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In-silico designing of novel inhibitors of rho-GTPase activating protein for treatment of glaucoma

Li Yin, Jing Zhu, Xun Bao, Yong Yao

Increased intraocular pressure resulting in the optical neuropathy characterised by permanent blindness is called glaucoma. The aqueous humor accumulates in the posterior chamber because of the slower release rate of aqueous humour as compared to the rate of its formation results in increased intraocular pressure, which creates pressure against the optic nerve causing the death of nerve cells. In 2010 more than 60.5 million individuals are affected by glaucoma and it is also the worldwide leading cause of irreversible blindness. Multiple population-based surveys estimated that about 80 million peoples would be affected by the year 2020. Earlier it is shown that the in-vitro and ex-vitro inhibition of Rho pathway by specific inhibitors causes the contractile tone relaxation of the cells which are actively involved in the aqueous outflow pathway, thus reduces intraocular pressure by increasing aqueous outflow. Thus in this research paper in-silico techniques are used to develop Rho GTPase protein inhibitors for treatment of glaucoma and it is predicted that ZINC17465958 and ZINC05124957 molecules are potent inhibitors of the Rho GTPase protein. These molecules will prove to be promising lead compound for further structure based discovery of drugs for treatment of glaucoma as they are having very good pharmacokinetic properties without presence of any toxic effects.