Target Information
| Target General Infomation | |||||
|---|---|---|---|---|---|
| Target ID |
T14731
|
||||
| Former ID |
TTDC00052
|
||||
| Target Name |
NAD-dependent deacetylase sirtuin-1
|
||||
| Gene Name |
SIRT1
|
||||
| Synonyms |
SIR2-like protein 1; SIR2L1; hSIR2; hSIRT1; SIRT1
|
||||
| Target Type |
Clinical Trial
|
||||
| Disease | Colon cancer; Hematologic cancers; Type 2 diabetes [ICD9: 140-229, 250, 250.00, 250.02; ICD10: E08-E13, E11] | ||||
| Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
| Chronic obstructive pulmonary disease [ICD9: 490-492, 494-496; ICD10: J40-J44, J47] | |||||
| Huntington's disease [ICD9: 294.1, 333.4; ICD10: F02.2, G10] | |||||
| Obesity [ICD9: 278; ICD10: E66] | |||||
| Type 2 diabetes [ICD9: 250; ICD10: E11] | |||||
| Function |
SirtT1 75 kDa fragment: catalytically inactive 75SirT1 may be involved in regulation of apoptosis. May be involved in protecting chondrocytes from apoptotic death by associating with cytochrome C and interfering with apoptosome assembly.
|
||||
| BioChemical Class |
Carbon-nitrogen hydrolase
|
||||
| Target Validation |
T14731
|
||||
| UniProt ID | |||||
| EC Number |
EC 3.5.1.-
|
||||
| Sequence |
MADEAALALQPGGSPSAAGADREAASSPAGEPLRKRPRRDGPGLERSPGEPGGAAPEREV
PAAARGCPGAAAAALWREAEAEAAAAGGEQEAQATAAAGEGDNGPGLQGPSREPPLADNL YDEDDDDEGEEEEEAAAAAIGYRDNLLFGDEIITNGFHSCESDEEDRASHASSSDWTPRP RIGPYTFVQQHLMIGTDPRTILKDLLPETIPPPELDDMTLWQIVINILSEPPKRKKRKDI NTIEDAVKLLQECKKIIVLTGAGVSVSCGIPDFRSRDGIYARLAVDFPDLPDPQAMFDIE YFRKDPRPFFKFAKEIYPGQFQPSLCHKFIALSDKEGKLLRNYTQNIDTLEQVAGIQRII QCHGSFATASCLICKYKVDCEAVRGDIFNQVVPRCPRCPADEPLAIMKPEIVFFGENLPE QFHRAMKYDKDEVDLLIVIGSSLKVRPVALIPSSIPHEVPQILINREPLPHLHFDVELLG DCDVIINELCHRLGGEYAKLCCNPVKLSEITEKPPRTQKELAYLSELPPTPLHVSEDSSS PERTSPPDSSVIVTLLDQAAKSNDDLDVSESKGCMEEKPQEVQTSRNVESIAEQMENPDL KNVGSSTGEKNERTSVAGTVRKCWPNRVAKEQISRRLDGNQYLFLPPNRYIFHGAEVYSD SEDDVLSSSSCGSNSDSGTCQSPSLEEPMEDESEIEEFYNGLEDEPDVPERAGGAGFGTD GDDQEAINEAISVKQEVTDMNYPSNKS |
||||
| Drugs and Mode of Action | |||||
| Drug(s) | GSK2245840 | Drug Info | Phase 2 | Chronic obstructive pulmonary disease | [1] |
| MB-12066 | Drug Info | Phase 2 | Obesity | [2] | |
| SEN-196 | Drug Info | Phase 2 | Huntington's disease | [3], [4] | |
| SRT2379 | Drug Info | Phase 1 | Type 2 diabetes | [5] | |
| SRT3025 | Drug Info | Phase 1 | Type 2 diabetes | [6] | |
| GSK184072 | Drug Info | Discontinued in Phase 2 | Colon cancer; Hematologic cancers; Type 2 diabetes | [7] | |
| Inhibitor | (R)-sirtinol | Drug Info | [8] | ||
| (S)-sirtinol | Drug Info | [8] | |||
| 2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide | Drug Info | [9] | |||
| 2H-chromeno[2,3-d]pyrimidine-2,4(3H)-dione | Drug Info | [10] | |||
| BISINDOLYLMALEIMIDE IX | Drug Info | [11] | |||
| CAMBINOL | Drug Info | [12] | |||
| Meta-sirtinol | Drug Info | [8] | |||
| Para-sirtinol | Drug Info | [8] | |||
| RO-316233 | Drug Info | [11] | |||
| SEN-196 | Drug Info | [13] | |||
| splitomicin | Drug Info | [10] | |||
| YK-3237 | Drug Info | [14] | |||
| Activator | GSK184072 | Drug Info | [15] | ||
| SRT1720 | Drug Info | [16] | |||
| Modulator | GSK2245840 | Drug Info | [17], [18] | ||
| MB-12066 | Drug Info | ||||
| SRT2379 | Drug Info | [19] | |||
| SRT3025 | Drug Info | [20] | |||
| Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
| TEP | EXP Info | ||||
| Pathways | |||||
| KEGG Pathway | FoxO signaling pathway | ||||
| AMPK signaling pathway | |||||
| Glucagon signaling pathway | |||||
| Amphetamine addiction | |||||
| MicroRNAs in cancer | |||||
| PANTHER Pathway | p53 pathway | ||||
| Pathway Interaction Database | p73 transcription factor network | ||||
| Signaling events mediated by HDAC Class III | |||||
| E2F transcription factor network | |||||
