Uses
(5Z)-5-(5-Chloro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)-4-oxo-2-thioxo-3-thiazolidinepropanoic Acid is used in the preparation of substituted isatinylidenerhodanines. BCL6 inhibitor, an anticancer agent.
Definition
ChEBI: FX1 is a member of the class of oxindoles that is 5-chloro-oxindole in which the methylene hydrogens at position 3 have been replaced by an N-(2-carboxyethyl)rhodanin-5-ylidene group. It has a role as an antineoplastic agent. It is a member of oxindoles, an organochlorine compound, a thiazolidinone and a monocarboxylic acid. It is functionally related to a 3-methyleneoxindole and a rhodanine.
Biochem/physiol Actions
FX1 is a BCL6 inhibitor that effectively blocks BCL6 N-terminal BTB domain-mediated corepressors chromosome recruitment (by 61-87%/SMRT and 67-82%/BCOR; 50 μM FX1 for 30 min) and selectively suppresses BCL6-depenent growth (GI50 16-54 μM; >125 μM against BCL6-independent cells) in diffuse large B cell lymphoma (DLBCL) cultures, exhibiting greater affinity than its structure analog 79-6 or BCL6 corepressor SMRT for BTB domain (KD = 7 μM/FX1, 30 μM/SMRT, 129 μM/79-6). FX1 shows greater efficacy than 79-6 in reversing BCL6/corepressors-mediated target genes repression in vitro (IC50 = 35 μM vs. 318 μM with 79-6 by HEK293T-based reporter assay) and in suppressing OCI-Ly7 DLBCL xenograft tumor growth mice in vivo (100% vs. 45% suppression with respective compound via 25 mg/kg/day i.p.).
