PLURIPOTENT EPIGENETIC REGULATOR OBP-801

 

OBP-801 (also known as YM753) is a novel histone deacetylase (HDAC) inhibitor developed by Oncolys BioPharma for potential anticancer treatment, demonstrating effects like inducing cell death (apoptosis) and halting cancer cell growth in various cancers, including lung, breast, and brain tumors, often synergistically with other drugs, by interfering with HDAC enzymes crucial for cancer progression. It works by inhibiting HDACs, leading to gene expression changes that trigger cancer cell death.

OBP-801 has been studied in animal glaucoma models and found to improve the survival of filtering blebs.

Koga and colleagues have demonstrated the anti-fibrotic effect of OBP-801 (OBP) on filtering blebs in a rabbit glaucoma filtration surgery (GFS) model, as well as rabbit eyes which underwent PRESERFLO microshunt implantation surgery (PMS).

The second study involved 19 Japanese white rabbits that underwent PMS in the right eye, with those eyes divided into 3 groups: (1) intraoperative subconjunctival injection of 0.02% mitomycin-C (MMC) (n = 6), (2) postoperative instillation of 100 nM OBP eye drops (n = 7), or (3) a balanced salt solution (BSS) control (n = 6). 

Bleb morphology and IOP were monitored for 12 weeks postoperative, with the bleb tissues then undergoing evaluation of fibrosis and Western blot analysis. 

A lower postoperative IOP was maintained in the OBP-group eyes, and at 12 weeks postoperative, the IOP was significantly lower in that group than in the BSS and MMC groups (p < 0.01). 

OBP-treated eyes showed no adverse effects and reduced levels of alpha-smooth muscle actin and collagen deposition, thus suggesting that OBP is a promising candidate for improving surgical outcomes post PMS.

Yamamoto et al have also studied the effect of OBP in rabbit eyes with GFS. They found OBP treatment involving subconjunctival injection or eye drops showed no adverse effects, and reduced levels of α-SMA and collagen deposition at the surgical wound site. OBP maintained the long-lived bleb without scar formation, and IOP was lower at 30 postoperative days compared with the vehicle control group. These findings suggest that OBP is an effective and useful candidate low-molecular-weight agent for improving wound healing and surgical outcomes in a rabbit model of GFS.

REFERENCES:

1. Koga, Y., Ikushima, T., Hiramoto, N. et al. Pluripotent epigenetic regulator OBP-801 attenuates fibrosis and maintains lower intraocular pressure in a rabbit PRESERFLO MicroShunt surgery model. Sci Rep (2025). https://doi.org/10.1038/s41598-025-34244-4.
2. Yamamoto Y, Mukai A, Ikushima T, Urata Y, Kinoshita S, Hamuro J, Ueno M, Sotozono C. Pluripotent epigenetic regulator OBP-801 maintains filtering blebs in glaucoma filtration surgery model. Sci Rep. 2020 Dec 1;10(1):20936. doi: 10.1038/s41598-020-77811-7. PMID: 33262357; PMCID: PMC7708845.