Target Information

Target General Infomation
Target ID
T06093
Former ID
TTDI02162
Target Name
Rho associated protein kinase 2
Gene Name
ROCK2
Synonyms
ROCK-II; Rho kinase 2; Rho-associated, coiled-coil-containing protein kinase 2; Rho-associated, coiled-coil-containing protein kinase II; p164 ROCK-2; ROCK2
Target Type
Clinical Trial
Disease Cancer [ICD9: 140-229; ICD10: C00-C96]
Chronic obstructive pulmonary disease [ICD9: 490-492, 494-496; ICD10: J40-J44, J47]
Glaucoma [ICD9: 365; ICD10: H40-H42]
Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
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.
BioChemical Class
Kinase
UniProt ID
O75116
EC Number
EC 2.7.11.1
Sequence
MSRPPPTGKMPGAPETAPGDGAGASRQRKLEALIRDPRSPINVESLLDGLNSLVLDLDFP
ALRKNKNIDNFLNRYEKIVKKIRGLQMKAEDYDVVKVIGRGAFGEVQLVRHKASQKVYAM
KLLSKFEMIKRSDSAFFWEERDIMAFANSPWVVQLFYAFQDDRYLYMVMEYMPGGDLVNL
MSNYDVPEKWAKFYTAEVVLALDAIHSMGLIHRDVKPDNMLLDKHGHLKLADFGTCMKMD
ETGMVHCDTAVGTPDYISPEVLKSQGGDGFYGRECDWWSVGVFLYEMLVGDTPFYADSLV
GTYSKIMDHKNSLCFPEDAEISKHAKNLICAFLTDREVRLGRNGVEEIRQHPFFKNDQWH
WDNIRETAAPVVPELSSDIDSSNFDDIEDDKGDVETFPIPKAFVGNQLPFIGFTYYRENL
LLSDSPSCRETDSIQSRKNEESQEIQKKLYTLEEHLSNEMQAKEELEQKCKSVNTRLEKT
AKELEEEITLRKSVESALRQLEREKALLQHKNAEYQRKADHEADKKRNLENDVNSLKDQL
EDLKKRNQNSQISTEKVNQLQRQLDETNALLRTESDTAARLRKTQAESSKQIQQLESNNR
DLQDKNCLLETAKLKLEKEFINLQSALESERRDRTHGSEIINDLQGRICGLEEDLKNGKI
LLAKVELEKRQLQERFTDLEKEKSNMEIDMTYQLKVIQQSLEQEEAEHKATKARLADKNK
IYESIEEAKSEAMKEMEKKLLEERTLKQKVENLLLEAEKRCSLLDCDLKQSQQKINELLK
QKDVLNEDVRNLTLKIEQETQKRCLTQNDLKMQTQQVNTLKMSEKQLKQENNHLMEMKMN
LEKQNAELRKERQDADGQMKELQDQLEAEQYFSTLYKTQVRELKEECEEKTKLGKELQQK
KQELQDERDSLAAQLEITLTKADSEQLARSIAEEQYSDLEKEKIMKELEIKEMMARHKQE
LTEKDATIASLEETNRTLTSDVANLANEKEELNNKLKDVQEQLSRLKDEEISAAAIKAQF
EKQLLTERTLKTQAVNKLAEIMNRKEPVKRGNDTDVRRKEKENRKLHMELKSEREKLTQQ
MIKYQKELNEMQAQIAEESQIRIELQMTLDSKDSDIEQLRSQLQALHIGLDSSSIGSGPG
DAEADDGFPESRLEGWLSLPVRNNTKKFGWVKKYVIVSSKKILFYDSEQDKEQSNPYMVL
DIDKLFHVRPVTQTDVYRADAKEIPRIFQILYANEGESKKEQEFPVEPVGEKSNYICHKG
HEFIPTLYHFPTNCEACMKPLWHMFKPPPALECRRCHIKCHKDHMDKKEEIIAPCKVYYD
ISTAKNLLLLANSTEEQQKWVSRLVKKIPKKPPAPDPFARSSPRTSMKIQQNQSIRRPSR
QLAPNKPS
Drugs and Mode of Action
Drug(s) KD025 Drug Info Phase 2 Rheumatoid arthritis [525025]
INS-117548 Drug Info Phase 1 Glaucoma [522456]
GSK269962A Drug Info Clinical trial Inflammatory disease [528461]
CDE-5110 Drug Info Terminated Inflammatory disease [548487]
Inhibitor AMA-237 Drug Info [543434]
ATS-907 Drug Info [543434]
CDE-5110 Drug Info [548488]
compound 11d Drug Info [543434]
compound 22 Drug Info [530910]
compound 32 Drug Info [530917]
compound 35 Drug Info [531084]
Glycyl-H 1152 Drug Info [527785]
GSK269962A Drug Info [528461]
KD025 Drug Info [533023]
RKI-1447 Drug Info [532172]
SR-3850 Drug Info [543434]
TRN-101 Drug Info [543434]
Modulator INS-117548 Drug Info [1572591]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway cGMP-PKG signaling pathway
cAMP signaling pathway
Chemokine signaling pathway
