Delving into the Latest Updates on Verosudil with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Verosudil (USAN/INN), Verosudil Hydrochloride, AR-12286

+ [1]

Target

ROCK

Mechanism

ROCK inhibitors(Rho-associated kinases inhibitors)

Therapeutic Areas

Eye Diseases

Active Indication-

Inactive Indication

GlaucomaGlaucoma, Open-AngleOcular Hypertension+ [1]

Originator Organization

Aerie Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

Aerie Pharmaceuticals, Inc.

Drug Highest PhasePendingPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC17H17N3O2S

InChIKeyVDYRZXYYQMMFJW-UHFFFAOYSA-N

CAS Registry1414854-42-4

A. To evaluate the ocular hypotensive efficacy of the rho-kinase Inhibitor (AR-12286 0.5% and 0.7%) ophthalmic solutions in glaucoma patients with failed prior glaucoma filtering surgery and uncontrolled IOP who are facing further surgical intervention. Patients will be treated for 6 months in this initial trial.
B. To evaluate the efficacy of AR-12286 in enabling treated patients to delay or avoid the necessity of further surgical intervention.

Start Date01 Jun 2014

Sponsor / Collaborator

New York Glaucoma Research Institute

NCT02152774

/ Unknown statusPhase 2IIT

A Prospective Study to Assess the Hypotensive Efficacy of Rho-Kinase Inhibitor AR-12286 Ophthalmic Solution 0.5% and 0.7% in Patients With Chronic Angle-closure Glaucoma

To evaluate the ocular hypotensive efficacy of Rho kinase Inhibitor (AR-12286 0.5% and 0.7%) ophthalmic solutions in patients diagnosed with chronic angle-closure glaucoma treated for 6 months.
Secondary Outcome
Secondary objectives are:
To evaluate the early effect of Rho kinase Inhibitor (AR-12286) in reducing intraocular pressure (IOP).
To evaluate the long term effect of the drug on IOP.
To determine if AR-12286 can be used as directed therapy for CACG, reducing or eliminating the structural blockage of the trabecular meshwork that leads to development of elevated IOP.

Start Date01 May 2014

Sponsor / Collaborator

New York Glaucoma Research Institute

100 Clinical Results associated with Verosudil

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100 Translational Medicine associated with Verosudil

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100 Patents (Medical) associated with Verosudil

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11

Literatures (Medical) associated with Verosudil

13 Apr 2023·Journal of medicinal chemistryQ1 · MEDICINE

Application and Study of ROCK Inhibitors in Pulmonary Fibrosis: Recent Developments and Future Perspectives.

Q1 · MEDICINE

Review

Author: Su, Xingping ; Ye, Tinghong ; Xue, Taixiong ; Xie, Yuting ; Yue, Lin ; Shi, Yaojie ; Liu, Hongyao ; Gan, Cailing

Rho-associated coiled-coil-containing kinases (ROCKs), serine/threonine protein kinases, were initially identified as downstream targets of the small GTP-binding protein Rho. Pulmonary fibrosis (PF) is a lethal disease with limited therapeutic options and a particularly poor prognosis. Interestingly, ROCK activation has been demonstrated in PF patients and in animal PF models, making it a promising target for PF treatment. Many ROCK inhibitors have been discovered, and four of these have been approved for clinical use; however, no ROCK inhibitors are approved for the treatment of PF patients. In this article, we describe ROCK signaling pathways and the structure-activity relationship, potency, selectivity, binding modes, pharmacokinetics (PKs), biological functions, and recently reported inhibitors of ROCKs in the context of PF. We will also focus our attention on the challenges to be addressed when targeting ROCKs and discuss the strategy of ROCK inhibitor use in the treatment of PF.

03 Feb 2023·Investigative ophthalmology & visual science

Rho Kinase Inhibitor AR-12286 Reverses Steroid-Induced Changes in Intraocular Pressure, Effective Filtration Areas, and Morphology in Mouse Eyes

Article

Author: Kopczynski, Casey ; Gong, Haiyan ; Ren, Ruiyi ; Humphrey, Anne A.

Purpose:

We investigated mechanisms of reduction of intraocular pressure (IOP) by Rho kinase inhibitor AR-12286 in steroid-induced ocular hypertension (SIOH).

