Delving into the Latest Updates on Dorzolamide Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

(4S,6S)-4-ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7lambda*6*-thieno[2,3-b]thiopyran-2-sulfonic acid amide, (4S,trans)-4-(ethylamino)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide, 4-Ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7lambda*6*-thieno[2,3-b]thiopyran-2-sulfonic acid amide

+ [8]

Target

CAs

Mechanism

CAs inhibitors(Carbonic anhydrases inhibitors)

Therapeutic Areas

Eye Diseases

Active Indication

GlaucomaOcular Hypertension

Inactive Indication

Glaucoma, Open-Angle

Originator Organization

Merck & Co., Inc.

Active Organization

Santen Pharmaceutical Co., Ltd.

Inactive Organization

Merck Sharp & Dohme Corp.

Drug Highest PhaseApproved

First Approval Date

US (09 Dec 1994),

Glaucoma, Open-AngleOcular Hypertension

Regulation-

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Structure

Molecular FormulaC10H17ClN2O4S3

InChIKeyOSRUSFPMRGDLAG-QMGYSKNISA-N

CAS Registry130693-82-2

This study is a double-blind randomized clinical trial in Diabetic patients (type 2) over 18 years of age who have diabetic macular edema with involvement of the central 1 millimeter (central macular thickness is more than 300 μm) and BCVA 20/30 or less who visit the retina clinic of Labbafinejad Hospital Are studied. (In patients with bilateral macular edema, only one eye is included in the study.) Complete ocular examinations (including best corrected visual acuity - anterior segment - intraocular pressure - dilated pupil funduscopy with severity of diabetic retinopathy), optical coherence tomography (OCT), EDI-OCT( Enhanced Depth Imaging Optical Coherence Tomography ) - as well as Optical coherence tomography angiography (OCTA ) are performed for all patients at baseline. Blood tests are also taken from patients for fasting blood sugar and HbA1C. Patients are then randomly divided into two groups. The first group is treated with injections of 1.25 mg of intravitreal bevacizumab monthly for 3 months (months 0, 1 and 2) with topical drops of Timolol twice a day and Dorzolamide twice a day. For the second group (control group), 3 injections of 1.25 mg of intravitreal bevacizumab monthly with artificial tears (twice a day as a placebo) are prescribed. Patients in both groups are visited 1 month after the third basic intravitreal bevacizumab (IVB) injection and complete ophthalmology examinations are performed and central thickness of macula is recorded based on the patient's OCT as well as the need for IVB re-injection. EDI (Enhanced Depth Imaging)-OCT and OCTA are performed again for all patients.

Start Date06 Oct 2021

Sponsor / Collaborator

Shahid Beheshti University of Medical Sciences

IRCT20210519051344N1 / CompletedPhase 2IIT

Studying the effect of combination topical therapy using three medications (Dorzolamide drops, Ketorolac drops, Prednisolone drops) in treatment of Ivrin Gass syndrome (CME) post cataract surgery

Start Date22 Jun 2021

Sponsor / Collaborator

Tabriz University of Medical Sciences

100 Clinical Results associated with Dorzolamide Hydrochloride

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100 Translational Medicine associated with Dorzolamide Hydrochloride

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100 Patents (Medical) associated with Dorzolamide Hydrochloride

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1,155

Literatures (Medical) associated with Dorzolamide Hydrochloride

01 Jan 2025·EUROPEAN JOURNAL OF PHARMACOLOGY

Dorzolamide intermediates with potential anti-inflammatory activity

Article

Author: Nair, Krishnaprasad ; Hassan, Md Imtaiyaz ; Varma, Vivek P ; Obukhov, Alexander G ; White, Fletcher A ; Darwhekar, Gajanan N ; Sharma, Rahul ; Baig, Mirza S ; Siddiqi, Faaiza ; Mohammad, Taj ; Atre, Rajat ; Faisal, Syed M ; Majmudar, Chinmay Y

