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Drug Design Lab

Virtual Drug Design

Drug design refers to the inventive process of creating new compounds and medications based on our knowledge of a biological target. Often, this biological target is a protein that may be inhibited to provide a therapeutic effect. A detailed understanding of a protein’s structure and function is often required in the design of novel inhibitors. The Mahajan laboratory utilizes virtual, or computer-aided, drug design methods to model new compounds that are complementary to a target protein’s shape and charge. These protein-inhibitor complexes are modeled on our lab’s parallel computing system and can be visualized in three-dimensions on 3D monitors, providing an in-depth view of these molecular interactions. Virtually-designed compounds are then synthesized in collaboration with Stanford’s Medicinal Chemistry Knowledge Center for testing in biochemical and cellular assays.

Drug Repositioning

The development of new drugs can cost upward of a billion dollars and take over a decade before the drug reaches the market. Drug repositioning makes use of existing drugs for the treatment of diseases where there are few therapeutic options. This approach can provide a safer alternative to the development of new compounds, since repurposed drugs are already FDA-approved, have proven bio-availabilities, and well-characterized side-effect profiles. To identify which drugs to reposition, our laboratory performs proteomic analyses of liquid biopsies (e.g. vitreous or aqueous humor) from diseased patients to identify drug targets and biomarkers. This approach allows for rapid, real-time repositioning of available drugs to patients with few therapeutic options. 

Projects

Structure-based drug design for inherited eye diseases.
Identifying available drugs to treat patients with rare diseases using proteomics.

News

Jul 26 2018 | Posted In: 20/20 Blog
San Francisco, CA — The majority of astronauts who travel in space for a prolonged period of time experience vision loss. Some vision problems are resolved after returning to earth, but others are irreversible.
Jul 12 2018 | Posted In: 20/20 Blog
Palo Alto, CA — Dr. Vinit Mahajan and Dr.
Dec 21 2017 | Stanford Report | Posted In: 20/20 Blog, Press
Researchers are studying proteins in the eye to find existing drugs that can treat a rare eye disease known as neovascular inflammatory vitreoretinopathy that causes blindness.
Dec 13 2017 | Posted In: 20/20 Blog
Using proteomics to identify new drug targets for PVR.
Jun 21 2011 | Posted In: 20/20 Blog
We recently published a paper on our experience using the Retisert implant for sympathetic ophthalmia in the Journal Ophthalmology. Implantation into the eyes of eight patients stabilized vision, provided inflammatory control, and reduced dependence on systemic immunosuppression.

Publications

Bevacizumab injection in patients with neovascular age-related macular degeneration increases angiogenic biomarkers, Cabral, Thiago, Lima Luiz H., Mello Luiz Guilherme, Polido Júlia, Correa Éverton P., Oshima Akiyoshi, Duong Jimmy, Serracarbassa Pedro, Regatieri Caio V., Mahajan Vinit B., et al. , Ophthalmology Retina, Volume 2, p.31–37, (2018)
Personalized proteomics in proliferative vitreoretinopathy implicate hematopoietic cell recruitment and mTOR as a therapeutic target, C Roybal, Nathaniel, Velez Gabriel, Toral Marcus A., Tsang Stephen H., Bassuk Alexander G., and Mahajan Vinit B. , American journal of ophthalmology, (2017)
Retinal and choroidal angiogenesis: a review of new targets, Cabral, Thiago, Mello Luiz Guilherme, Lima Luiz H., Polido Júlia, Regatieri Caio V., Belfort Rubens, and Mahajan Vinit B. , International journal of retina and vitreous, Volume 3, Number 1, p.31, (2017)
Therapeutic drug repositioning using personalized proteomics of liquid biopsies, Velez, Gabriel, Bassuk Alexander G., Colgan Diana, Tsang Stephen H., and Mahajan Vinit B. , JCI insight, Volume 2, (2017)
Ocular hypertension after intravitreal dexamethasone (Ozurdex) sustained-release implant, Chin, Eric K., Almeida David R. P., Velez Gabriel, Xu Kunyong, Peraire Maria, Corbella Maria, Elshatory Yasser M., Kwon Young H., Gehrs Karen M., H Boldt Culver, et al. , Retina, Volume 37, p.1345–1351, (2017)