Delving into the Latest Updates on Ripasudil Hydrochloride Hydrate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Ripasudil, Ripasudil hydrochloride hydrate (JAN), Ripasudil hydrocholoride hydrate

+ [5]

Target

ROCK

Mechanism

ROCK inhibitors(Rho-associated kinases inhibitors)

Therapeutic Areas

Eye DiseasesCongenital DisordersOther Diseases

Active Indication

GlaucomaOcular HypertensionFuchs' Endothelial Dystrophy+ [2]

Inactive Indication-

Originator Organization

Kowa Co., Ltd.

Active Organization

Kowa Research Institute, Inc.

Kowa Pharmaceuticals America, Inc.

Kowa Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

JP (26 Sep 2014),

GlaucomaOcular Hypertension

Regulation-

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Structure/Sequence

Molecular FormulaC15H21ClFN3O3S

InChIKeyDRZAXKMMRYEBQP-IDMXKUIJSA-N

CAS Registry887375-67-9

View All Structures (2)

PURPOSEEffect of topical administration of a Rho kinase inhibitor, ripasudil, on epithelial wound healing in a mouse cornea was investigated. Effects of treatment of cultured human corneal epithelial cell (HCEC) line and organ-cultured corneal epithelium with ripasudil on expression of p-ERK was also examined.METHODSEpithelial defects with a diameter of 2.0 mm were prepared in the central corneas of C57BL/6 mice with or without 1-week travoprost pre-treatment, to which ripasudil or PBS as a control was instilled every 6 h immediately after preparation. The mice eyes were cultured with or without travoprost for 24-hrs. The expression levels of p-ERK in epithelium of mice eyes were compared by immunostaining after further 24-hrs culture with or without ripasudil for 24-hrs. HCEC were cultured with or without ripasudil and processed for examination for proliferation activity and protein expression of p-ERK by either immunostaining or Western blotting. The cells were also treated with or without travoprost for 24-hrs, and were further cultured with or without ripasudil. Expression levels of p-ERK were examined by Western blotting.RESULTSRipasudil treatment suppressed post-debridement epithelial healing in association with reduced proliferation activity in peripheral (limbal) epithelium in cornea with or without pre-treatment with travoprost. Ripasudil treatment accelerated p-ERK expression. Ripasudil supplementation upregulated proliferation with increased p-ERK in HCEC.CONCLUSIONRipasudil treatment promotes wound healing of the mouse corneal epithelium by enhancing cell proliferation on peripheral (limbal) epithelium.

01 Dec 2024·Canadian Journal of Ophthalmology

In vivo confocal microscopy findings after Descemet stripping only with and without topical ripasudil supplementation in Fuchs endothelial dystrophy

Article

Author: Moloney, Gregory ; Devasahayam, Raj N ; Oliver, Cameron ; Burgos-Blasco, Barbara ; Northey, Luke C ; Trinh, Tanya

OBJECTIVETo report corneal epithelial and corneal endothelial cell (CEC) changes following Descemet stripping only (DSO) with and without topical ripasudil using in vivo confocal microscopy (IVCM).METHODSProspective interventional case series of patients who underwent DSO for Fuchs endothelial dystrophy with or without postoperative topical ripasudil (4%, 6 times per day). Patients underwent IVCM (ConfoScan 3; NIDEK Technologies, Padova, Italy) at baseline, monthly until corneal clearance, and then every 6 months. En face images were obtained of the epithelium, anterior and posterior corneal stroma, and endothelium of the central and superior cornea. The epithelial and endothelial layer images were evaluated qualitatively.RESULTSIVCM imaging was obtained from 34 patients, 26 (76%) of whom were supplemented with ripasudil and 8 (24%) of whom were not. Two eyes (6%) did not clear and required a keratoplasty. IVCM confirmed epithelial and endothelial cell morphology changes and reestablishment of a CEC mosaic. Hyperreflective nuclei, pleomorphism, multinucleated cells, and pseudoguttae were identified within the descemetorhexis. In patients on ripasudil, epithelial cells demonstrated transition from stratified squamous to spindle cell shape in regions of ripasudil-induced honeycomb edema. Migrating cells adopted an amoeboid shape and cytoplasm elongation when crossing to central stroma. Transient epithelial cell morphology changes and endothelial cell amoeboid shape changes appear to be uniquely associated with ripasudil. Rarely, figures were noted in both ripasudil-treated and non-ripasudil-treated corneas that resembled mitotic bodies.CONCLUSIONSCECs display a range of adaptive mechanisms during healing to re-form the endothelial mosaic following DSO. Ripasudil administration appears to induce unique epithelial and endothelial cell changes.

01 Dec 2024·BMJ Case Reports

Ripasudil’s paradox: bullous keratopathy with honeycomb twist

Article

Author: Pattebahadur, Rajesh ; Singh, Kanishk ; Snehi, Sagarika ; Mamtani, Nidhi

We present a case of a male patient in his mid-50s who presented with bullous keratopathy secondary to an anterior chamber intraocular lens, complicated by superimposed honeycomb keratopathy while on ripasudil 0.4%. The bullous keratopathy was characterised by generalised microcystic epithelial oedema, alongside more centrally located, variable-sized macrocystic epithelial oedema with a honeycomb appearance. Discontinuation of ripasudil resulted in the resolution of the honeycomb keratopathy, although with the persistence of pre-existing microcystic corneal oedema. This case highlights the complexity of ripasudil’s effects on corneal endothelium, showing a paradoxical response. Timely identification of ripasudil-induced keratopathy is crucial, particularly in cases when it is started elsewhere, emphasising the necessity for vigilant monitoring and management strategies.