Dorzolamide (DZD), a Carbonic anhydrase (CA) inhibitor clinically used to lower intraocular pressure, exhibits anti-inflammatory effects owing to the drug's ability to inhibit the TIR domain-containing adaptor protein (TIRAP)-mediated signalling in macrophages. Here, we investigated whether DZD intermediates also demonstrate any anti-inflammatory property like DZD but with a reduced inhibition of CA. We found that several intermediates of DZD show increased binding to TIRAP at the common interface of kinases, such as Protein kinase C-delta (PKCδ) and Bruton's tyrosine kinase (BTK). Such binding results in a decreased activity of TIRAP, p38 Mitogen-activating protein kinases (MAPK), and p65, which are essential for major inflammatory signaling pathways. Remarkably, the DZD intermediates were more effective than DZD in decreasing the mRNA expression levels of pro-inflammatory cytokines in Lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The DZD intermediates also exhibit a reduced binding energy to CA II and CA IV, highlighting their improved specificity as anti-inflammatory compounds with decreased unwanted biological effects. Furthermore, we validated the anti-inflammatory effect of the most efficient DZD intermediate, DRZ V, in a model of mouse sepsis. DRZ V-treated septic mice exhibited improved survival compared to DZD-treated septic mice. Our data indicate that the tested DZD intermediates are more effectual in dampening TIRAP-mediated inflammatory signaling as compared to DZD. Thus, DZD intermediates may be a promising option for developing novel anti-inflammatory therapeutics.

01 Jan 2025·AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY

Effects of patient pleural effusion fluids on the BBSome components expression of human benign mesothelial cells

Article

Author: Rouka, Erasmia ; Papazoglou, Eleftherios D. ; Pitaraki, Eleanna ; Sarrigeorgiou, Ioannis ; Hatzoglou, Chrissi ; Giannou, Anastasios D. ; Lymberi, Peggy ; Malami, Zoi ; Jagirdar, Rajesh M. ; Zarogiannis, Sotirios G. ; Sinis, Sotiris I. ; Kotsiou, Ourania S. ; Marnas, Periklis ; Gourgoulianis, Konstantinos I.

Studying mesothelial PC in pleural physiology and pathophysiology is at an early stage. Previously, we have highlighted the role of the PC in mesothelial cell phenotypes as well as the role of BBSome components in the context of benign and malignant mesothelial cell physiology. Here we extended our contributions by providing evidence on the BBSome changes induced in benign mesothelial cells by their exposure to different etiology PFs.

01 Dec 2024·DRUG DEVELOPMENT RESEARCH

Design and Discovery of New Dual Carbonic Anhydrase IX and VEGFR‐2 Inhibitors Based on the Benzenesulfonamide‐Bearing 4‐Thiazolidinones/2,4‐Thiazolidinediones Scaffold

Article

Author: Arafa, Reem K. ; Balkan, Ayla ; Unsal Tan, Oya ; Zengin, Merve ; Sabuncuoglu, Suna

ABSTRACT:

Dual‐targeting drug design has become a popular approach in investigating and developing potent anticancer agents. In this regard, carbonic anhydrase (CAIX) and vascular endothelial growth factor receptor (VEGFR‐2) are emerging as highly effective targets in the battle against cancer. In the present study, two series of 4‐thiazolidinones/2,4‐thiazolidinediones carrying 2‐methylbenzenesulfonamide derivatives were designed and synthesized as potential dual CAIX/VEGFR‐2 inhibitors. All the target compounds were evaluated against CAIX enzyme compared to dorzolamide and acetazolamide, subsequently the most potent CAIX inhibitors (3a, 3b, 3o, 6d, 6g, and 6i) were selected to evaluate their inhibitory activity against VEGFR‐2 using sorafenib as a reference drug. These compounds were also evaluated against MCF‐7 breast cancer cells and the murine fibroblast 3T3 cell line. According to the results, 3b (CAIX IC50 = 0.035 µM, VEGFR‐2 IC50 = 0.093 µM) and 6i (CAIX IC50 = 0.041 µM, VEGFR‐2 IC50 = 0.048 µM) emerged the most potent compounds against CAIX and VEGFR‐2. Furthermore, docking studies of selected compounds were performed with the CAIX and the tyrosine kinase domain of VEGFR‐2 to comprehend the ligand‐binding interactions. Physicochemical predictions were examined using in silico techniques. In conclusion, these scaffolds present promising leads and furnish promising chemical backbones for the design of potent dual CAIX and VEGFR‐2 inhibitors.b

