Explore a selection of our essential drug information below, or:
Identification
- Summary
Ripasudil is a rho kinase inhibitor indicated to treat ocular hypertension and open-angle glaucoma.
- Generic Name
- Ripasudil
- DrugBank Accession Number
- DB13165
- Background
Ripasudil, as hydrochloride hydrate (K-115), is a specifc Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor used for the treatment of glaucoma and ocular hypertension. It was first approved for treatment in Japan in September 2014. This medication is available in the form of a 0.4% eye drop solution under the brand name Glanatec. Ripasudil is a well tolerated medication that is used when other drugs have been proven to be non-effective or cannot be administered.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Ripasudil (DB13165)
- Weight
- Average: 323.39
Monoisotopic: 323.110376169 - Chemical Formula
- C15H18FN3O2S
- Synonyms
- Ripasudil
Pharmacology
- Indication
Ripasudil has been proven to be effective in the twice daily treatment of glaucoma and ocular hypertension. It is currently in studies to be approved for both diabetic retinopathy and diabetic macular oedema.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Ocular hypertension •••••••••••• •••••••••• •• •• •••••••••• •• ••••• ••••••••• •••••••• • ••••• Adjunct therapy in treatment of Ocular hypertension •••••••••••• •••••••••••• •••••••• •• ••••••• ••••••••••••• ••• ••••••••••••• ••••••••• •••••••• • ••••• Treatment of Open-angle glaucoma (oag) •••••••••••• •••••••••• •• •• •••••••••• •• ••••• ••••••••• •••••••• • ••••• Adjunct therapy in treatment of Open-angle glaucoma (oag) •••••••••••• •••••••••••• •••••••• •• ••••••• ••••••••••••• ••• ••••••••••••• ••••••••• •••••••• • ••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Ripasudil has high intraocular permeability and works by decreasing intraocular pressure (IOP) in a dose-dependent manner and increasing flow facility. The maximum reduction of IOP occurs after 1 to 2 hours.
- Mechanism of action
Ripasudil is a highly selective and potent Rho-associated coiled/coil-containing kinase protein (ROCK) inhibitor. Rho-kinase (ROCK) is an effector protein of Rho which binds with Rho to form a Rho/Rho-kinase complex. This complex then regulates many physiological functions including smooth muscle contractions, chemotaxis, neural growth and gene expression. ROCK comes in 2 isoforms: ROCK-1 and ROCK-2 and these two isoforms are distributed widely in our tissues including ocular tissues such as the iris, retina, trabecular meshwork and ciliary muscles. Atypical regulation of ROCK levels is involved in the pathogenesis of diseases such as glaucoma, ocular hypertension, cataracts and other retinal disorders.
Ripasudil acts as very highly selective and potent inhibitor with an IC50 of Ripasudil with ROCK-1 of 0.051 umol/L and with ROCK-2 of 0.019 umol/L. ROCK inhibitors have efficacy in reducing IOP by acting on the trabecular meshwork in the eye directly to increase conventional outflow through the Schlemm’s canal. Ripasudil will inhibit ROCK and induce cytoskeletal changes including the retraction and rounding of cell bodies and cause disruption of actin bundles in this trabecular meshwork. This can reduce the compaction of trabecular meshwork tissue and eventually result in increased aqueous outflow in the eye and reduced resistance to fluid flow.
Thus, Ripasudil is effective by inducing cytoskeletal changes which are depending on ROCK inhibition. Ripasudil decreases IOP by increasing outflow facility along with modulating the behavior of trabecular meshwork cells and Schlemm’s canal endothelial (SCE) cell permeability along with a disruption of the tight junction.
When Ripasudil is used in combination with prostaglandin analogues it results in increased uveoscleral outflow and when used in combination with beta blockers it results in reduced aqueous production.
Target Actions Organism URho-associated protein kinase 1 inhibitorHumans URho-associated protein kinase 2 inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
The plasma protein binding rate of Ripasudil is 55.4-59.8%
- Metabolism
- Not Available
- Route of elimination
Riapsudil is cleared by the kidneys at a rate of 7.112L/h.
- Half-life
The half life of Ripasudil is 0.455 hrs.
- Clearance
Ripasudil has a renal clearance of 7.112 L/h.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The most frequent adverse effect of Ripasduil is mild to moderately severe conjunctival hyperemia which was found to cease spontaneously within hours. Mild conjunctival follicles were also reported which also were spontaneously resolved. Other adverse effects include ocular irritation, an abnormal sensation in the eye and conjunctival haemorrhage.
