RGNCY-0087 (3144 Pan-Ras inhibitor)

3144 is a multivalent PAN-RAS inhibitor shown to bind to RAS proteins.  3144 exhibited lethality in cell lines partially dependent on RAS protein expression by inducing caspase activity to a similar level as another apoptosis inducer, staurosporine.  It is metabolically stable in liver microsomes and has anti-tumor activity in xenograft mouse cancer models (MDA-MB-231 and PDTALL22 patient T-ALL sample) when administered orally or intravenously.  At high concentrations, 3144 demonstrated toxicity and off-target activity in vitro and in vivo.  3144 is an effective tool in developing pan-RAS inhibitory treatments for cancers.

Systematic Name: 3-amino-N-(3-(5-((4-(2,5-dichlorobenzyl)piperazin-1-yl)methyl)-3-(4-(trifluoromethoxy)phenyl)-1H-indol-1-yl)propyl)piperidine-4-carboxamide

SMILES:  ClC1=C(CN(CC2)CCN2CC3=CC=C4C(C(C5=CC=C(OC(F)(F)F)C=C5)=CN4CCCNC(C6CCNCC6N)=O)=C3)C=C(Cl)C=C1

Formula: C36H41Cl2F3N6O2

Mol Wt:  716.26

PMID:  28235199