Glanatec (ripasudil) / Kowa - LARVOL DELTA

Therapeutic Potential of Rho Kinase Inhibitors in Corneal Disease: A Systematic Review of Preclinical and Clinical Studies. (PubMed, Biomedicines) - "Preclinical models (rabbit, porcine, human explants) uniformly showed ROCKis (Y-27632, Ripasudil, Netarsudil, H-1152) accelerate corneal endothelial cell proliferation, migration, and restoration of a hexagonal monolayer with improved barrier and pump function over days to weeks. ROCKis demonstrate consistent pro-regenerative effects on corneal endothelium in multiple models and show promising clinical efficacy in Fuchs endothelial dystrophy and pseudophakic endothelial failure. Future work should explore novel delivery systems and larger controlled trials to optimize dosing, safety, and long-term outcomes."

Journal • Preclinical • Review • Ophthalmology

Human endogenous retrovirus-K envelope protein is aberrantly expressed in serous ovarian cancer and promotes chemosensitivity via NF-κB/P-glycoprotein pathway inhibition. (PubMed, J Ovarian Res) - "HERV-K env was expressed in serous ovarian carcinoma and significantly associated with chemosensitivity. HERV-K env attenuated NF-κB/P-glycoprotein, a mechanism of chemoresistance. Hence, it could have therapeutic potential in chemoresistant ovarian cancers."

Journal • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor

DETECT I: Descemet Endothelial Thickness Comparison Trial I (clinicaltrials.gov) - P3 | N=160 | Recruiting | Sponsor: Stanford University | Trial completion date: Aug 2027 ➔ Nov 2027 | Trial primary completion date: Jul 2026 ➔ Oct 2026

Trial completion date • Trial primary completion date

Neuroprotective effect of ripasudil on retinal ganglion cells via an antioxidative mechanism. (PubMed, Jpn J Ophthalmol) - "Ripasudil may have neuroprotective effects via an antioxidative mechanism, which could be useful as an intraocular pressure-independent additive."

Journal • Glaucoma • Ophthalmology

A Case of Corneal Endothelial Cell Loss After PreserFlo MicroShunt Implantation Requiring Device Removal and Ahmed Glaucoma Valve Implantation With Tube Insertion Into the Vitreous Cavity. (PubMed, Cureus) - "After the second surgery, IOP stabilized between 10 and 14 mmHg with topical treatment, including ripasudil, and ECD remained stable at approximately 1,200 cells/mm². This case demonstrates the potential for significant and progressive ECL following PMS implantation and highlights that timely intervention with PMS removal and AGV implantation with tube insertion into the vitreous cavity can effectively stabilize ECD and achieve adequate IOP control, emphasizing the importance of close postoperative monitoring and the prompt management of complications."

Journal • Cataract • Glaucoma • Ophthalmology

Rho kinase inhibitors: a patent review (2017 - 2023). (PubMed, Expert Opin Ther Pat) - "Fasudil, ripasudil, netarsudil, and belumosudil are the primary ROCK inhibitors approved for human use. Despite some pharmacokinetic challenges, research in this field continues to advance, with significant potential for further clinical development."

Journal • Review

LINC00525 drives aggressive phenotypes in bladder cancer via YAP stabilization-mediated transcriptional activation. (PubMed, Cancer Cell Int) - "Additionally, LINC00525 inhibited YAP ubiquitination by acting on YAP lysine 321 (K321), thereby increasing its stability to prevent degradation. Through in vivo and in vitro experiments, we demonstrated the YAP-mediated promoting effect of LINC00525 on bladder cancer cells and tumor growth. Our study reveals the involvement of the LINC00525/YAP axis in regulating bladder cancer development, suggesting a potential therapeutic strategy for malignant tumors characterized by high levels of LINC00525 expression."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Targeted Protein Degradation

Liposome Encapsulation Enhances Ripasudil Therapeutic Efficacy Against Proliferative Vitreoretinal Diseases: Implications in Advanced Ocular Treatment. (PubMed, Invest Ophthalmol Vis Sci) - "These characteristics resulted in a sustained elevation of drug concentration within the ocular tissues over time. Our findings suggest that liposomal encapsulation of ripasudil supports enhanced bioavailability and effectiveness of the drug, presenting a promising innovative therapeutic approach for the treatment of proliferative vitreoretinopathy."

Journal • Age-related Macular Degeneration • Fibrosis • Immunology • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Rock-Inhibitors eyedrops preventing cataract surgery induced corneal failure in Fuchs corneal dystrophy. (PubMed, Eur J Ophthalmol) - "Endothelial cell density, polymegathism, and pleomorphism remained stable in both groups. At 9 months, Ripasudil-treated eyes continued to show stability in both BCVA and CCT, with no adverse events reported.ConclusionRipasudil demonstrated a protective effect on the corneal endothelium during cataract surgery in late-stage FCD patients, with better visual outcomes and reduced postoperative corneal edema."

