Target Information
| Target General Information | Top | |||||
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| Target ID |
T86052
(Former ID: TTDC00195)
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| Target Name |
Telomerase reverse transcriptase (TERT)
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| Synonyms |
Telomerase-associated protein 2; Telomerase catalytic subunit; TRT; TP2; TCS1; HEST2; EST2
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| Gene Name |
TERT
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Pancreatic cancer [ICD-11: 2C10] | |||||
| 2 | Myelodysplastic syndrome [ICD-11: 2A37] | |||||
| Function |
Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal somatic cells. Catalytic component of the teleromerase holoenzyme complex whose main activity is the elongation of telomeres by acting as a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. Catalyzes the RNA-dependent extension of 3'-chromosomal termini with the 6-nucleotide telomeric repeat unit, 5'-TTAGGG-3'. The catalytic cycle involves primer binding, primer extension and release of product once the template boundary has been reached or nascent product translocation followed by further extension. More active on substrates containing 2 or 3 telomeric repeats. Telomerase activity is regulated by a number of factors including telomerase complex-associated proteins, chaperones and polypeptide modifiers. Modulates Wnt signaling. Plays important roles in aging and antiapoptosis.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.7.49
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| Sequence |
MPRAPRCRAVRSLLRSHYREVLPLATFVRRLGPQGWRLVQRGDPAAFRALVAQCLVCVPW
DARPPPAAPSFRQVSCLKELVARVLQRLCERGAKNVLAFGFALLDGARGGPPEAFTTSVR SYLPNTVTDALRGSGAWGLLLRRVGDDVLVHLLARCALFVLVAPSCAYQVCGPPLYQLGA ATQARPPPHASGPRRRLGCERAWNHSVREAGVPLGLPAPGARRRGGSASRSLPLPKRPRR GAAPEPERTPVGQGSWAHPGRTRGPSDRGFCVVSPARPAEEATSLEGALSGTRHSHPSVG RQHHAGPPSTSRPPRPWDTPCPPVYAETKHFLYSSGDKEQLRPSFLLSSLRPSLTGARRL VETIFLGSRPWMPGTPRRLPRLPQRYWQMRPLFLELLGNHAQCPYGVLLKTHCPLRAAVT PAAGVCAREKPQGSVAAPEEEDTDPRRLVQLLRQHSSPWQVYGFVRACLRRLVPPGLWGS RHNERRFLRNTKKFISLGKHAKLSLQELTWKMSVRDCAWLRRSPGVGCVPAAEHRLREEI LAKFLHWLMSVYVVELLRSFFYVTETTFQKNRLFFYRKSVWSKLQSIGIRQHLKRVQLRE LSEAEVRQHREARPALLTSRLRFIPKPDGLRPIVNMDYVVGARTFRREKRAERLTSRVKA LFSVLNYERARRPGLLGASVLGLDDIHRAWRTFVLRVRAQDPPPELYFVKVDVTGAYDTI PQDRLTEVIASIIKPQNTYCVRRYAVVQKAAHGHVRKAFKSHVSTLTDLQPYMRQFVAHL QETSPLRDAVVIEQSSSLNEASSGLFDVFLRFMCHHAVRIRGKSYVQCQGIPQGSILSTL LCSLCYGDMENKLFAGIRRDGLLLRLVDDFLLVTPHLTHAKTFLRTLVRGVPEYGCVVNL RKTVVNFPVEDEALGGTAFVQMPAHGLFPWCGLLLDTRTLEVQSDYSSYARTSIRASLTF NRGFKAGRNMRRKLFGVLRLKCHSLFLDLQVNSLQTVCTNIYKILLLQAYRFHACVLQLP FHQQVWKNPTFFLRVISDTASLCYSILKAKNAGMSLGAKGAAGPLPSEAVQWLCHQAFLL KLTRHRVTYVPLLGSLRTAQTQLSRKLPGTTLTALEAAANPALPSDFKTILD Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T78IOY | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 12 Clinical Trial Drugs | + | ||||
| 1 | GV1001 | Drug Info | Phase 3 | Pancreatic cancer | [2] | |
| 2 | Imetelstat | Drug Info | Phase 2/3 | Myelodysplastic syndrome | [3] | |
| 3 | CB-10-01 | Drug Info | Phase 2 | Melanoma | [4] | |
| 4 | Dendritic cell vaccine | Drug Info | Phase 2 | Ovarian cancer | [5] | |
| 5 | GRNVAC1 | Drug Info | Phase 2 | Acute myeloid leukaemia | [6] | |
| 6 | Vx-001 | Drug Info | Phase 2 | Breast cancer | [7] | |
| 7 | Epithalon | Drug Info | Phase 1/2 | Ocular inflammation | [8] | |
| 8 | OBP-301 | Drug Info | Phase 1/2 | Liver cancer | [9] | |
| 9 | DC/I540/KLH vaccine | Drug Info | Phase 1 | Brain cancer | [10] | |
| 10 | GRN163 | Drug Info | Phase 1 | Multiple myeloma | [11] | |
| 11 | KML-001 | Drug Info | Phase 1 | Solid tumour/cancer | [12] | |
| 12 | TeloB-Vax | Drug Info | Phase 1 | Prostate cancer | [13] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 9 Inhibitor drugs | + | ||||
| 1 | Berberine | Drug Info | [1] | |||
| 2 | Imetelstat | Drug Info | [3] | |||
| 3 | OBP-301 | Drug Info | [20] | |||
| 4 | GRN163 | Drug Info | [11] | |||
| 5 | KML-001 | Drug Info | [22] | |||
| 6 | 2,3,7-trichloro-5-nitroquinoxaline (TNQX) | Drug Info | [24] | |||
| 7 | PPA | Drug Info | [25] | |||
| 8 | Telomestatin | Drug Info | [11] | |||
| 9 | TMPyP4 | Drug Info | [11] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | Epithalon | Drug Info | [19] | |||