Ripasudil has not been found to have any effects to other receptors and enzymes including serine-threonine protein kinases.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Ripasudil hydrochloride dihydrate 016TTR32QF 887375-67-9 CMDJNMACGABCKQ-XVSRHIFFSA-N
Categories
- ATC Codes
- S01EX07 — Ripasudil
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as isoquinolines and derivatives. These are aromatic polycyclic compounds containing an isoquinoline moiety, which consists of a benzene ring fused to a pyridine ring and forming benzo[c]pyridine.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Isoquinolines and derivatives
- Sub Class
- Not Available
- Direct Parent
- Isoquinolines and derivatives
- Alternative Parents
- 1,4-diazepanes / Pyridines and derivatives / Organosulfonamides / Benzenoids / Aryl fluorides / Sulfonyls / Heteroaromatic compounds / Dialkylamines / Azacyclic compounds / Organofluorides show 2 more
- Substituents
- 1,4-diazepane / Amine / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Diazepane / Heteroaromatic compound / Hydrocarbon derivative show 15 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 11978226XX
- CAS number
- 223645-67-8
- InChI Key
- QSKQVZWVLOIIEV-NSHDSACASA-N
- InChI
- InChI=1S/C15H18FN3O2S/c1-11-8-17-6-3-7-19(11)22(20,21)14-5-2-4-12-9-18-10-13(16)15(12)14/h2,4-5,9-11,17H,3,6-8H2,1H3/t11-/m0/s1
- IUPAC Name
- 4-fluoro-5-{[(2S)-2-methyl-1,4-diazepan-1-yl]sulfonyl}isoquinoline
- SMILES
- C[C@H]1CNCCCN1S(=O)(=O)C1=C2C(F)=CN=CC2=CC=C1
References
- General References
- Kaneko Y, Ohta M, Inoue T, Mizuno K, Isobe T, Tanabe S, Tanihara H: Effects of K-115 (Ripasudil), a novel ROCK inhibitor, on trabecular meshwork and Schlemm's canal endothelial cells. Sci Rep. 2016 Jan 19;6:19640. doi: 10.1038/srep19640. [Article]
- Garnock-Jones KP: Ripasudil: first global approval. Drugs. 2014 Dec;74(18):2211-5. doi: 10.1007/s40265-014-0333-2. [Article]
- Tanihara H, Inoue T, Yamamoto T, Kuwayama Y, Abe H, Araie M: Phase 1 clinical trials of a selective Rho kinase inhibitor, K-115. JAMA Ophthalmol. 2013 Oct;131(10):1288-95. doi: 10.1001/jamaophthalmol.2013.323. [Article]
- NPRA Product Information: Glanatec (ripasudil hydrochloride) ophthalmic solution [Link]
- External Links
- PubChem Compound
- 9863672
- PubChem Substance
- 347829272
- ChemSpider
- 8039366
- BindingDB
- 50087135
- ChEBI
- 136046
- ChEMBL
- CHEMBL3426621
- ZINC
- ZINC000003940873
- Wikipedia
- Ripasudil
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data4 Recruiting Treatment Fuchs' Endothelial Dystrophy 1 somestatus stop reason just information to hide 3 Completed Treatment Corneal Edema After Cataract Surgery 1 somestatus stop reason just information to hide 3 Completed Treatment Ocular Hypertension / Ocular Hypertension, Primary Open-angle Glaucoma (POAG) 1 somestatus stop reason just information to hide 3 Recruiting Prevention Cataracts / Fuchs' Endothelial Dystrophy 1 somestatus stop reason just information to hide 3 Recruiting Treatment Fuchs 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution / drops Ophthalmic 0.4 % Solution / drops Ophthalmic 4 mg/1ml Solution Ophthalmic 0.4 g/100ml - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.3 mg/mL ALOGPS logP 0.72 ALOGPS logP 0.88 Chemaxon logS -3 ALOGPS pKa (Strongest Basic) 8.2 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 62.3 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 82.56 m3·mol-1 Chemaxon Polarizability 31.25 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-0009000000-12f6b5e264097601dc6d Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0009000000-14dc70730301e80be63b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-0109000000-a5cc0ac99ad4c38d32f9 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0319000000-57a097b86cd92c41c3fe Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0900000000-683941946cac31af6139 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-006t-3921000000-8167f57489c794cbb652 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 167.07668 predictedDeepCCS 1.0 (2019) [M+H]+ 169.43468 predictedDeepCCS 1.0 (2019) [M+Na]+ 175.99394 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Protein kinase which is a key regulator of the actin cytoskeleton and cell polarity (PubMed:10436159, PubMed:10652353, PubMed:11018042, PubMed:11283607, PubMed:17158456, PubMed:18573880, PubMed:19131646, PubMed:8617235, PubMed:9722579). Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, TPPP, PFN1 and PPP1R12A (PubMed:10436159, PubMed:10652353, PubMed:11018042, PubMed:11283607, PubMed:17158456, PubMed:18573880, PubMed:19131646, PubMed:23093407, PubMed:23355470, PubMed:8617235, PubMed:9722579). Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing (PubMed:18694941). Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress (PubMed:19036714). Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability (By similarity). Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation (PubMed:19181962). Required for centrosome positioning and centrosome-dependent exit from mitosis (By similarity). Plays a role in terminal erythroid differentiation (PubMed:21072057). Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1 (By similarity). Promotes keratinocyte terminal differentiation (PubMed:19997641). Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization (By similarity). May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles (By similarity)
- Specific Function
- Atp binding
- Gene Name
- ROCK1
- Uniprot ID
- Q13464
- Uniprot Name
- Rho-associated protein kinase 1
- Molecular Weight
- 158173.545 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation
- Specific Function
- Atp binding
- Gene Name
- ROCK2
- Uniprot ID
- O75116
- Uniprot Name
- Rho-associated protein kinase 2
- Molecular Weight
- 160898.555 Da
Drug created at January 20, 2017 21:20 / Updated at June 05, 2021 09:12