Target Information
Target General Infomation | |||||
---|---|---|---|---|---|
Target ID |
T07102
|
||||
Former ID |
TTDC00202
|
||||
Target Name |
Rho-associated protein kinase 1
|
||||
Gene Name |
ROCK1
|
||||
Synonyms |
Let-502 kinase; P160 ROCK-1; P160(rock); P160ROCK; ROCK; Rho kinase; Rho-associated kinase; Rho-associated protein kinase; Rho-associated, coiled-coil containing protein kinase; Rho-associated, coiled-coil containing protein kinase 1; Rok; ROCK1
|
||||
Target Type |
Clinical Trial
|
||||
Disease | Atherosclerosis [ICD9: 414.0, 440; ICD10: I70] | ||||
Chronic obstructive pulmonary disease [ICD9: 490-492, 494-496; ICD10: J40-J44, J47] | |||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
Diabetic nephropathy [ICD9: 250.4; ICD10: E11.21] | |||||
Glaucoma [ICD9: 365; ICD10: H40-H42] | |||||
Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25] | |||||
Pulmonary arterial hypertension [ICD9: 416; ICD10: I27.0, I27.2] | |||||
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89] | |||||
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 DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, PFN1 and PPP1R12A. Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing. Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress. Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis. Plays a role in terminal erythroid differentiation. May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles. Promotes keratinocyte terminal differentiation. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization.
|
||||
BioChemical Class |
Kinase
|
||||
Target Validation |
T07102
|
||||
UniProt ID | |||||
EC Number |
EC 2.7.11.1
|
||||
Sequence |
MSTGDSFETRFEKMDNLLRDPKSEVNSDCLLDGLDALVYDLDFPALRKNKNIDNFLSRYK
DTINKIRDLRMKAEDYEVVKVIGRGAFGEVQLVRHKSTRKVYAMKLLSKFEMIKRSDSAF FWEERDIMAFANSPWVVQLFYAFQDDRYLYMVMEYMPGGDLVNLMSNYDVPEKWARFYTA EVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGTCMKMNKEGMVRCDTAVGTPDY ISPEVLKSQGGDGYYGRECDWWSVGVFLYEMLVGDTPFYADSLVGTYSKIMNHKNSLTFP DDNDISKEAKNLICAFLTDREVRLGRNGVEEIKRHLFFKNDQWAWETLRDTVAPVVPDLS SDIDTSNFDDLEEDKGEEETFPIPKAFVGNQLPFVGFTYYSNRRYLSSANPNDNRTSSNA DKSLQESLQKTIYKLEEQLHNEMQLKDEMEQKCRTSNIKLDKIMKELDEEGNQRRNLEST VSQIEKEKMLLQHRINEYQRKAEQENEKRRNVENEVSTLKDQLEDLKKVSQNSQLANEKL SQLQKQLEEANDLLRTESDTAVRLRKSHTEMSKSISQLESLNRELQERNRILENSKSQTD KDYYQLQAILEAERRDRGHDSEMIGDLQARITSLQEEVKHLKHNLEKVEGERKEAQDMLN HSEKEKNNLEIDLNYKLKSLQQRLEQEVNEHKVTKARLTDKHQSIEEAKSVAMCEMEKKL KEEREAREKAENRVVQIEKQCSMLDVDLKQSQQKLEHLTGNKERMEDEVKNLTLQLEQES NKRLLLQNELKTQAFEADNLKGLEKQMKQEINTLLEAKRLLEFELAQLTKQYRGNEGQMR ELQDQLEAEQYFSTLYKTQVKELKEEIEEKNRENLKKIQELQNEKETLATQLDLAETKAE SEQLARGLLEEQYFELTQESKKAASRNRQEITDKDHTVSRLEEANSMLTKDIEILRRENE ELTEKMKKAEEEYKLEKEEEISNLKAAFEKNINTERTLKTQAVNKLAEIMNRKDFKIDRK KANTQDLRKKEKENRKLQLELNQEREKFNQMVVKHQKELNDMQAQLVEECAHRNELQMQL ASKESDIEQLRAKLLDLSDSTSVASFPSADETDGNLPESRIEGWLSVPNRGNIKRYGWKK QYVVVSSKKILFYNDEQDKEQSNPSMVLDIDKLFHVRPVTQGDVYRAETEEIPKIFQILY ANEGECRKDVEMEPVQQAEKTNFQNHKGHEFIPTLYHFPANCDACAKPLWHVFKPPPALE CRRCHVKCHRDHLDKKEDLICPCKVSYDVTSARDMLLLACSQDEQKKWVTHLVKKIPKNP PSGFVRASPRTLSTRSTANQSFRKVVKNTSGKTS |
||||