| 2 | TeloB-Vax | Drug Info | [23] | |||
| 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 | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-regulating Transcription Factors | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | IL2 Signaling Pathway | |||||
| PID Pathway | [+] 5 PID Pathways | + | ||||
| 1 | Validated targets of C-MYC transcriptional activation | |||||
| 2 | Regulation of Telomerase | |||||
| 3 | IL2 signaling events mediated by PI3K | |||||
| 4 | Regulation of nuclear beta catenin signaling and target gene transcription | |||||
| 5 | HIF-1-alpha transcription factor network | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Formation of the beta-catenin:TCF transactivating complex | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| Target QSAR Model | ||||||
| References | Top | |||||
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| REF 1 | Stage specificity of Plasmodium falciparum telomerase and its inhibition by berberine. Parasitol Int. 2002 Mar;51(1):99-103. | |||||
| REF 2 | ClinicalTrials.gov (NCT01579188) Study of the Telomerase Vaccine GV1001 to Treat Patients With Inoperable Stage III Non-small Cell Lung Cancer. U.S. National Institutes of Health. | |||||
| REF 3 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 4 | ClinicalTrials.gov (NCT00925314) A Study of Transgenic Lymphocyte Immunization (TLI) Against Telomerase in Subjects With Stage III Melanoma. U.S. National Institutes of Health. | |||||
| REF 5 | Dendritic cell-targeted vaccines--hope or hype. Nat Rev Immunol. 2014 Oct;14(10):705-11. | |||||
| REF 6 | ClinicalTrials.gov (NCT00510133) A Study of Active Immunotherapy With GRNVAC1 in Patients With Acute Myelogenous Leukemia (AML). U.S. National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.gov (NCT01935154) Efficacy Study of Vx001 Vaccine in NSCLC Patients. U.S. National Institutes of Health. | |||||
| REF 8 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021226) | |||||
| REF 9 | ClinicalTrials.gov (NCT02293850) Phase I/II Study to Evaluate the Safety and Efficacy of Telomelysin (OBP-301) in Patients With Hepatocellular Carcinoma. U.S. National Institutes of Health. | |||||
| REF 10 | Identification of an immunogenic CD8+ T-cell epitope derived from gamma-globin, a putative tumor-associated antigen for juvenile myelomonocytic leu... Blood. 2006 Oct 15;108(8):2662-8. | |||||
| REF 11 | Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127. | |||||
| REF 12 | ClinicalTrials.gov (NCT01110226) Trial Of Cisplatin And KML-001 in Platinum Responsive Malignancies. U.S. National Institutes of Health. | |||||
| REF 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034068) | |||||
| REF 14 | Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: A dose escalating phase I/II study. Br J Cancer. 2006 Dec 4;95(11):1474-82. | |||||
| REF 15 | Telomerase immunity from bench to bedside: round one. J Transl Med. 2007 Feb 26;5:12. | |||||
| REF 16 | In vitro activation of cytotoxic T-lymphocytes by hTERT-pulsed dendritic cells. J Immunotoxicol. 2009 Dec;6(4):243-8. | |||||
| REF 17 | Targeting telomerase-expressing cancer cells. J Cell Mol Med. 2011 Jul;15(7):1433-42. | |||||
| REF 18 | Clinical pipeline report, company report or official report of Vaxon-biotech. | |||||
| REF 19 | Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull Exp Biol Med. 2003 Jun;135(6):590-2. | |||||
| REF 20 | Telomerase-specific replication-selective virotherapy for human cancer. Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):285-92. | |||||
| REF 21 | Vaccination of cancer patients against telomerase induces functional antitumor CD8+ T lymphocytes. Clin Cancer Res. 2004 Feb 1;10(3):828-39. | |||||
| REF 22 | National Cancer Institute Drug Dictionary (drug id 672554). | |||||
| REF 23 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
| REF 24 | Identification of a quinoxaline derivative that is a potent telomerase inhibitor leading to cellular senescence of human cancer cells. Biochem J. 2003 Jul 15;373(Pt 2):523-9. | |||||
| REF 25 | Growth arrest, apoptosis, and telomere shortening of Barrett's-associated adenocarcinoma cells by a telomerase inhibitor. Gastroenterology. 2004 May;126(5):1337-46. | |||||
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