FN14 antagonists and therapeutic uses thereof

摘要

The present disclosure is directed to methods of using fibroblast growth factor-inducible 14 (Fn14) antagonists to modulate activity at a TNF-like weak inducer of apoptosis (TWEAK) binding site on a cysteine-rich domain (CRD) of Fn14. The present disclosure also provides pharmaceutical compositions comprising synergistic combinations Fn14 antagonists and chemotherapeutic agents.

主权项

1. A method of inhibiting the TWEAK-Fn14 pathway in a cell, the method comprising administering to the cell an Fn14 antagonist comprising a compound of Formula (II):or a salt thereof, wherein
R1 is —H, —OH, —NH2, —N(alkyl)(alkyl), hydrocarbyl, —O-hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralkyl, heteroaryl, —O-heteroaryl, heterocyclyl, —O-heterocyclyl, halo, —OCF3, —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH2, —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), —N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH2, —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), —SO2NH2, and a vehicle, excipient, and/or carrier.