OGT 2115 is a potent, cell-permeable, and orally active heparanase inhibitor with an IC50 of 0.4μM[1]. OGT 2115 reduces the levels of type I interferon, decreases NF-κB nuclear translocation, blocks the spread of herpes simplex virus type 1 (HSV-1), and ultimately clears the virus[2]. OGT 2115 has been widely used to prevent dengue virus NS1 protein from disrupting the endothelial glycocalyx and altering vascular permeability[3].
In vitro, OGT 2115 treatment for 72 hours significantly inhibited the viability of PC-3 cells and DU-145 cells, with IC50 values of 18.4µM and 90.6µM, respectively[4]. Treatment with 20µM OGT 2115 combined with paclitaxel (100µM) for 48 hours reduced the viability of MDA-MB-231 cells by increasing extracellular ATP concentration and activating purinergic receptors[5]. Incubation with 10µM OGT 2115 for 12 hours reduced the level of viral protein glycoprotein D (gD) in VK2 cells and inhibited herpes simplex virus type 2 (HSV-2) replication[6].
In vivo, OGT 2115 treatment via subcutaneous injection at a dose of 15mg/kg 6 hours before Cl2 exposure alleviated Cl2-induced hypoxemia and reduced pulmonary edema in mice[7]. Daily subcutaneous injection of OGT 2115 at a dose of 10mg/kg for 4 consecutive weeks improved blood glucose levels and insulin secretion, and reduced apoptosis of pancreatic β cells in diabetic mice[8].
References:[1] Courtney S M, Hay P A, Buck R T, et al. Furanyl-1, 3-thiazol-2-yl and benzoxazol-5-yl acetic acid derivatives: novel classes of heparanase inhibitor[J]. Bioorganic & medicinal chemistry letters, 2005, 15(9): 2295-2299.
[2] Agelidis A M, Hadigal S R, Jaishankar D, et al. Viral activation of heparanase drives pathogenesis of herpes simplex virus-1[J]. Cell reports, 2017, 20(2): 439-450.
[3] Puerta-Guardo H, Glasner D R, Harris E. Dengue virus NS1 disrupts the endothelial glycocalyx, leading to hyperpermeability[J]. PLoS pathogens, 2016, 12(7): e1005738.
[4] Li X, Xu S J, Jin B, et al. Heparanase inhibitor OGT 2115 induces prostate cancer cell apoptosis via the downregulation of MCL‑1[J]. Oncology Letters, 2024, 27(2): 83.
[5] Manouchehri J M, Datta J, Marcho L M, et al. The role of heparan sulfate in enhancing the chemotherapeutic response in triple-negative breast cancer[J]. Breast Cancer Research, 2024, 26(1): 153.
[6] Hopkins J, Volety I, Qatanani F, et al. Heparanase 2 modulation inhibits HSV-2 replication by regulating heparan sulfate[J]. Viruses, 2024, 16(12): 1832.
[7] Zhang Y, Xu F, Guan L, et al. Histone H4 induces heparan sulfate degradation by activating heparanase in chlorine gas-induced acute respiratory distress syndrome[J]. Respiratory Research, 2022, 23(1): 14.
[8] Song W Y, Jiang X H, Ding Y, et al. Inhibition of heparanase protects against pancreatic beta cell death in streptozotocin‐induced diabetic mice via reducing intra‐islet inflammatory cell infiltration[J]. British Journal of Pharmacology, 2020, 177(19): 4433-4447.