Target Information

Target General Infomation
Target ID
T86052
Former ID
TTDC00195
Target Name
Telomerase reverse transcriptase
Gene Name
TERT
Synonyms
HEST2; TP2; Telomerase catalytic subunit; Telomerase reverse transcriptase; Telomerase-associated protein 2; TERT
Target Type
Clinical Trial
Disease Acute myeloid leukemia [ICD9: 205; ICD10: C92.0]
Brain cancer [ICD9: 191, 225.0; ICD10: C71, D33]
Breast cancer; Head and neck cancer; Liver cancer [ICD9:174, 175, 140-149, 140-229, 155, 203.0; ICD10: C50, C07-C14, C32-C33, C22]
Melanoma [ICD9: 172; ICD10: C43]
Multiple myeloma [ICD9: 203; ICD10: C90]
Ocular inflammation [ICD9: 370.33; ICD10: H16.229]
Ovarian cancer [ICD9: 183; ICD10: C56]
Pancreatic cancer [ICD9: 140-199, 140-229, 157, 210-229; ICD10: C25]
Prostate cancer [ICD9: 185; ICD10: C61]
Function
Telomerase is a ribonucleoprotein enzyme essential forthe 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 RNAcomponent 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 inaging and antiapoptosis.
BioChemical Class
Nucleotidyltransferase
Target Validation
T86052
UniProt ID
O14746
EC Number
EC 2.7.7.49
Sequence
MPRAPRCRAVRSLLRSHYREVLPLATFVRRLGPQGWRLVQRGDPAAFRALVAQCLVCVPW
DARPPPAAPSFRQVSCLKELVARVLQRLCERGAKNVLAFGFALLDGARGGPPEAFTTSVR
SYLPNTVTDALRGSGAWGLLLRRVGDDVLVHLLARCALFVLVAPSCAYQVCGPPLYQLGA
ATQARPPPHASGPRRRLGCERAWNHSVREAGVPLGLPAPGARRRGGSASRSLPLPKRPRR
GAAPEPERTPVGQGSWAHPGRTRGPSDRGFCVVSPARPAEEATSLEGALSGTRHSHPSVG
RQHHAGPPSTSRPPRPWDTPCPPVYAETKHFLYSSGDKEQLRPSFLLSSLRPSLTGARRL
VETIFLGSRPWMPGTPRRLPRLPQRYWQMRPLFLELLGNHAQCPYGVLLKTHCPLRAAVT
PAAGVCAREKPQGSVAAPEEEDTDPRRLVQLLRQHSSPWQVYGFVRACLRRLVPPGLWGS
RHNERRFLRNTKKFISLGKHAKLSLQELTWKMSVRDCAWLRRSPGVGCVPAAEHRLREEI
LAKFLHWLMSVYVVELLRSFFYVTETTFQKNRLFFYRKSVWSKLQSIGIRQHLKRVQLRE
LSEAEVRQHREARPALLTSRLRFIPKPDGLRPIVNMDYVVGARTFRREKRAERLTSRVKA
LFSVLNYERARRPGLLGASVLGLDDIHRAWRTFVLRVRAQDPPPELYFVKVDVTGAYDTI
PQDRLTEVIASIIKPQNTYCVRRYAVVQKAAHGHVRKAFKSHVSTLTDLQPYMRQFVAHL
QETSPLRDAVVIEQSSSLNEASSGLFDVFLRFMCHHAVRIRGKSYVQCQGIPQGSILSTL
LCSLCYGDMENKLFAGIRRDGLLLRLVDDFLLVTPHLTHAKTFLRTLVRGVPEYGCVVNL
RKTVVNFPVEDEALGGTAFVQMPAHGLFPWCGLLLDTRTLEVQSDYSSYARTSIRASLTF
NRGFKAGRNMRRKLFGVLRLKCHSLFLDLQVNSLQTVCTNIYKILLLQAYRFHACVLQLP
FHQQVWKNPTFFLRVISDTASLCYSILKAKNAGMSLGAKGAAGPLPSEAVQWLCHQAFLL
KLTRHRVTYVPLLGSLRTAQTQLSRKLPGTTLTALEAAANPALPSDFKTILD
Structure
2BCK; 4B18; 4MNQ
Drugs and Mode of Action
Drug(s) Berberine Drug Info Phase 4 Discovery agent [524081]
GV1001 Drug Info Phase 3 Pancreatic cancer [523876]
CB-10-01 Drug Info Phase 2 Melanoma [522705]
Dendritic cell vaccine Drug Info Phase 2 Ovarian cancer [532941]
GRNVAC1 Drug Info Phase 2 Acute myeloid leukemia [522080]
Epithalon Drug Info Phase 1/2 Ocular inflammation [548016]
OBP-301 Drug Info Phase 1/2 Breast cancer; Head and neck cancer; Liver cancer [525003]
DC/I540/KLH vaccine Drug Info Phase 1 Brain cancer [528257]
GRN163 Drug Info Phase 1 Multiple myeloma [537114]
TeloB-Vax Drug Info Phase 1 Prostate cancer [549237]
Inhibitor 2,3,7-trichloro-5-nitroquinoxaline (TNQX) Drug Info [535725]
Berberine Drug Info [535389]
GRN163 Drug Info [537114]
OBP-301 Drug Info [526935]
PPA Drug Info [535961]