Drugs and Mode of Action | |||||
Drug(s) | Fasudil | Drug Info | Phase 3 | Discovery agent | [468243], [522059] |
CI-1040 | Drug Info | Phase 2 | Discovery agent | [521505], [541019] | |
H-1152 | Drug Info | Phase 2 | Pulmonary arterial hypertension | [544408] | |
SAR-407899 | Drug Info | Phase 2 | Diabetic nephropathy | [522687] | |
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 | (4-Fluoro-phenyl)-(9H-purin-6-yl)-amine | Drug Info | [527421] | ||
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole | Drug Info | [527308] | |||
5-(1,4-DIAZEPAN-1-SULFONYL)ISOQUINOLINE | Drug Info | [551374] | |||
AMA-237 | Drug Info | [543433] | |||
AS-1892802 | Drug Info | [543433] | |||
ATS-907 | Drug Info | [543433] | |||
BISINDOLYLMALEIMIDE IX | Drug Info | [525872] | |||
CDE-5110 | Drug Info | [548488] | |||
CI-1040 | Drug Info | [525872] | |||
compound 22 | Drug Info | [530910] | |||
compound 33 | Drug Info | [530078] | |||
compound 35 | Drug Info | [531084] | |||
Fasudil | Drug Info | [535190] | |||
GF-109203 | Drug Info | [525872] | |||
GSK269962A | Drug Info | [528461] | |||
H-1152 | Drug Info | [536294] | |||
H-1152P | Drug Info | [535541] | |||
Hydroxyfasudil | Drug Info | [535867] | |||
KN-62 | Drug Info | [525872] | |||
KT-5720 | Drug Info | [525872] | |||
RKI-1447 | Drug Info | [532172] | |||
RO-316233 | Drug Info | [525872] | |||
ROCK-1 inhibitors | Drug Info | [543433] | |||
SAR-407899 | Drug Info | [531827] | |||
SB-747651A | Drug Info | [529701] | |||
SR-3850 | Drug Info | [543433] | |||
TRN-101 | Drug Info | [543433] | |||
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 | |||||
TGF-beta 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 | |||||
MicroRNAs in cancer | |||||
PANTHER Pathway | Cytoskeletal regulation by Rho GTPase | ||||
Inflammation mediated by chemokine and cytokine signaling pathway | |||||
CCKR signaling map ST | |||||
Pathway Interaction Database | Signaling events mediated by PRL | ||||
RhoA signaling pathway | |||||
Noncanonical Wnt signaling pathway | |||||
EPHB forward signaling | |||||
Thromboxane A2 receptor signaling | |||||
PAR4-mediated thrombin signaling events | |||||
amb2 Integrin signaling | |||||
Integrins in angiogenesis | |||||
EPHA forward signaling | |||||
Stabilization and expansion of the E-cadherin adherens junction | |||||
Signaling events mediated by VEGFR1 and VEGFR2 | |||||
PAR1-mediated thrombin signaling events | |||||
N-cadherin signaling events | |||||
Reactome | Apoptotic cleavage of cellular proteins | ||||
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 | |||||
EGF/EGFR Signaling Pathway | |||||
TGF beta Signaling Pathway | |||||
Focal Adhesion | |||||
JAK/STAT | |||||
AGE/RAGE pathway | |||||
Pathogenic Escherichia coli infection | |||||
Regulation of Microtubule Cytoskeleton | |||||
Leptin signaling pathway | |||||
Semaphorin interactions | |||||
Integrin-mediated Cell Adhesion | |||||
GPCR downstream signaling | |||||
Apoptotic execution phase | |||||
MicroRNAs in cardiomyocyte hypertrophy | |||||
Androgen receptor signaling pathway | |||||
References | |||||