Methods:

C57BL/6 mice (N = 56) were randomly divided into Saline, dexamethasone (DEX), DEX + AR-12286, and DEX-discontinuation (DEX-DC) groups. IOP was measured weekly during the first four weeks in all groups. Beginning at week 5, the DEX-DC group was followed without treatment until IOP returned to normal, and the other groups were treated as assigned with IOP measured every other day for another week. Fluorescent tracer was injected into the anterior chamber to visualize the outflow pattern in the trabecular meshwork (TM) and TM effective filtration area (EFA) was determined. Radial sections from both high- and low-tracer regions were processed for electron microscopy.

Results:

AR-12286 reduced IOP in SIOH mouse eyes in one day (P < 0.01). At the end of week 5, mean IOP in the DEX + AR-12286 group was ∼4 mm Hg lower than DEX group (P < 0.001) and ∼2 mm Hg lower than DEX-DC group (P < 0.05). After one-week AR-12286 treatment (P < 0.05) or five-week DC of DEX (P < 0.01), DEX-induced reduction of EFA was rescued and DEX-induced morphological changes in the TM were partially reversed.

Conclusions:

AR-12286 reversed steroid-induced morphological changes in the TM and reduced EFA, which correlated with reduced IOP in SIOH eyes. AR-12286 reduced IOP elevation in SIOH eyes more effectively than discontinuing DEX treatment even when accompanied by continuous DEX treatment. Therefore Rho kinase inhibitors may lower SIOH in patients who rely on steroid treatment.

01 Jan 2021·Materials today. Proceedings

In-Silico analysis to identify the potent inhibitor of Rho GTPase activating protein for the usage of the Glaucoma

Author: R. Thiruchelvi ; C. Shivanika

Considered as the one of the leading irreversible loss of vision causing optic neuropathy, Glaucoma is estimated to hit more than 80 million by the end of 2020 via population survey.Increased intraocular pressure is taken as one of the risk factors among others behind the root of causing the disease.The imbalance in the secretion and the excretion of the aqueous humor inside and out of the ocular results in the IOP to deviate from the normal value of 22 mm of Hg.The Rho GAP pathway playing a crucial role in the modulation of the contractile and relaxation property of the actin smooth muscle, has shown in neg. regulating the protein kinase and subsequently increased IOP.In-vitro and Ex-vitro inhibition of the Rho GTPase protein through inhibitors have resulted in the relaxation of the actin and hence the IOP.The aim of the study is to use the in-silico technique such as, Autodock4, to explore the ligand interaction and its ability to inhibit the activity of RhoGTPase.The mols. AZA1 and Azaindole, with the least binding energies, have proven to be a potent inhibitor of the protein, hence as a lead towards the treatment of the glaucoma by decreasing the IOP to an extent.

1

News (Medical) associated with Verosudil

10 Jan 2025

·www.prnewswire.com

Woolsey Pharmaceuticals Secures Additional Key U.S. Patent Claims for BRAVYL® (oral fasudil) in Treating ALS, Including Reducing Neurofilament Light (NfL)

NEW YORK, Jan. 10, 2025 /PRNewswire/ -- Woolsey Pharmaceuticals, whose mission is to usher in a new era of neurodegenerative disease treatment, today announced that the U.S. Patent and Trademark Office (USPTO) has granted additional claims for the use of BRAVYL in treating ALS. This latest patent allowance covers treatment of possible, probable laboratory-supported, probable, or definite ALS, as defined by El Escorial Revised ALS diagnostic criteria, using fasudil or its active metabolite. Further claims are directed to reducing neurofilament light (NfL). In Woolsey's REAL study of BRAVYL at 180mg/day, NfL was reduced by 15% from baseline to six months (p=0.0006). Data from the 300 mg/day REAL cohort is expected in June 2025. Once issued, this patent will add to Woolsey's existing portfolio, which includes: US Patent No. 11,779,588, covering the treatment of sporadic ALS with fasudil or its active metabolite; US Patent No.12,128,053, covering treating (sporadic or familial) ALS using Woolsey's proprietary dysphagia-friendly formulation; and US Patent Nos. 11,944,633 and 12,115,167, covering a range of dysphagia-friendly formulations of fasudil. BRAVYL (oral fasudil), a Rho-kinase inhibitor, is an investigational drug believed to work by targeting cellular mechanisms that contribute to neuronal damage and dysfunction. Preclinical and clinical studies suggest that BRAVYL may reduce motor-neuron death, making it a promising candidate for ALS. "These robust and strategically vital patent claims are part of a 36-patent-family portfolio we have developed for fasudil, a number of which have already issued," said Sven Jacobson, Chief Executive Officer of Woolsey Pharmaceuticals. "These newest patent claims further strengthen our proprietary position around the use of BRAVYL to treat ALS, and complement BRAVYL's ALS Orphan Drug Designations in both the U.S. and Europe." About ALS ALS is a fatal neurodegenerative disease characterized by inevitable, and often rapid, decline in patients as the disorder advances. Mean survival time is only two to five years. Accordingly, the ability to impede any worsening represents a meaningful advancement in efforts to enhance the prognosis and quality of life of individuals impacted by the devastating condition. About Woolsey Pharmaceuticals: New York-based Woolsey Pharmaceuticals, Inc. is a privately held, clinical-stage pharmaceutical company focused on developing and bringing lifesaving treatments to people affected by ALS and other neurodegenerative diseases. SOURCE Woolsey Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Orphan Drug

