4-Br-Bnlm, with an EC 50 of 0.96 µM, acts as a selective inhibitor of glucose-regulated protein 94 (Grp94). It effectively reduces both mutant and wild-type misfolded myocilin proteins in cells, thereby enhancing the clearance of toxic forms of myocilin and diminishing myocilin toxicity [1] [2].

4-Br-Bnlm, when applied at concentrations ranging from 0 to 100 µM for 24 hours, inhibited the expression of 1477N mutant myocilin in human embryonic kidney (HEK) cells [1]. At 30 µM over 24 hours, it reduced the levels and toxicity of mutant myocilin in primary human trabecular meshwork (HTM) cells [1]. Additionally, 4-Br-Bnlm at concentrations of 3, 10, and 30 µM for 24 hours inhibited myocilin secretion in a dose-dependent manner [1]. The application of 4-Br-Bnlm at 30 µM and 100 µM for 24 hours did not induce a heat shock response in HTM cells [2]. In a cell viability assay with primary human HTM cells, using a concentration of 30 µM for 24 hours, 4-Br-Bnlm significantly reduced the level of Y437H mutant myocilin without affecting wild-type myocilin and the RFP vector in HEK cells. Western blot analysis with HEK cells across a concentration range of 0, 1, 3, 10, 30, and 100 µM over 24 hours showed a significant decrease in 1477N mutant myocilin expression without degrading other Hsp90-dependent clients, Akt and Ras.

Administering 4-Br-Bnlm at a dosage of 300 µM via eye drops once daily for 12 weeks effectively cleared mutant myocilin from trabecular meshwork cells and reduced intraocular pressure in Tg-MYOC Y437H mouse models. Additionally, 4-Br-Bnlm improved photopic negative response (PhNR) deficiencies [2]. Animal Model: Tg-MYOC Y437H mice [2].