Sphingolipid signaling pathway
Vascular smooth muscle contraction
Wnt signaling pathway
Axon guidance
Focal adhesion
Platelet activation
Leukocyte transendothelial migration
Regulation of actin cytoskeleton
Oxytocin signaling pathway
Pathogenic Escherichia coli infection
Shigellosis
Salmonella infection
Pathways in cancer
Proteoglycans in cancer
PANTHER Pathway Cytoskeletal regulation by Rho GTPase
Pathway Interaction Database RhoA signaling pathway
Plasma membrane estrogen receptor signaling
Osteopontin-mediated events
PLK1 signaling events
PAR4-mediated thrombin signaling events
PAR1-mediated thrombin signaling events
Signaling events mediated by focal adhesion kinase
Reactome EPHB-mediated forward signaling
EPHA-mediated growth cone collapse
G alpha (12/13) signalling events
Sema4D induced cell migration and growth-cone collapse
VEGFA-VEGFR2 Pathway
RHO GTPases Activate ROCKs
WikiPathways G13 Signaling Pathway
Regulation of Actin Cytoskeleton
Focal Adhesion
JAK/STAT
Spinal Cord Injury
Pathogenic Escherichia coli infection
Leptin signaling pathway
Semaphorin interactions
Integrin-mediated Cell Adhesion
GPCR downstream signaling
MicroRNAs in cardiomyocyte hypertrophy
Androgen receptor signaling pathway
References
Ref 522456ClinicalTrials.gov (NCT00767793) A Placebo-Controlled Study of INS117548 Ophthalmic Solution in Subjects With Glaucoma (P08650). U.S. National Institutes of Health.
Ref 525025ClinicalTrials.gov (NCT02317627) Study of of KD025 in Subjects With Psoriasis Vulgaris Who Failed First-Line Therapy. U.S. National Institutes of Health.
Ref 528461Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. 2007 Jan;320(1):89-98. Epub 2006 Oct 3.
Ref 548487Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025959)
Ref
Ref 527785Development of specific Rho-kinase inhibitors and their clinical application. Biochim Biophys Acta. 2005 Dec 30;1754(1-2):245-52. Epub 2005 Sep 12.
Ref 528461Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. 2007 Jan;320(1):89-98. Epub 2006 Oct 3.
Ref 530910Substituted 2H-isoquinolin-1-one as potent Rho-Kinase inhibitors. Part 1: Hit-to-lead account. Bioorg Med Chem Lett. 2010 Jun 1;20(11):3235-9.
Ref 530917Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: part 3, aryl substituted pyrrolidines. Bioorg Med Chem Lett. 2010 Jun 15;20(12):3746-9.
Ref 531084Tetrahydroisoquinoline derivatives as highly selective and potent Rho kinase inhibitors. J Med Chem. 2010 Aug 12;53(15):5727-37.
Ref 532172Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2). Medchemcomm. 2012 Jun 1;3(6):699-709. Epub 2012 Jan 27.
Ref 533023Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism. Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16814-9.
Ref 543434(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1504).
Ref 548488Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025959)
Ref 1572591Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.