Ref 468243 | (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. (Ligand id: 5181). | ||||
Ref 521505 | ClinicalTrials.gov (NCT00033384) CI-1040 in Treating Patients With Advanced Breast, Colon, Pancreatic, or Non-Small Cell Lung Cancer. U.S. National Institutes of Health. | ||||
Ref 522059 | ClinicalTrials.gov (NCT00498615) A Rho-kinase Inhibitor (Fasudil) in the Treatment of Raynaud's Phenomenon. U.S. National Institutes of Health. | ||||
Ref 522456 | ClinicalTrials.gov (NCT00767793) A Placebo-Controlled Study of INS117548 Ophthalmic Solution in Subjects With Glaucoma (P08650). U.S. National Institutes of Health. | ||||
Ref 522687 | ClinicalTrials.gov (NCT00914277) SAR407899 Single-dose in Treatment of Mild to Moderate Erectile Dysfunction. U.S. National Institutes of Health. | ||||
Ref 528461 | Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. 2007 Jan;320(1):89-98. Epub 2006 Oct 3. | ||||
Ref 541019 | (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. (Ligand id: 5676). | ||||
Ref 525872 | Biochem J. 2000 Oct 1;351(Pt 1):95-105.Specificity and mechanism of action of some commonly used protein kinase inhibitors. | ||||
Ref 527308 | J Med Chem. 2004 Dec 2;47(25):6239-47.Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. | ||||
Ref 527421 | J Med Chem. 2005 Feb 10;48(3):710-22.Synthesis and biological testing of purine derivatives as potential ATP-competitive kinase inhibitors. | ||||
Ref 528461 | Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. 2007 Jan;320(1):89-98. Epub 2006 Oct 3. | ||||
Ref 529701 | J Med Chem. 2008 Sep 25;51(18):5663-79.Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase. | ||||
Ref 530078 | Identification and SAR of squarate inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). Bioorg Med Chem. 2009 May 1;17(9):3342-51. | ||||
Ref 530910 | Substituted 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 531084 | Tetrahydroisoquinoline derivatives as highly selective and potent Rho kinase inhibitors. J Med Chem. 2010 Aug 12;53(15):5727-37. | ||||
Ref 531827 | The Rho kinase inhibitor SAR407899 potently inhibits endothelin-1-induced constriction of renal resistance arteries. J Hypertens. 2012 May;30(5):980-9. | ||||
Ref 532172 | Pyridylthiazole-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 535190 | Long-term inhibition of Rho-kinase induces a regression of arteriosclerotic coronary lesions in a porcine model in vivo. Cardiovasc Res. 2001 Jul;51(1):169-77. | ||||
Ref 535541 | The novel and specific Rho-kinase inhibitor (S)-(+)-2-methyl-1-[(4-methyl-5-isoquinoline)sulfonyl]-homopiperazine as a probing molecule for Rho-kinase-involved pathway. Pharmacol Ther. 2002 Feb-Mar;93(2-3):225-32. | ||||
Ref 535867 | Long-term treatment with a specific Rho-kinase inhibitor suppresses cardiac allograft vasculopathy in mice. Circ Res. 2004 Jan 9;94(1):46-52. Epub 2003 Nov 13. | ||||
Ref 536294 | Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19. | ||||
Ref 543433 | (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: 1503). |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.