regorafenib + paxalisib + VAL-083 + VT1021 + troriluzole + ADI-PEG 20 + AZD1390

This drug is a **combination therapy** consisting of the following investigational and approved agents, each with a distinct and often novel mechanism of action relevant primarily to oncology (especially brain cancers like glioblastoma and other solid tumors): - **Regorafenib**: a small molecule multi-kinase inhibitor that blocks multiple protein kinases involved in tumor angiogenesis (VEGFR1-3, TIE2), oncogenesis (KIT, RET, BRAF, RAF-1), and the tumor microenvironment (PDGFR-α/β, FGFR1/2). Approved for metastatic colorectal cancer, gastrointestinal stromal tumors, and hepatocellular carcinoma[1][3][5][7]. - **Paxalisib**: an oral, brain-penetrant selective inhibitor of phosphoinositide 3-kinase (PI3K, specifically PI3Kα) and the mammalian target of rapamycin (mTOR), in development for glioblastoma and other brain metastases. - **VAL-083 (dianhydrogalactitol)**: a bifunctional DNA-targeting agent that alkylates and cross-links DNA at N7-guanine, inducing double-strand breaks; under study for glioblastoma, ovarian cancer, and other tumors. - **VT1021**: a cyclic peptide that induces the expression of thrombospondin-1 (TSP-1) in the tumor microenvironment, which then acts on CD36 and CD47 to promote tumor and endothelial cell apoptosis and immune modulation. In development for glioblastoma and solid tumors[2][4][6][8]. - **Troriluzole**: a prodrug of riluzole that modulates glutamatergic neurotransmission by inhibiting glutamate release; investigated for glioma and neurodegenerative diseases. - **ADI-PEG 20 (pegargiminase)**: a pegylated arginine deiminase enzyme that depletes arginine, inhibiting growth of arginine-auxotrophic cancers such as glioblastoma and other solid tumors. - **AZD1390**: a selective, brain-penetrant inhibitor of ataxia telangiectasia mutated (ATM) kinase, which is a key regulator of the cellular DNA damage response, developed to radiosensitize gliomas and other solid tumors. This combination is designed to target multiple complementary cancer pathways—kinase signaling, DNA damage, immunosuppression, neurotransmission, metabolic dependency, and DNA damage repair—to overcome resistance and improve outcomes in aggressive or refractory tumors.

Other names

dianhydrogalactitolpegargiminase