4-Br-Bnlm is a selective inhibitor of glucose-regulated protein 94 (Grp94) with an EC50 value of 0.96 μM. 4-Br-Bnlm reduces the levels of mutant myocilin proteins as well as wild-type myocilin misfold in cells. 4-Br-Bnlm promotes the clearance of toxic formsof myocilin and reduces myocilin toxicity[1][2].
in vivo
4-Br-Bnlm (300 μM; eye drops; once daily for 12 weeks) clears the mutant myocilin within trabecular meshwork (TM) cells and decreases intraocular pressure (IOP) in Tg-MYOCY437H mice model. 4-Br-Bnlm improves photopic negative response (PhNR) deficits[2].
Animal Model:
Tg-MYOCY437H mice[2].
Dosage:
300 μM.
Administration:
Eye drops; once daily for 12 weeks.
Result:
Inhibited mutant myocilin expression and restored the PhNR deficits.
References
[1] Stothert AR, et al, Fontaine SN, Crowley VM, Mishra S, Blagg BS, Lieberman RL, Dickey CA. Exploiting the interaction between Grp94 and aggregated myocilin to treat glaucoma. Hum Mol Genet. 2014 Dec 15;23(24):6470-80. DOI:10.1093/hmg/ddu367 [2] Stothert AR, et al. Isoform-selective Hsp90 inhibition rescues model of hereditary open-angle glaucoma. Sci Rep. 2017 Dec 20;7(1):17951. DOI:10.1038/s41598-017-18344-4
