Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTQY2EJ)

• DTT Name: TERT messenger RNA (TERT mRNA)
• Synonyms: Telomerase-associated protein 2 (mRNA); Telomerase catalytic subunit (mRNA); TRT (mRNA); TP2 (mRNA); TCS1 (mRNA); HEST2 (mRNA); EST2 (mRNA)
• Gene Name: TERT
• DTT Type: Successful target; [1]
• BioChemical Class: mRNA target
• UniProt ID: TERT_HUMAN
• TTD ID: T48945
• 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: 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. Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
• KEGG Pathway: HTLV-I infection (hsa05166)
• Reactome Pathway: Formation of the beta-catenin (R-HSA-201722)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[1]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[1]

52 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,3-bis(3,4-dihydroxyphenyl)prop-2-en-1-one	DMELSV1	Discovery agent	N.A.	Investigative	[2]
2,3-Dimethylnaphtho[2,3-f]quinoxaline-7,12-dione	DMKV9EZ	Discovery agent	N.A.	Investigative	[3]
2,7-Bis(3-chloropropionamido)anthraquinone	DMT9JHV	Discovery agent	N.A.	Investigative	[4]
2,7-Bis(4-chlorobutyramido)anthraquinone	DM8VWQ2	Discovery agent	N.A.	Investigative	[4]
2,7-Bis(acetamido)anthraquinone	DM2EPM4	Discovery agent	N.A.	Investigative	[4]
2,7-Bis(benzoamido)anthraquinone	DMEQC4X	Discovery agent	N.A.	Investigative	[4]
2,7-Bis(butyramido)anthraquinone	DM9S8LY	Discovery agent	N.A.	Investigative	[4]
2,7-Bis(chloroacetamido)anthraquinone	DM4MYAR	Discovery agent	N.A.	Investigative	[4]
2,7-Bis(cyclohexanecarbonamido)anthraquinone	DMTPZ8D	Discovery agent	N.A.	Investigative	[4]
2,7-Bis(cyclopentanecarbonamido)anthraquinone	DMP3EZ8	Discovery agent	N.A.	Investigative	[4]
2,7-Bis(cyclopropanecarbonamido)anthraquinone	DMY3V2B	Discovery agent	N.A.	Investigative	[4]
2,7-Bis(phenylacetamido)anthraquinone	DMEVIBT	Discovery agent	N.A.	Investigative	[4]
2,7-Bis(phenylpropionamido)anthraquinone	DMDKXEY	Discovery agent	N.A.	Investigative	[4]
2,7-Bis(propionamido)anthraquinone	DM2D1EJ	Discovery agent	N.A.	Investigative	[4]
2,7-Bis[2-(butylamino)acetamido]anthraquinone	DM3GTV0	Discovery agent	N.A.	Investigative	[4]
2,7-Bis[2-(diethylamino)acetamido]anthraquinone	DMKDSGE	Discovery agent	N.A.	Investigative	[4]
2,7-Bis[2-(dimethylamino)acetamido]anthraquinone	DMNW5PL	Discovery agent	N.A.	Investigative	[4]
2,7-Bis[2-(ethylamino)acetamido]anthraquinone	DMZ7EAC	Discovery agent	N.A.	Investigative	[4]
2,7-Bis[2-(isobutylamino)acetamido]anthraquinone	DMM4T1Q	Discovery agent	N.A.	Investigative	[4]
2,7-Bis[2-(isopropylamino)acetamido]anthraquinone	DMRQGWX	Discovery agent	N.A.	Investigative	[4]
2,7-Bis[2-(piperazino)acetamido]anthraquinone	DMPE8GX	Discovery agent	N.A.	Investigative	[4]
2,7-Bis[2-(piperidino)acetamido]anthraquinone	DMITF0P	Discovery agent	N.A.	Investigative	[4]
2,7-Bis[2-(propylamino)acetamido]anthraquinone	DMH89TO	Discovery agent	N.A.	Investigative	[4]