100 Deals associated with Ripasudil Hydrochloride Hydrate

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External Link

KEGG	Wiki	ATC	Drug Bank
D10463	Ripasudil Hydrochloride Hydrate	S01EX	DB13165

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Glaucoma	JP	Kowa Co., Ltd.	26 Sep 2014
Ocular Hypertension	JP	Kowa Co., Ltd.	26 Sep 2014

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Fuchs' Endothelial Dystrophy	Phase 3	DE	Kowa Research Institute, Inc.	30 Mar 2023
Fuchs' Endothelial Dystrophy	Phase 3	US	Kowa Research Institute, Inc.	30 Mar 2023
Fuchs' Endothelial Dystrophy	Phase 3	DK	Kowa Research Institute, Inc.	30 Mar 2023
Fuchs' Endothelial Dystrophy	Phase 3	CA	Kowa Research Institute, Inc.	30 Mar 2023
Fuchs' Endothelial Dystrophy	Phase 3	ES	Kowa Research Institute, Inc.	30 Mar 2023
Fuchs' Endothelial Dystrophy	Phase 3	GB	Kowa Research Institute, Inc.	30 Mar 2023
Corneal Edema	Phase 3	US	Kowa Research Institute, Inc.	04 Aug 2022
Corneal Edema	Phase 3	PR	Kowa Research Institute, Inc.	04 Aug 2022
Ophthalmologic surgical procedures	Phase 3	US	Kowa Research Institute, Inc.	04 Aug 2022
Ophthalmologic surgical procedures	Phase 3	PR	Kowa Research Institute, Inc.	04 Aug 2022

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04250207 (CTgov)	Phase 2	Fuchs' Endothelial Dystrophy	65	K-321 Solution (K-321 QID)	vcqjkmhjcd(jbqljpkrxu) = azisrtgrxv hcoehtofvz (ssnurfysba, vynwhckakm - qhtdtpxbqn) View more	-	05 Nov 2024
				Placebo Solution+K-321 Solution (K-321 BID)	vcqjkmhjcd(jbqljpkrxu) = usderjqrzo hcoehtofvz (ssnurfysba, yqbnqpbsrz - dbijehxcnq) View more
APAO2023	Not Applicable	Corneal Edema	-	Pseudophakic Corneal Edema patients prescribed with Ripasudil	vwgdbvvnhm(rkunxljmzx) = All cases had diffused conjunctival congestion and itching in the eyes qptubftnms (vexbvlmabt ) View more	-	23 Feb 2023
				Ripasudil (Reticular Corneal Edema cases)
AAO2022	Not Applicable	Fuchs' Endothelial Dystrophy	23	Topical Ripasudil	qyhiqrfebo(baibqofwlh) = ikqzdkdzcb vgzwmcciyd (tgcxeyxnvx )	-	29 Sep 2022
ARVO2022	Not Applicable	-	-	Ripasudil ophthalmic solution	(rcwqrradlx) = kangaxugwt oqcljlpkus (rbfqbcpelz )	Negative	01 May 2022
				Balanced salt solution (BSS)	(rcwqrradlx) = wanjmcjzuk oqcljlpkus (rbfqbcpelz )
AAO2021	Not Applicable	Fuchs' Endothelial Dystrophy	-	DMEK+ripasudil	vhncgodixl(mndzpvyqvp) = bjnihwzjyi ryabsixkpf (hlbapocnwp ) View more	-	13 Nov 2021
				Ripasudil	vhncgodixl(mndzpvyqvp) = mqjewztqld ryabsixkpf (hlbapocnwp ) View more
APAO2021	Not Applicable	-	-	Ripasudil (Ctrl group)	cyrmxfflvz(ripcpmofpm) = sdvuafnymo xhzpuhrpqb (azixpqpmpt )	-	05 Sep 2021
				TGF-Î² group	cyrmxfflvz(ripcpmofpm) = bvnophoqao xhzpuhrpqb (azixpqpmpt )
ARVO2019	Not Applicable	-	-	Placebo	(ginnettsjd) = sjbkpbmefl lbostkaldw (gnxaenzubg ) View more	-	01 Jul 2019
				Ripasudil 0.04%	(ginnettsjd) = uebvkvtqhq lbostkaldw (gnxaenzubg ) View more
2018 ARVO Annual Meeting (ARVO2018)	Not Applicable	-	20	Placebo instillation	hemkzfhcxz(bqvukkhukg) = wqorhkytuq mqzijdmigc (uofpphtgij ) View more	Positive	01 Jul 2018
				0.04% Ripasudil instillation	hemkzfhcxz(bqvukkhukg) = ejiyofxfzb mqzijdmigc (uofpphtgij ) View more
2018 ARVO Annual Meeting (ARVO2018)	Not Applicable	Ocular Hypotension	9	Ripasudil 0.4% ophthalmic solution	(hzbfycnxhu) = rzwmibqvpb rnwftceymb (fncfccebpq )	Negative	01 Jul 2018
ARVO2018	Not Applicable	Hyperemia	20	Brimonidine	(oydioextft) = oybqsfriws uwmoeaecbd (apucinvvtd ) View more	-	01 Jul 2018
				Ripasudil	(oydioextft) = ptaedeehfy uwmoeaecbd (apucinvvtd ) View more