SRI International is a long-time contractor of the NCI; one of its projects included the synthesis of compounds in the NCI Carcinogen Repository, along with preclinical development.
For both government and private clients, SRI can discover new molecular targets and novel lead compounds, develop novel models for testing in vitro and in vivo efficacy, identify mechanisms of action, optimize leads, and create cost-effective syntheses, Dr. Moos says.
Some marketed and clinical-stage cancer drugs developed at SRI include Targretin®, a retinoid receptor ligand marketed by Eisai; tirapazamine, a hypoxic tissue-selective cytotoxin; TAS-108, a selective estrogen receptor modulator licensed to Taiho Pharmaceuticals; and PDX, an improved methotrexate being developed by Allos Therapeutics.
Two drugs in preclinical studies are: SR16157, a dual-acting sulphatase inhibitor and selective estrogen receptor modulator for the treatment of breast cancer, and SR13688, an oral drug that inhibits the oncoprotein AKT. SR13688, a natural compound derived from broccoli, is nontoxic and nonmutagenic at high doses, Dr. Moos notes.
“A natural product derivative may be safer than xenobiotics used in the past and present,” says Dr. Moos. AKT, an increasingly important clinical target, is overexpressed in a variety of human cancers, where it makes tumors resistant to chemotherapy and radiation.
SRI International also has a long history of moving drugs for infectious diseases forward, Dr. Moos reports. The first drug that SRI ever helped to send to market was halofantrine, an antimalarial compound.
In late 2007, the National Institute of Allergy and Infectious Diseases (NIAID) awarded SRI $15.5 million to develop a broadly based screening program for infectious diseases, including HIV and AIDS. SRI will provide preclinical services for new therapeutics, including toxicology and pharmacology screening.
“We work with NIAID, not only in drug discovery,” elaborates Dr. Moos, “but also to make new formulations and do clinical manufacturing to get drugs to the clinic.”
SRI’s infectious disease work also caught the attention of the Department of Defense. Programs are under way to speed the manufacturing of new vaccines and therapies for natural threats like bird flu and man-made biothreats.