Journal • Cataract • Ophthalmology

Netarsudil v/s Ripasudil: The battle of supremacy between two ROCKS-I (rho kinase inhibitors). (PubMed, Int Ophthalmol) - "Topical netarsudil 0.02% once daily was well tolerated with fewer side effects and in reducing IOP than topical ripasudil 0.4% twice daily dosing in POAG patients. Netarsudil 0.02% once daily may be considered an important option for the IOP control in POAG."

Clinical • Journal • Glaucoma • Ophthalmology • Pain

Managing pseudophakic bullous keratopathy with a topical rho kinase inhibitor: a case series. (PubMed, J Med Case Rep) - "These findings suggest that Ripasudil has potential as an effective treatment option for PBK, possibly delaying or avoiding the need for corneal transplantation. Further studies are required to confirm the long-term efficacy and safety of Ripasudil for PBK."

Journal • Cataract • Ophthalmology • Transplantation

Decoding RIG-I Ubiquitination in Fish EPC Cells: Site Identification and Antiviral Implications. (PubMed, Fish Shellfish Immunol) - "Through the integration of computational prediction with experimental validation, six ubiquitination sites (K115, K118, K145, K163, K168, and K171) were identified on RIG-I in Epithelioma papulosum cyprini (EPC) cells...It is suggested that a tunable regulatory mechanism mediated by multisite ubiquitination of RIG-I may be conserved in teleosts. These findings provide novel insights into the molecular mechanisms governing the RLR signaling pathway in teleosts, highlighting how multisite ubiquitination of RIG-I can lead to divergent antiviral outcomes."

Journal • Inflammation • Targeted Protein Degradation

Ripasudil, a Rho kinase inhibitor, attenuates testosterone-induced benign prostatic hyperplasia in rats: targeting inflammation, oxidative stress, and Rho kinase pathways. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "This study aimed to investigate the therapeutic potential of ripasudil, a Rho kinase inhibitor, and also its combination with finasteride in attenuating testosterone-induced BPH in male Wistar rats. These findings highlight the potential of ripasudil as adjunctive therapies for BPH, offering an approach for targeting inflammation, oxidative stress, and ROCK pathways. Further research is needed to clarify the underlying mechanisms driving these therapeutic effects and validate these findings in clinical settings."

Journal • Preclinical • Benign Prostatic Hyperplasia • Inflammation • Oncology • Urology • IL1B • IL6 • TGFB1 • TNFA

Rho Kinase (ROCK) Inhibitors in the Treatment of Glaucoma and Glaucoma Surgery: A Systematic Review of Early to Late Phase Clinical Trials. (PubMed, Pharmaceuticals (Basel)) - " A systematic database search was conducted in Ovid MEDLINE and Ovid Embase on 5 April 2022 using the following keywords: 'glaucoma', 'rho kinase inhibitor', 'rho-kinase inhibitor', 'rock inhibitor', 'ripasudil', 'netarsudil', and 'fasudil'. To elucidate their long-term therapeutic value and safety comprehensively, further independent, large-scale, prospective randomized controlled trials are warranted. Such studies are pivotal to augment our understanding of this emergent medication class."

Journal • Review • Cardiovascular • Glaucoma • Immunology • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain

Exploring the potential of Rho kinase inhibitors in ophthalmology: From mechanisms to clinical practice. (PubMed, Surv Ophthalmol) - "We performed a systematic database search in Ovid MEDLINE and Ovid Embase on 5th April 2022 using the following keywords: 'primary open angle glaucoma', 'glaucoma surgery', 'corneal wound healing', 'corneal endothelial dysfunction', 'diabetic retinopathy', 'diabetic macular oedema', 'age-related macular degeneration', 'rho kinase inhibitor', 'rho-kinase inhibitor', rock inhibitor', 'ripasudil', 'netarsudil' and 'fasudil'. Additionally, ROCK inhibitors show promise in enhancing endothelial cell migration, thus providing a novel treatment avenue for corneal diseases such as Fuchs endothelial dystrophy. In retinal conditions, including diabetic retinopathy and age-related macular degeneration, ROCK inhibitors reduce vascular permeability, inflammation, and fibrosis, stabilising disease progression."

