ROCK inhibitor
### ROCK Inhibitors: Overview and Applications
#### 1. What are ROCK Inhibitors? ROCK inhibitors are pharmacological agents that block the activity of Rho-associated protein kinase (ROCK), a key enzyme in the RhoA/ROCK signaling pathway. These inhibitors reduce actin-myosin contractility, influencing various cellular processes like migration, proliferation, and adhesion.
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#### 2. Mechanism of Action ROCK inhibitors prevent the phosphorylation of: - Myosin Light Chain (MLC): Reduces actin-myosin contraction. - LIM Kinase (LIMK): Affects actin stability. - Adhesion Proteins: Modulate cellular stiffness and motility.
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#### 3. Common ROCK Inhibitors
Inhibitor | Clinical Use | Key Features |
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Fasudil | Cerebral vasospasm, hypertension | Approved in Japan; improves vasodilation. |
Ripasudil | Glaucoma | Lowers intraocular pressure. |
Y-27632 | Research (fibrosis, neuroprotection) | Widely used in preclinical studies. |
AT13148 | Cancer (experimental) | Targets multiple kinases, including ROCK. |
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#### 4. Clinical Applications - Cardiovascular Diseases:
- Hypertension: ROCK inhibitors reduce vascular resistance and blood pressure.
- Pulmonary Hypertension: Improve arterial function by relaxing smooth muscle.
- Neurological Disorders:
- Stroke: Enhance neuroprotection and axonal regeneration.
- Spinal Cord Injury: Promote axon growth and functional recovery.see ROCK inhibitor for spinal cord injury
- Neurodegenerative Diseases: Potential benefits in Parkinson’s and Alzheimer’s.
- Ophthalmology:
- Glaucoma: Ripasudil improves aqueous humor outflow, reducing intraocular pressure.
- Oncology:
- Cancer Metastasis: Reduce tumor cell migration and invasion.
- Fibrosis:
- Lung, Liver, and Kidney Fibrosis: Decrease fibroblast activation and extracellular matrix deposition.
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#### 5. Emerging Research - Development of selective ROCK2 inhibitors to minimize side effects. - Combination therapies with ROCK inhibitors for enhanced efficacy in oncology and neurological diseases.