Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTUJFD0)

• DTT Name: Telomerase reverse transcriptase (TERT)
• Synonyms: Telomerase-associated protein 2; Telomerase catalytic subunit; TRT; TP2; TCS1; HEST2; EST2
• Gene Name: TERT
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Kinase
• UniProt ID: TERT_HUMAN
• TTD ID: T86052
• 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
• 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.
• KEGG Pathway:
  Human papillomavirus infection (hsa05165)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Pathways in cancer (hsa05200)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
• Reactome Pathway: Formation of the beta-catenin (R-HSA-201722)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Berberine	DMC5Q8X	N. A.	N. A.	Phase 4	[1]

14 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GV1001	DMHULRK	Pancreatic cancer	2C10	Phase 3	[2]
Imetelstat	DMONWJ4	Myelodysplastic syndrome	2A37	Phase 2/3	[3]
VM1500A	DM9YSSY	Human immunodeficiency virus-1 infection	1C62	Phase 2/3	[4]
CB-10-01	DM2IFYZ	Melanoma	2C30	Phase 2	[5]
Dendritic cell vaccine	DML4PMG	Ovarian cancer	2C73	Phase 2	[6]
GRNVAC1	DMAHOEP	Acute myeloid leukaemia	2A60	Phase 2	[7]
Vx-001	DMDKWA3	Breast cancer	2C60-2C65	Phase 2	[8]
Epithalon	DMWSGZU	Ocular inflammation	9C61.24	Phase 1/2	[9]
OBP-301	DM9MF08	Breast cancer	2C60-2C65	Phase 1/2	[10]
AAV-hTERT	DMV1J21	Aging	MG2A	Phase 1	[11]
DC/I540/KLH vaccine	DM6K47B	Brain cancer	2A00	Phase 1	[12]
GRN163	DMGF71W	Multiple myeloma	2A83	Phase 1	[13]
KML-001	DM1D2O0	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]
TeloB-Vax	DMZG9U0	Prostate cancer	2C82.0	Phase 1	[15]

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2,3,7-trichloro-5-nitroquinoxaline (TNQX)	DMCKO6T	Discovery agent	N.A.	Investigative	[16]
PPA	DM86ZL2	Discovery agent	N.A.	Investigative	[17]
Telomestatin	DM6EIVM	Multiple myeloma	2A83	Investigative	[13]
TMPyP4	DMWO85H	Multiple myeloma	2A83	Investigative	[13]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Neuroectodermal tumour	2C82	Nervous tissue	8.59E-10	-0.08	-0.33
Ovarian cancer	2C82	Ovarian tissue	8.58E-01	-0.02	-0.07
Multiple myeloma	2C82	Bone marrow	7.34E-04	-0.44	-2.08

References

• [1] Stage specificity of Plasmodium falciparum telomerase and its inhibition by berberine. Parasitol Int. 2002 Mar;51(1):99-103.
• [2] 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.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Biochemical profiling of anti-HIV prodrug Elsulfavirine (Elpida(?)) and its active form VM1500A against a panel of twelve human carbonic anhydrase isoforms. J Enzyme Inhib Med Chem. 2021 Dec;36(1):1056-1060.
• [5] Telomerase immunity from bench to bedside: round one. J Transl Med. 2007 Feb 26;5:12.
• [6] In vitro activation of cytotoxic T-lymphocytes by hTERT-pulsed dendritic cells. J Immunotoxicol. 2009 Dec;6(4):243-8.
• [7] Targeting telomerase-expressing cancer cells. J Cell Mol Med. 2011 Jul;15(7):1433-42.
• [8] Clinical pipeline report, company report or official report of Vaxon-biotech.
• [9] Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull Exp Biol Med. 2003 Jun;135(6):590-2.
• [10] Telomerase-specific replication-selective virotherapy for human cancer. Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):285-92.
• [11] ClinicalTrials.gov (NCT04110964) Evaluation of Safety and Tolerability of Libella Gene Therapy (LGT) for Critical Limb Ischemia: AAV- hTERT. U.S.National Institutes of Health.
• [12] Vaccination of cancer patients against telomerase induces functional antitumor CD8+ T lymphocytes. Clin Cancer Res. 2004 Feb 1;10(3):828-39.
• [13] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [14] National Cancer Institute Drug Dictionary (drug id 672554).
• [15] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [16] 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.
• [17] Growth arrest, apoptosis, and telomere shortening of Barrett's-associated adenocarcinoma cells by a telomerase inhibitor. Gastroenterology. 2004 May;126(5):1337-46.