GNE684

GNE684 is a potent inhibitor of potent receptor interacting protein 1 (RIP1), with mean Kiapp values of 21 nM, 189 nM and 691 nM for human mouse and rat RIP1, respectively.

Product information

Molecular Weight: 432.48

Formula: C23H24N6O3

Chemical Name: (5S)-N-[(3S)-7-methoxy-1-methyl-2-oxo-1H, 2H, 3H, 4H, 5H-pyrido[3, 4-b]azepin-3-yl]-5-phenyl-5H, 6H, 7H-pyrrolo[1, 2-b][1, 2, 4]triazole-2-carboxamide

Smiles: CN1C2=CN=C(C=C2CC[C@H](NC(=O)C2N=C3CC[C@@H](C4C=CC=CC=4)N3N=2)C1=O)OC

InChiKey: JXFYROJRZJPKTQ-IRXDYDNUSA-N

InChi: InChI=1S/C23H24N6O3/c1-28-18-13-24-20(32-2)12-15(18)8-9-16(23(28)31)25-22(30)21-26-19-11-10-17(29(19)27-21)14-6-4-3-5-7-14/h3-7,12-13,16-17H,8-11H2,1-2H3,(H,25,30)/t16-,17-/m0/s1

Technical Data

Appearance: Solid Power

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

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

GNE684 (20 μM; 20 hours) inhibits RIP1 kinase driven cell death effectively in several human and mouse cell lines. GNE684 (20 μM; 0-60 minutes) disrupts TBZ (2 μM BV6, 20 ng/ml TNF, 20 μM zVAD)-induced RIP1 autophosphorylation, interactions between RIP1 and RIP3, RIP3 autophosphorylation, and phosphorylation of MLKL by RIP3.

In Vivo:

GNE684 also had no impact on overall survival or tumor growth in the KPP or KPR (LSL-Kras G12D/+; p16/p19 fl/wt ; Trp53 R270H/wt ; Pdx1-cre) PDAC models. GNE684 (50mg/kg; p.o. twice daily) inhibits colitis and ileitis caused by NEMO deficiency in intestinal epithelial cells (IECs).

References:

1. Patel S, et al. RIP1 inhibition blocks inflammatory diseases but not tumor growth or metastases. Cell Death Differ. 2019 May 17.

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