VNLG-152R / Isoprene Pharma - LARVOL DELTA

VNLG-152R and its deuterated analogs potently inhibit/repress triple/quadruple negative breast cancer of diverse racial origins in vitro and in vivo by upregulating E3 Ligase Synoviolin 1 (SYVN1) and inducing proteasomal degradation of MNK1/2. (PubMed, Front Oncol) - "Importantly, in direct comparison, our compounds are more effective than enzalutamide and docetaxel in achieving tumor growth inhibition/repression in the AR+ MDA-MD-453 xenograft model in mice. Collectively, our study sheds light on the involvement of SYVN1 E3 ligase in the VNLG-152R-induced degradation of MNK1/2 and the therapeutic potential of VNLG-152R and its more potent deuterated analogs as promising agents for the treatment of TNBC across diverse patient populations."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • Triple Negative Breast Cancer • AR • EIF4E • EIF4G1

Mechanistic studies on VNLG-152R-mediated tumor inhibition of triple negative breast cancer (AACR 2023) - "Inhibition of proteasomal degradation by MG-132 prior to treating cells with VNLG-152R further supports that VNLG-152R promotes SYVN1-mediated ubiquitin-proteasomal degradation of Mnk1/2. As VNLG-152R potently inhibits development and progression of TNBC of different origins by upregulating E3 ubiquitin ligase SYVN1 leading to ubiquitination and proteasomal degradation of Mnk1/2 thereby decreased oncogenic phosphorylation of eIF4E by Mnk1/2, VNLG-152R could potentially be developed for the treatment of TNBC, irrespective of racial origin."

Late-breaking abstract • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BCL2 • CCND1 • EIF4E • NUP153