| HIF-2-alpha transcription factor network | |||||
| Signaling events mediated by HDAC Class I | |||||
| FoxO family signaling | |||||
| Regulation of Androgen receptor activity | |||||
| Regulation of retinoblastoma protein | |||||
| Reactome | RORA activates gene expression | ||||
| Regulation of HSF1-mediated heat shock response | |||||
| Circadian Clock | |||||
| WikiPathways | Integrated Pancreatic Cancer Pathway | ||||
| SREBF and miR33 in cholesterol and lipid homeostasis | |||||
| Integrated Breast Cancer Pathway | |||||
| SREBP signalling | |||||
| Androgen receptor signaling pathway | |||||
| References | |||||
| REF 1 | ClinicalTrials.gov (NCT01154101) Study of the Clinical Activity, Safety, and Tolerability of SRT2104 in Subjects With Moderate to Severe Plaque-Type Psoriasis. U.S. National Institutes of Health. | ||||
| REF 2 | ClinicalTrials.gov (NCT02029586) Therapeutic Exploratory Phase 2 Study to Evaluate the Safety and Efficacy of MB12066 in Patients With Nonalcoholic Fatty Liver Disease(NAFLD) Except Cirrhosis. U.S. National Institutes of Health. | ||||
| REF 3 | ClinicalTrials.gov (NCT01521585) A Phase II Safety and Tolerability Study With SEN0014196. U.S. National Institutes of Health. | ||||
| REF 4 | (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: 8100). | ||||
| REF 5 | ClinicalTrials.gov (NCT01018628) A Clinical Study to Assess the Safety and Pharmacokinetics of SRT2379 in Normal Healthy Male Volunteers. U.S. National Institutes of Health. | ||||
| REF 6 | ClinicalTrials.gov (NCT01340911) A Study in Healthy Male Volunteers to Investigate Different Doses of a New Drug for the Treatment of Metabolic Diseases. U.S. National Institutes of Health. | ||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024569) | ||||
| REF 8 | J Med Chem. 2005 Dec 1;48(24):7789-95.Design, synthesis, and biological evaluation of sirtinol analogues as class III histone/protein deacetylase (Sirtuin) inhibitors. | ||||
| REF 9 | J Med Chem. 2005 Dec 15;48(25):8045-54.Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1. | ||||
| REF 10 | J Med Chem. 2010 Feb 11;53(3):1407-11.Characterization of sirtuin inhibitors in nematodes expressing a muscular dystrophy protein reveals muscle cell and behavioral protection by specific sirtinol analogues. | ||||
| REF 11 | J Med Chem. 2006 Dec 14;49(25):7307-16.Adenosine mimetics as inhibitors of NAD+-dependent histone deacetylases, from kinase to sirtuin inhibition. | ||||
| REF 12 | J Med Chem. 2009 May 14;52(9):2673-82.Novel cambinol analogs as sirtuin inhibitors: synthesis, biological evaluation, and rationalization of activity. | ||||
| REF 13 | Sirtuin 1 (SIRT1): the misunderstood HDAC. J Biomol Screen. 2011 Dec;16(10):1153-69. | ||||
| REF 14 | (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: 2707). | ||||
| REF 15 | Clinical pipeline report, company report or official report of GlaxoSmithKline (2009). | ||||
| REF 16 | Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007 Nov 29;450(7170):712-6. | ||||
| REF 17 | Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease. Expert Opin Investig Drugs. 2015 Mar;24(3):283-307. | ||||
| REF 18 | Sirtuin 1 activator SRT2104 protects Huntington's disease mice. Ann Clin Transl Neurol. 2014 Dec;1(12):1047-52. | ||||
| REF 19 | SRT2379, a small-molecule SIRT1 activator, fails to reduce cytokine release in a human endotoxemia model. Critical Care 2013, 17(Suppl 4):P8. | ||||
| REF 20 | The Sirt1 Activators SRT2183 and SRT3025 Inhibit RANKL-Induced Osteoclastogenesis in Bone Marrow-Derived Macrophages and Down-Regulate Sirt3 in Sirt1 Null Cells. PLoS One. 2015 Jul 30;10(7):e0134391. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.