Discovery of N-(thiazol-2-yl) Furanamide Derivatives as Potent Orally Efficacious AR Antagonists with Low BBB Permeability.

Quinoline clubbed triazole hybrids as VEGFR-2 targeted anticancer agents: synthesis, molecular modeling, and biological evaluation

In Silico Evaluation of 1-(Indolin-1-yl) Ethan-1-One Derivatives as Novel TRIM24 Inhibitors for Prostate Cancer

Novel benzofuran-1,3,4-thiadiazole aryl urea hybrids as dual VEGFR-2/BRAF inhibitors: anticancer activity, apoptosis induction, and molecular modeling studies.

A novel series of benzofuran-based aryl urea derivatives incorporating a 1,3,4-thiadiazole linker were designed as dual VEGFR-2/BRAFWT inhibitors using sorafenib as a pharmacophoric template, with compound 7j emerging as the most active analogue.

Striking two targets with one scaffold via benzo[d]imidazole-isatin conjugates as potent dual VEGFR-2/c-MET antagonists.

A series of benzo[d]imidazole-isatin hybrids (4a-d, 6a-d, and 8a-d) was developed and synthesized as prospective dual inhibitors of VEGFR-2 and c-MET to address tumor growth and resistance-related signaling pathways. The biological assessment demonstrated encouraging dual kinase inhibitory action, with compound 8b identified as the most balanced inhibitor, displaying IC50 values of 92 nM and 63 nM against VEGFR-2 and c-MET, respectively. In-vitro antiproliferative evaluation against MDA-MB-231 and A549 cancer cell lines revealed notable cytotoxicity for compound 8b, yielding IC50 values of 2.37 μM and 1.79 μM, respectively, exceeding the efficacy of the reference medication sunitinib. Additionally, 8b exhibited a favorable selectivity profile for normal MCF-10A cells. Mechanistic studies demonstrated that 8b caused substantial G2/M cell cycle arrest and facilitated apoptosis in MDA-MB-231 cells. Biomarker studies revealed a reduction in VEGF-A, MMP-9, and Bcl-2 levels, alongside an increase in Bax and Caspase-3, suggesting potential anti-angiogenic and pro-apoptotic characteristics in-vitro. Molecular docking analyses provided supporting models for the identified biological activities and exhibited advantageous binding interactions within both kinase active sites. These data collectively suggest that chemical 8b may serve as a promising candidate for further anticancer research.

Design, synthesis and evaluation of benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one derivatives as novel MTA cooperative PRMT5 inhibitors for the treatment of MTAP-deleted cancers.

Compound 9u exhibited significant antiproliferative activity in MTAP-deleted HCT116 cancer cells, with an IC50 value of 13 nM, exhibiting 70-fold selectivity over MTAP wild type HCT116 cells, and 9u displayed robust efficacy across diverse MTAP-deleted cancer cell lines, achieving IC50 values of <1.5-51 nM.

VEGFR-2 as a druggable target: recent advances (2025) in the development of five-membered heterocyclic anticancer agents.

The global burden of cancer continues to escalate, with angiogenesis representing a critical driver of tumor progression and metastasis. Vascular endothelial growth factor receptor-2 (VEGFR-2) stands as the principal mediator of angiogenic signaling, making it an established and compelling therapeutic target. Despite the clinical success of first-generation inhibitors, their long-term efficacy remains limited by off-target toxicities, suboptimal pharmacokinetic profiles, and the inevitable emergence of drug resistance through multiple adaptive mechanisms. These limitations underscore an urgent need for next-generation inhibitors engineered with enhanced selectivity, improved safety margins, and the capacity to circumvent resistance pathways. This comprehensive review systematically examines recent advances in the rational design, synthesis, and biological evaluation of five-membered heterocyclic scaffolds, thiadiazol, oxazole, thiazole, and pyrrole, as well as pyrazole and imidazole-based inhibitors as novel VEGFR-2 inhibitors. Each section analyzes the molecular hybridization strategies employed to integrate essential pharmacophoric features, including heteroaromatic hinge-binding motifs, hydrogen bond donor-acceptor systems for DFG motif engagement, and terminal hydrophobic groups for allosteric pocket occupancy. Detailed structure-activity relationship discussions elucidate how substituent variations influence potency, selectivity, and physicochemical properties.