Target Information
| Target General Information | Top | |||||
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| Target ID |
T85421
(Former ID: TTDR00289)
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| Target Name |
Jun N terminal kinase (JNK)
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| Synonyms |
c-Jun N-terminal kinase; Stress-activated protein kinase JNK; SAPK1; PRKM; MAP kinase; JNK
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| Gene Name |
MAPK8; MAPK9; MAPK10
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Dissociative neurological symptom disorder [ICD-11: 6B60] | |||||
| Function |
Associates with scaffold proteins JNK interacting proteins as well as their upstream kinases JNKK1 and JNKK2 following their activation. Modifies the activity of numerous proteins that reside at the mitochondria or act in the nucleus. Downstream molecules that are activated by JNK include c-Jun, ATF2, ELK1, SMAD4, p53 and HSF1. Involved in apoptosis, neurodegeneration, cell differentiation and proliferation, inflammatory conditions and cytokine production mediated by AP-1 (activation protein 1) such as RANTES, IL-8 and GM-CSF.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| Sequence |
MSRSKRDNNFYSVEIGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAILERNVAIKKLSRP
FQNQTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQ MELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSF MMTPYVVTRYYRAPEVILGMGYKENVDLWSVGCIMGEMVCHKILFPGRDYIDQWNKVIEQ LGTPCPEFMKKLQPTVRTYVENRPKYAGYSFEKLFPDVLFPADSEHNKLKASQARDLLSK MLVIDASKRISVDEALQHPYINVWYDPSEAEAPPPKIPDKQLDEREHTIEEWKELIYKEV MDLEERTKNGVIRGQPSPLGAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAA GPLGCCR Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
| 1 | AM-111 | Drug Info | Phase 3 | Neurological disorder | [2] | |
| 2 | BGP-15 | Drug Info | Phase 2 | Type-2 diabetes | [1], [3], [4] | |
| 3 | CC-401 | Drug Info | Phase 2 | Solid tumour/cancer | [5] | |
| 4 | CC-930 | Drug Info | Phase 2 | Discoid lupus erythematosus | [6], [7] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 3 Modulator drugs | + | ||||
| 1 | AM-111 | Drug Info | [8] | |||
| 2 | CC-401 | Drug Info | [9], [10] | |||
| 3 | CC-930 | Drug Info | [11] | |||
| Inhibitor | [+] 4 Inhibitor drugs | + | ||||
| 1 | BGP-15 | Drug Info | [1] | |||
| 2 | PMID25991433-Compound-O1 | Drug Info | [12] | |||
| 3 | PMID25991433-Compound-Q1 | Drug Info | [12] | |||
| 4 | 2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One | Drug Info | [13] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "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 | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| References | Top | |||||
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| REF 1 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 2 | ClinicalTrials.gov (NCT02235272) Efficacy and Safety of XG-102 in Reduction of Post-cataract Surgery Intraocular Inflammation. U.S. National Institutes of Health. | |||||
| REF 3 | BGP-15, a PARP-inhibitor, prevents imatinib-induced cardiotoxicity by activating Akt and suppressing JNK and p38 MAP kinases. Mol Cell Biochem. 2012 Jun;365(1-2):129-37. | |||||
| REF 4 | BGP-15 - a novel poly(ADP-ribose) polymerase inhibitor - protects against nephrotoxicity of cisplatin without compromising its antitumor activity. Biochem Pharmacol. 2002 Mar 15;63(6):1099-111. | |||||
| REF 5 | SP600125 inhibits Orthopoxviruses replication in a JNK1/2 -independent manner: Implication as a potential antipoxviral. Antiviral Res. 2012 Jan;93(1):69-77. | |||||
| REF 6 | ClinicalTrials.gov (NCT01203943) A Study to Characterize the Safety, PK and Biological Activity of CC-930 in Idiopathic Pulmonary Fibrosis (IPF). U.S. National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.gov (NCT01466725) A Research Study to Assess if CC-930 is Safe in Treating Subjects With Discoid Lupus Erythematosus. U.S. National Institutes of Health. | |||||
| REF 8 | The JNK inhibitor XG-102 protects against TNBS-induced colitis.PLoS One.2012;7(3):e30985. | |||||
| REF 9 | Signal integration by JNK and p38 MAPK pathways in cancer development.Nat Rev Cancer.2009 Aug;9(8):537-49. | |||||
| REF 10 | Recent progress in the design, study, and development of c-Jun N-terminal kinase inhibitors as anticancer agents.Chem Biol.2014 Nov 20;21(11):1433-43. | |||||
| REF 11 | In vitro metabolism of a novel JNK inhibitor tanzisertib: interspecies differences in oxido-reduction and characterization of enzymes involved in metabolism. Xenobiotica. 2015;45(6):465-80. | |||||
| REF 12 | c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72. | |||||
| REF 13 | c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J Clin Invest. 2001 Jul;108(1):73-81. | |||||
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