2,7-Bis[2-(pyrrolidino)acetamido]anthraquinone	DMHVKIJ	Discovery agent	N.A.	Investigative	[4]
2,7-Bis[3-(butylamino)propionamido]anthraquinone	DM4V63W	Discovery agent	N.A.	Investigative	[4]
2,7-Bis[3-(ethylamino)propionamido]anthraquinone	DMC537F	Discovery agent	N.A.	Investigative	[4]
2,7-Bis[3-(piperazino)propionamido]anthraquinone	DMOZEKQ	Discovery agent	N.A.	Investigative	[4]
2,7-Bis[3-(piperidino)propionamido]anthraquinone	DMET693	Discovery agent	N.A.	Investigative	[4]
2,7-Bis[3-(propylamino)propionamido]anthraquinone	DM6I90F	Discovery agent	N.A.	Investigative	[4]
2,7-Bis[3-(pyrrolidino)propionamido]anthraquinone	DMD6ZV5	Discovery agent	N.A.	Investigative	[4]
2,7-diaminoanthraquinone	DME0TZU	Discovery agent	N.A.	Investigative	[4]
2,7-Dinitroantraquinone	DMN56VM	Discovery agent	N.A.	Investigative	[4]
2-Butyl-1(3)H-anthra[1,2-d]imidazole-6,11-dione	DMY7RM8	Discovery agent	N.A.	Investigative	[3]
2-Heptyl-1(3)H-anthra[1,2-d]imidazole-6,11-dione	DMX45WE	Discovery agent	N.A.	Investigative	[3]
2-Methyl-1(3)H-anthrasimidazole-6,11-dione	DMKTQB2	Discovery agent	N.A.	Investigative	[3]
7,8,3',4'-tetrahydroxyflavone	DMOBEL9	Discovery agent	N.A.	Investigative	[2]
AURASPERONE A	DMDKH8N	Discovery agent	N.A.	Investigative	[5]
Cantide + Cisplatin	DM9IG2P	Tumour	2A00-2F9Z	Investigative	[1]
HOE-33258	DMKOMP2	Discovery agent	N.A.	Investigative	[6]
LIVIDOMYCIN A	DM6J1BY	Discovery agent	N.A.	Investigative	[6]
NSC-745794	DM1ETX5	Discovery agent	N.A.	Investigative	[3]
NSC-745795	DMI2GFM	Discovery agent	N.A.	Investigative	[3]
NSC-745796	DM8JMBI	Discovery agent	N.A.	Investigative	[3]
NSC-745797	DM9YAPX	Discovery agent	N.A.	Investigative	[3]
NSC-745798	DMSPQYV	Discovery agent	N.A.	Investigative	[3]
NSC-745799	DML6OMH	Discovery agent	N.A.	Investigative	[3]
NSC-745883	DMVA6R0	Discovery agent	N.A.	Investigative	[3]
NSC-745884	DM8W0J3	Discovery agent	N.A.	Investigative	[3]
NSC-745885	DMZQ803	Discovery agent	N.A.	Investigative	[3]
NSC-745886	DMHBYN5	Discovery agent	N.A.	Investigative	[3]
NSC-745887	DMG9BWY	Discovery agent	N.A.	Investigative	[3]
NSC-745888	DMWHYND	Discovery agent	N.A.	Investigative	[3]

References

• [1] Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.
• [2] Catecholic flavonoids acting as telomerase inhibitors. J Med Chem. 2004 Dec 16;47(26):6466-75.
• [3] Synthesis, cytotoxicity and human telomerase inhibition activities of a series of 1,2-heteroannelated anthraquinones and anthra[1,2-d]imidazole-6,1... Bioorg Med Chem. 2009 Nov 1;17(21):7418-28.
• [4] Synthesis, human telomerase inhibition and anti-proliferative studies of a series of 2,7-bis-substituted amido-anthraquinone derivatives. Bioorg Med Chem. 2008 Jul 15;16(14):6976-86.
• [5] New dimeric naphthopyrones from Aspergillus niger. J Nat Prod. 2003 Jan;66(1):136-9.
• [6] Nucleic acid-binding ligands identify new mechanisms to inhibit telomerase. Bioorg Med Chem Lett. 2004 Jul 5;14(13):3467-71.