100 Deals associated with Dorzolamide Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D00653	Dorzolamide Hydrochloride	S01EC03	DB00869

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Glaucoma	JP	Santen Pharmaceutical Co., Ltd.	12 Mar 1999
Glaucoma, Open-Angle	US	Merck Sharp & Dohme Corp.	09 Dec 1994
Ocular Hypertension	US	Merck Sharp & Dohme Corp.	09 Dec 1994

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


DMAC (EURETINA2024) Manual	Not Applicable	Dystrophy, Macular	32	Dorzolamidezolamide 2%	nvattbjnqp(dovocyypvw) = rlsacekovn tnxrjcglsr (mneypeilty )	Negative	19 Sep 2024
				Saline	nvattbjnqp(dovocyypvw) = pmmewbnfmb tnxrjcglsr (mneypeilty )
NCT00716586 (CTgov)	Phase 4	Macular Edema	44	2% dorzolamide	lnltwdusnh(yzzquattng) = hkbekmsdhx tnbdskwkix (vdmxhumfgz, tbmgdycjmd - zmcdvcabtg) View more	-	15 Oct 2021
ARVO2021	Not Applicable	Retinitis Pigmentosa	40	Topical 1.0% Dorzolamide	kjildbchjn(eemxyezztz) = ysbagriqif mfpxefedrq (zwrpydtbkd )	-	01 Jun 2021
2018 ARVO Annual Meeting (ARVO2018)	Not Applicable	Bloodshot eye	30	Dorzolamide 2%	tpfvzmbmnt(ttgrxocply) = haaahkehta ldtdmmxhzp (sbiawewslu )	-	01 Jul 2018
				Placebo	tpfvzmbmnt(ttgrxocply) = xeaovtyjaj ldtdmmxhzp (sbiawewslu )
ARVO2014	Not Applicable	Scleral Diseases	-	dorzolamide (Rabbit Sclera)	jgipcmeyno(kezbkkiveq) = viqqujafhi rhfmkewvov (jgmomeggdh ) View more	-	01 Apr 2014
AAO2012	Not Applicable	Ocular Hypertension	-	Dorzolamide/Timolol	mxexrzipbs(ibfdthrobf) = kdhiruefzp avvxdeljrk (vinxazfyco, 7.3)	Negative	12 Nov 2012
				Brimonidine/Timolol	mxexrzipbs(ibfdthrobf) = tznoepoyfw avvxdeljrk (vinxazfyco, 5.1)
ARVO2010	Not Applicable	Macular Edema	20	Topical 2% Dorzolamide	erhwtrloxo(dqrcvthoha) = qldinciszp iytidbktfw (eugteymomx )	-	01 Apr 2010
				Topical Dorzolamide (Control Group)	erhwtrloxo(dqrcvthoha) = etimdhttrt iytidbktfw (eugteymomx )
ARVO2010	Not Applicable	-	-	Latanoprost monotherapy	hgqgtozfff(ecuuaqahak) = baxzttuxfn xhqdooagdo (vherxipipa ) View more	Positive	01 Apr 2010
				Latanoprost + Dorzolamide	hgqgtozfff(ecuuaqahak) = cpkuafdlky xhqdooagdo (vherxipipa ) View more
PO113 (AAO2008)	Not Applicable	Ocular Hypotension	104	Krytantek Ofteno (KO)	ormenquwbl(lmthexbkhc) = edjusxzivd owdnuflnuo (tkotskgieo )	Positive	09 Nov 2008
				Cosopt (COS)	ormenquwbl(lmthexbkhc) = pkfynadiip owdnuflnuo (tkotskgieo )