UCI-14

UCI-14 is a gltA1/lprQ modulator with in vitro anti-tuberculosis activity against drug-sensitive and multidrug-resistant mycobacteria. UCI-14 upregulates the expression of genes encoding citrate synthase I, downregulates the expression of genes encoding conserved mycobacterial lipoprotein, and alters the carbon metabolism of mycobacteria. UCI-14 reactivates the expression of wild-type p53 target genes in p53 -mutated cells. UCI-14 can be used in the research of tuberculosis and cancer ^{[1] [2]}.

In Vitro, UCI-14 exhibits in vitro antitubercular activity with a consistent MIC of 12.4 µM against drug-sensitive Mycobacterium tuberculosis H37Rv strain and clones 2-3, and MDR Mycobacterium tuberculosis CIBIN:UMF:15:99 strain and clones 1-3, while H37Rv clone 1 shows a higher MIC of 24.8 µM^[1]. UCI-14 (12.4-24.8 µM; 4 h) significantly increases gltA1 expression and decreases lprQ expression in drug-sensitive Mycobacterium tuberculosis H37Rv clones, while causing no significant gene expression changes in MDR Mycobacterium tuberculosis CIBIN:UMF:15:99 clones^[1]. UCI-14 activates a subset of genes overlapping with wild-type p53 targets in p53-null Saos-2 cells expressing mutant p53 (G245S), as well as in TOV-112D cells with endogenous p53 mutations, with 116 overlapping targets identified in transcriptomic profiling^[2].

References:
[1]. Penuelas-Urquides K, et al. Two New Dihydrosphingosine Analogs Against Mycobacterium tuberculosis Affect gltA1, lprQ, and rpsO Expression. Front Microbiol. 2021;12:742867.
[2]. Law F, et al. Second-Site Rescue Mutants as Tools to Uncover Reactivation Mechanisms of p53 Cancer Mutants. Department of Biological Chemistry, Chao Family Comprehensive Cancer Center, University of California, Irvine; 2025.