Telomestatin Drug Info [537114]
TMPyP4 Drug Info [537114]
Modulator Epithalon Drug Info [526699]
TeloB-Vax Drug Info [1572591]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
NetPath Pathway IL2 Signaling Pathway
Pathway Interaction Database Validated targets of C-MYC transcriptional activation
Regulation of Telomerase
IL2 signaling events mediated by PI3K
Regulation of nuclear beta catenin signaling and target gene transcription
HIF-1-alpha transcription factor network
Reactome TCF transactivating complex
References
Ref 522080ClinicalTrials.gov (NCT00510133) A Study of Active Immunotherapy With GRNVAC1 in Patients With Acute Myelogenous Leukemia (AML). U.S. National Institutes of Health.
Ref 522705ClinicalTrials.gov (NCT00925314) A Study of Transgenic Lymphocyte Immunization (TLI) Against Telomerase in Subjects With Stage III Melanoma. U.S. National Institutes of Health.
Ref 523876ClinicalTrials.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 524081ClinicalTrials.gov (NCT01697735) The Therapeutic Effects of Statins and Berberine on the Hyperlipemia. U.S. National Institutes of Health.
Ref 525003ClinicalTrials.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 528257Identification of an immunogenic CD8+ T-cell epitope derived from gamma-globin, a putative tumor-associated antigen for juvenile myelomonocytic leukemia. Blood. 2006 Oct 15;108(8):2662-8. Epub 2006 Jun 15.
Ref 532941Dendritic cell-targeted vaccines--hope or hype. Nat Rev Immunol. 2014 Oct;14(10):705-11.
Ref 537114Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
Ref 548016Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021226)
Ref 549237Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034068)
Ref
Ref 526699Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull Exp Biol Med. 2003 Jun;135(6):590-2.
Ref 526935Telomerase-specific replication-selective virotherapy for human cancer. Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):285-92.
Ref 526963Vaccination of cancer patients against telomerase induces functional antitumor CD8+ T lymphocytes. Clin Cancer Res. 2004 Feb 1;10(3):828-39.
Ref 528486Telomerase 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. Epub 2006 Oct 24.
Ref 528698Telomerase immunity from bench to bedside: round one. J Transl Med. 2007 Feb 26;5:12.
Ref 530513In vitro activation of cytotoxic T-lymphocytes by hTERT-pulsed dendritic cells. J Immunotoxicol. 2009 Dec;6(4):243-8.
Ref 531368Targeting telomerase-expressing cancer cells. J Cell Mol Med. 2011 Jul;15(7):1433-42.
Ref 535389Stage specificity of Plasmodium falciparum telomerase and its inhibition by berberine. Parasitol Int. 2002 Mar;51(1):99-103.
Ref 535725Identification 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 535961Growth arrest, apoptosis, and telomere shortening of Barrett's-associated adenocarcinoma cells by a telomerase inhibitor. Gastroenterology. 2004 May;126(5):1337-46.
Ref 537114Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
Ref 1572591Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

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