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Bis-Indole Drug Discovery in Multiple Therapeutic Areas
SRI is identifying candidates for advanced therapies in multiple disease areas by developing compounds from synthetically optimized, natural dietary products.
SRI’s novel bis-indole drug platform has been created by synthetically optimizing active components in natural products shown to be effective as treatments for multiple diseases. Because the bis-indoles were the derivatives of dietary component found in cruciferous vegetables, such as cabbages and broccoli, the chemicals have an excellent safety profile and are orally bioavailable. The drug platform was discovered by Dr. Ling Jong, senior program director of medicinal chemistry in SRI’s Center for Cancer and Metabolism.
SRI researchers have moved drug candidates derived from the bis-indole platform from the laboratory to clinical testing. Through collaboration with the National Cancer Institute, SR13668, which inhibits the Akt pathway, has advanced to human clinical trials for cancer prevention. Having demonstrated the value of the drug platform in the treatment and prevention of various cancers, SRI researchers are now exploring its potential in treating infectious and neurodegenerative diseases.
SRI has identified new bis-indole analogues that have broad-spectrum antibacterial activity against several gram-positive and gram-negative bacteria, as well as multidrug-resistant strains, such as hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA). One optimized drug lead, SRI-011225, appears to have a distinct mechanism of action from known classes of antibiotics, based on mechanistic studies and the lack of cross-resistance with other classes of antimicrobials. Thus, SRI-011225 is of interest in the commercial pharmaceutical market for resistant hospital-acquired infections.