Target Information

Target General Information

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Target ID

T84726

Target Name

Rho-associated protein kinase (ROCK)

Synonyms

Rho-associated, coiled-coil-containing protein kinase; Rho associated protein kinase

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Gene Name

NO-GeName

Target Type

Successful target

[1]

Disease

[+] 2 Target-related Diseases

Glaucoma [ICD-11: 9C61]

Myocardial infarction [ICD-11: BA41-BA43]

UniProt ID

NOUNIPROTAC

Drugs and Modes of Action

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Approved Drug(s)

[+] 2 Approved Drugs

Netarsudil

Drug Info

Approved

Open-angle glaucoma

[2]

Ximelegatran

Drug Info

Approved

Myocardial infarction

[3]

Clinical Trial Drug(s)

[+] 7 Clinical Trial Drugs

Roclatan

Drug Info

Phase 3

Glaucoma/ocular hypertension

[4]

AMA-76

Drug Info

Phase 2

Glaucoma/ocular hypertension

[5]

AR-12286

Drug Info

Phase 2

Glaucoma/ocular hypertension

[6]

Cethrin

Drug Info

Phase 1/2

Spinal cord injury

[7]

Y-39983

Drug Info

Phase 1/2

Glaucoma/ocular hypertension

[8]

AT13148

Drug Info

Phase 1

Solid tumour/cancer

[9]

STM 434

Drug Info

Phase 1

Ovarian cancer

[10]

Mode of Action

[+] 2 Modes of Action

Modulator

[+] 8 Modulator drugs

Netarsudil

Drug Info

[11]

Ximelegatran

Drug Info

[1], [12]

Roclatan

Drug Info

[13]

AMA-76

Drug Info

[14]

AR-12286

Drug Info

[15]

Cethrin

Drug Info

[16]

Y-39983

Drug Info

[17]

AT13148

Drug Info

[18]

Inhibitor

[+] 9 Inhibitor drugs

STM 434

Drug Info

[19]

Hexahydro azepinone derivative 1

Drug Info

[19]

Isoquinoline derivative 4

Drug Info

[19]

Isoquinoline derivative 5

Drug Info

[19]

Isoquinoline sulfonamide derivative 1

Drug Info

[19]

Isoquinoline sulfonamide derivative 2

Drug Info

[19]

Isoquinoline sulfonyl derivative 1

Drug Info

[19]

Isoquinoline sulfonyl derivative 2

Drug Info

[19]

Isoquinoline sulfonyl derivative 3

Drug Info

[19]

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(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's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

References

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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.

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