PMC4538449.
In vivo protocol: 1. Ndubaku CO, Crawford TD, Chen H, Boggs JW, Drobnick J, Harris SF, Jesudason R, McNamara E, Nonomiya J, Sambrone A, Schmidt S, Smyczek T, Vitorino P, Wang L, Wu P, Yeung S, Chen J, Chen K, Ding CZ, Wang T, Xu Z, Gould SE, Murray LJ, Ye W. Structure-Based Design of GNE-495, a Potent and Selective MAP4K4 Inhibitor with Efficacy in Retinal Angiogenesis. ACS Med Chem Lett. 2015 Jun 29;6(8):913-8. doi: 10.1021/acsmedchemlett.5b00174. PMID: 26288693; PMCID: PMC4538449.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1. Ndubaku CO, Crawford TD, Chen H, et al. Structure-Based Design of GNE-495, a Potent and Selective MAP4K4 Inhibitor with Efficacy in Retinal Angiogenesis. ACS Med Chem Lett. 2015;6(8):913–918. Published 2015 Jun 29. doi:10.1021/acsmedchemlett.5b00174