Target Information | Therapeutic Target Database (2024)

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Target General Information

Drugs and Modes of Action

Cell-based Target Expression Variations

Chemical Structure based Activity Landscape of Target

Drug Property Profile of Target

Co-Targets

References

Target General Information		Top
Target ID	T84726
Target Name	Rho-associated protein kinase (ROCK)
Synonyms	Rho-associated, coiled-coil-containing protein kinase; Rho associated protein kinase Click to Show/Hide
Gene Name	NO-GeName
Target Type	Successful target	[1]
Disease	[+] 2 Target-related Diseases	+
1	Glaucoma [ICD-11: 9C61]
2	Myocardial infarction [ICD-11: BA41-BA43]
UniProt ID	NOUNIPROTAC

Drugs and Modes of Action						Top
Approved Drug(s)	[+] 2 Approved Drugs					+
1	Netarsudil	Drug Info	Approved	Open-angle glaucoma		[2]
2	Ximelegatran	Drug Info	Approved	Myocardial infarction		[3]
Clinical Trial Drug(s)	[+] 7 Clinical Trial Drugs					+
1	Roclatan	Drug Info	Phase 3	Glaucoma/ocular hypertension		[4]
2	AMA-76	Drug Info	Phase 2	Glaucoma/ocular hypertension		[5]
3	AR-12286	Drug Info	Phase 2	Glaucoma/ocular hypertension		[6]
4	Cethrin	Drug Info	Phase 1/2	Spinal cord injury		[7]
5	Y-39983	Drug Info	Phase 1/2	Glaucoma/ocular hypertension		[8]
6	AT13148	Drug Info	Phase 1	Solid tumour/cancer		[9]
7	STM 434	Drug Info	Phase 1	Ovarian cancer		[10]
Mode of Action	[+] 2 Modes of Action					+
Modulator	[+] 8 Modulator drugs					+
1	Netarsudil				Drug Info	[11]
2	Ximelegatran				Drug Info	[1], [12]
3	Roclatan				Drug Info	[13]
4	AMA-76				Drug Info	[14]
5	AR-12286				Drug Info	[15]
6	Cethrin				Drug Info	[16]
7	Y-39983				Drug Info	[17]
8	AT13148				Drug Info	[18]
Inhibitor	[+] 9 Inhibitor drugs					+
1	STM 434				Drug Info	[19]
2	Hexahydro azepinone derivative 1				Drug Info	[19]
3	Isoquinoline derivative 4				Drug Info	[19]
4	Isoquinoline derivative 5				Drug Info	[19]
5	Isoquinoline sulfonamide derivative 1				Drug Info	[19]
6	Isoquinoline sulfonamide derivative 2				Drug Info	[19]
7	Isoquinoline sulfonyl derivative 1				Drug Info	[19]
8	Isoquinoline sulfonyl derivative 2				Drug Info	[19]
9	Isoquinoline sulfonyl derivative 3				Drug Info	[19]

Chemical Structure based Activity Landscape of Target	Top

Drug Property Profile of Target		Top

(1) Molecular Weight (mw) based Drug Clustering	(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering	(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering	(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski'sruleoffive; "D123AB" colored in GREEN denotes the noviolation ofany cutoff in lipinski'sruleoffive; "D123AB" colored in PURPLE refers to theviolation ofonly one cutoff in lipinski'sruleoffive; "D123AB" colored in BLACK represents theviolation ofmore than one cutoffs in lipinski'sruleoffive

Co-Targets						Top
Co-Targets	Co-Targets Info

References		Top
REF 1	Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases. Mol Pharmacol. 2000 May;57(5):976-83.
REF 2	2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
REF 3	Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90.
REF 4	ClinicalTrials.gov (NCT02558400) Double-masked Study of PG324 Ophthalmic Solution in Patients With Glaucoma or Ocular Hypertension.
REF 5	ClinicalTrials.gov (NCT02136940) Multiple Dose-parallel-group Study of AMA0076 in Patients With Primary Open-Angle Glaucoma or Ocular Hypertension. U.S. National Institutes of Health.
REF 6	ClinicalTrials.gov (NCT01699464) A Study Assessing the Safety and Ocular Hypotensive Efficacy of AR-12286 in Patients With Elevated Intraocular Pressure for 3 Months. U.S. National Institutes of Health.
REF 7	Emerging drugs for spinal cord injury. Expert Opin Emerg Drugs. 2008 Mar;13(1):63-80.
REF 8	ClinicalTrials.gov (NCT00846989) Efficacy, Tolerability and Safety of RKI983 (0.05% & 0.10%) vs Xalatan in Patients With POAG or Ocular Hypertension. U.S. National Institutes of Health.
REF 9	ClinicalTrials.gov (NCT01585701) Phase I Study of AT13148, a Novel AGC Kinase Inhibitor. U.S. National Institutes of Health.
REF 10	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 11	Effect of 0.04% AR-13324, a ROCK, and norepinephrine transporter inhibitor, on aqueous humor dynamics in normotensive monkey eyes. J Glaucoma. 2015 Jan;24(1):51-4.
REF 12	Molecular characterization of the effects of Y-27632. Cell Motil Cytoskeleton. 2007 Feb;64(2):97-109.
REF 13	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
REF 14	AMA0076, a novel, locally acting Rho kinase inhibitor, potently lowers intraocular pressure in New Zealand white rabbits with minimal hyperemia. Invest Ophthalmol Vis Sci. 2014 Feb 18;55(2):1006-16.
REF 15	Ocular hypotensive effect of the Rho kinase inhibitor AR-12286 in patients with glaucoma and ocular hypertension. Am J Ophthalmol. 2011 Nov;152(5):834-41.e1.
REF 16	A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury. J Neurotrauma. 2011 May;28(5):787-96.
REF 17	Effects of Y-39983, a selective Rho-associated protein kinase inhibitor, on blood flow in optic nerve head in rabbits and axonal regeneration of retinal ganglion cells in rats.Curr Eye Res. 2011 Oct;36(10):964-70.
REF 18	Company report (Astex)
REF 19	Rho kinase inhibitors: a patent review (2014 - 2016).Expert Opin Ther Pat. 2017 Apr;27(4):507-515.

The residues interacting with the ligand at a distance of less than 5Å were defined as the drug binding pocket and labelled in ORANGE (Nat Commun. 14: 2175, 2023).

(1)The residues interacting with the ligand at a distance of less than 5Å were defined as the drug binding pocket and provided below (Nat Commun. 14: 2175, 2023).

(2)H-bonding was determined by a distance of less than 3.5 Å and the distances within 3.5 Å were underlined (J Am Chem Soc. 142: 14150-14157, 2020).

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