Journal • Review • Age-related Macular Degeneration • Diabetic Macular Edema • Diabetic Retinopathy • Fibrosis • Glaucoma • Immunology • Inflammation • Macular Degeneration • Macular Edema • Ophthalmology • Retinal Disorders

Ponatinib and other clinically approved inhibitors of Src and Rho-A kinases abrogate dengue virus serotype 2- induced endothelial permeability. (PubMed, Virulence) - "Here, we show that the FDA-approved SFK inhibitors Bosutinib, Vandetanib and Ponatinib, as well as the ROCK inhibitors, Netarsudil and Ripasudil significantly inhibit DENV2-induced endothelial permeability. Comparable effects were observed even when ponatinib treatment was initiated after symptom onset. The results highlight ponatinib as an effective therapeutic option in severe dengue; and also a similar potential for other FDA- approved SFK and ROCK inhibitors."

Journal • Dengue Fever • Hematological Disorders • Infectious Disease • Thrombocytopenia • CDH5 • IL1B • RHOA • TNFA

Rho Kinase Inhibitors in Glaucoma Management: Current Perspectives and Future Directions. (PubMed, Drug Des Devel Ther) - "Recent clinical studies assessing the efficacy and safety of Ripasudil (K-115) and Netarsudil (AR-13324) have demonstrated promising outcomes in the treatment of various types of glaucoma. This review aims to provide an overview of ROCK inhibitors, focusing on their mechanisms of action, clinical efficacy, safety profiles, and additional benefits for eye health. Furthermore, further potential applications of ROCK inhibitors in glaucoma management are going to be discussed."

Journal • Review • Conjunctivitis • Dry Eye Disease • Glaucoma • Ocular Infections • Ocular Inflammation • Ophthalmology

AI Algorithm Aids Morphological Validation in Cell Therapy Products (ARVO 2025) - "Conclusions The AI-based algorithm demonstrated robust detection of fibroblastic changes in Ripasudil-treated EO2002 cells. Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Ophthalmology

Inhibitory effect of ripasudil on proliferative vitreoretinopathy (ARVO 2025) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Ophthalmology • Retinal Disorders • GJA1 • S100A4 • TERC

Effect of Co-Delivery of Ripasudil and Dexamethasone on Gene Expressions in Human Trabecular Meshwork Cells for Potential Prevention of Glucocorticoid-Induced Ocular Hypertension (ARVO 2025) - "However, some contradictory results in gene expression, particularly for genes like sFRP1 and WIN7B, suggest that the response to the drugs may vary depending on whether the cells are susceptible to Dex. This highlights the complexity of drug interactions and gene regulation in glaucoma treatment."

Glaucoma • Ophthalmology • ACTA2 • COL11A1 • COL1A1 • ECM2 • ROR1 • SFRP1

Descemet Stripping Only combined with Ripasudil for treating Fuchs dystrophy at a leading Center in Spain. (ARVO 2025) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Cataract • Ophthalmology

Rho kinase inhibitor liposomal therapy for preventing Fuchs endothelial corneal dystrophy progression (ARVO 2025) - "We aimed to develop eye drops containing rho kinase inhibitors (RKIs) encapsulated in liposomes conjugated with transferrin (TF receptor; upregulated biomarker in FECD) for targeting enhanced uptake by corneal endothelial cells (CECs) in FECD and compare the toxicity and efficacy of two different RKI formulations (ripasudil vs. netarsudil liposomes) to prevent FECD progression. Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Ophthalmology • COL8A2

Ripasudil does not induce phospholipid accumulation in human corneal epithelial cells. (PubMed, Exp Eye Res) - "Netarsudil, a ROCK inhibitor, is known to induce cornea verticillata as an adverse effect in clinical settings. Unlike systemic amiodarone and antimalarials, topical agents do not typically induce the development of this corneal condition...In contrast, ripasudil and Y-27632 lack these structural features. Our results suggest that ripasudil has a low likelihood of inducing cornea verticillata."

Journal • Glaucoma • Infectious Disease • Ophthalmology

Clinical implications of lowering episcleral venous pressure in the management of glaucoma and the use of Rho kinase inhibitors. (PubMed, Surv Ophthalmol) - "Regardless of the relatively modest EVP reductions achieved with current treatments, EVP lowering may have clinical significance in patients with glaucoma, particularly those with low intraocular pressure (IOP). Those who might benefit include patients with elevated EVP; normal-tension glaucoma; undergoing trabecular meshwork bypass surgery, goniotomy, or selective laser trabeculoplasty; or requiring additional IOP lowering to the low teens or with a lower-than-usual target IOP."

Journal • Review • Glaucoma • Ophthalmology

A Study to Investigate the Safety and Efficacy of K-321 Eye Drops After Simultaneous Cataract Surgery and Descemetorhexis in Participants With Fuchs Endothelial Corneal Dystrophy (FECD) (clinicaltrials.gov) - P3 | N=110 | Active, not recruiting | Sponsor: Kowa Research Institute, Inc. | Trial primary completion date: Oct 2024 ➔ Jan 2025

Trial primary completion date • Cataract • Ophthalmology • Transplantation