Theshold Pharmaceuticals is a biopharmaceutical company based in South San Francisco, CA that seeks to discover and develop new therapeutics for cancer via targeting tumor hypoxia, a specific condition that occurs in most tumor microenvironments that causes low oxygen concentrations. Theshold's approach is to exploit the lack of oxygen in cancer cells as opposed to normal cells by developing Hypoxia-Activated Prodrugs (HAPs).
Its lead candidate, TH-302, which is activated preferentially under hypoxic conditions has demonstrated anticancer activity in several preclinical cancer models.
Potent and Highly Selective Hypoxia-Activated Achiral Phosphoramidate Mustards as Anticancer Drugs, J. Duan et al., Journal of Medicinal Chemistry, 51: 2412-2420, 2008.
A novel class of tubulin inhibitors that exhibit potent antiproliferation and in vitro vessel-disrupting activity, F. Meng et al., Cancer Chemotherapy and Pharmacology, 61: 953-963, 2008.
A Phase 1 dose-escalation trial of glufosfamide in combination with gemcitabine in solid tumors including pancreatic adenocarcinoma, E.G. Chiorean et al., Cancer Chemother Pharmacol (2008) 61:1019-1026.
Potent anti-tubulin tumor cell cytotoxins based on 3-aroyl indazoles, J. Duan et al., Journal of Medicinal Chemistry, 50: 1001-1006, 2007.
ARC-111 inhibits hypoxia-mediated hypoxia-inducible factor-1α accumulation, F. Meng et al., Anti-Cancer Drugs, 18: 435-445, 2007.
Glufosfamide administered using a 1-hour infusion given as first-line treatment for advanced pancreatic cancer. A phase II trial of the EORTC-new drug development group, E. Briasoulis et al., European Journal of Cancer, 39: 2334-2340, 2003.
Phase I trial of 6-hour infusion of glufosfamide, a new alkylating agent with potentially enhanced selectivity for tumors that overexpress transmembrane glucose transporters: a study of the European Organization for Research and Treatment of Cancer Early Clinical Studies Group, E. Briasoulis et al., Journal of Clinical Oncology 18: 3535-3544, 2000.