100 Deals associated with Verosudil

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External Link

KEGG	Wiki	ATC	Drug Bank
D10737	Verosudil	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Ocular Hypertension	Phase 3	-	Aerie Pharmaceuticals, Inc.	-
Glaucoma, Open-Angle	Phase 2	US	Aerie Pharmaceuticals, Inc.	01 May 2011
Glaucoma	Phase 2	US	Aerie Pharmaceuticals, Inc.	01 Feb 2010
Ocular Hypotension	Phase 2	US	Aerie Pharmaceuticals, Inc.	01 May 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01936389 (Pubmed \| J Glaucoma) Manual	Phase 2	Ocular Hypertension \| Exfoliation Syndrome \| Glaucoma	10	AR-12286	grwplummzy(cwwdiildmp) = eudwekncou lknodskcud (glpbilskue ) View more	Positive	01 Sep 2016
NCT01936389 (ROCK, CTgov)	Phase 2	Glaucoma, Open-Angle \| Exfoliation Syndrome	10	AR-12286 (0.5%)	zcjeheiilx(sztvlmrghu) = psnbtlpfqu bctwahijgr (bghjhdfeog, rsgruxkwmt - qnmuzhalhq) View more	-	24 Apr 2015
				AR-12286 (0.7%)	zcjeheiilx(sztvlmrghu) = rpsrjttirz bctwahijgr (bghjhdfeog, avvqftvtuf - jcivorgjmt) View more
ARVO2013	Not Applicable	Ocular Hypotension	93	AR-12286 0.25%	eutrphshbg(hujdzapmkx) = The most frequently reported events were mild to moderate conjunctival hyperemia, 32% (10/31), 59% (17/29) and 42% (14/33) in the PG286-0.25%, PG286-0.5% and travoprost groups, respectively. The incidence of conjunctival hyperemia of grade 2 or greater at Day 7 was 0%, 12% and 12%, respectively. cujyizkuui (zbnfuztttc )	Positive	01 Jun 2013
				AR-12286 0.5%
NCT00902200 (Pubmed \| Am J Ophthalmol)	Phase 2	Ocular Hypertension \| Glaucoma	89	0.05% AR-12286 Ophthalmic Solution	abnxlvltxl(oodvtbozem) = sridqzqpja qnkylvrnvj (nzufzboxwk ) View more	Positive	01 Nov 2011
				0.1% AR-12286 Ophthalmic Solution	abnxlvltxl(oodvtbozem) = afmmfnhjsi qnkylvrnvj (nzufzboxwk ) View more
PO105 (AAO2011)	Not Applicable	-	18	0.5% AR-12286 Ophthalmic Solution	ypivwmvkhd(ptyxankbbb) = trace to moderate transient conjunctival hyperemia krxrvmvhjx (sthnihmrqg )	Positive	23 Oct 2011
NCT01250197 (ARVO2011)	Phase 1	-	18	0.5% AR-12286 Ophthalmic Solution	qyojnuphya(mokzukmjke) = trace to moderate conjunctival hyperemia that gradually returned to baseline by 8 hrs after dosing vsrvgikztl (wmzyvaujea )	Positive	01 Apr 2011