Page last updated: 2024-10-24
negative regulation of telomere maintenance via telomere lengthening
Definition
Target type: biologicalprocess
Any process that stops, prevents or reduces the frequency, rate or extent of telomere maintenance via telomere lengthening. [GO_REF:0000058, GOC:BHF, GOC:BHF_telomere, GOC:nc, GOC:TermGenie, PMID:23959892]
Negative regulation of telomere maintenance via telomere lengthening is a complex biological process that aims to prevent uncontrolled cell proliferation and maintain genomic stability. Telomeres are protective caps at the ends of chromosomes that shorten with each cell division. This shortening is a natural process that limits the number of times a cell can divide. However, in some cases, telomeres can be lengthened, which can contribute to uncontrolled cell growth and cancer. The negative regulation of telomere maintenance via telomere lengthening involves a variety of mechanisms that act to inhibit the lengthening of telomeres. These mechanisms include: 1) **Inhibition of telomerase activity:** Telomerase is an enzyme that adds DNA repeats to the ends of chromosomes, thereby lengthening telomeres. The activity of telomerase is tightly regulated in normal cells, but it can be upregulated in cancer cells. Negative regulation can involve downregulation of telomerase expression or inhibition of its enzymatic activity. 2) **Activation of telomere capping proteins:** Telomere capping proteins bind to the ends of chromosomes and protect them from degradation. These proteins also prevent telomere lengthening by inhibiting the access of telomerase to the telomere ends. 3) **Induction of DNA damage response pathways:** When telomeres become critically short, they can trigger DNA damage response pathways. These pathways can lead to cell cycle arrest or apoptosis, preventing further cell division and telomere lengthening. 4) **Regulation of telomere recombination:** Telomere recombination is a process that can lead to telomere lengthening. Negative regulation can involve the downregulation of factors that promote telomere recombination. 5) **Regulation of epigenetic modifications:** Epigenetic modifications, such as methylation, can influence the expression of genes involved in telomere maintenance. Negative regulation can involve the establishment of epigenetic modifications that suppress the expression of genes promoting telomere lengthening. These mechanisms work together to ensure that telomeres are maintained at appropriate lengths, preventing uncontrolled cell growth and preserving genomic stability. However, dysregulation of these mechanisms can contribute to cancer and other diseases.'
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Proteins (4)
| Protein | Definition | Taxonomy |
|---|---|---|
| Poly [ADP-ribose] polymerase tankyrase-2 | A poly [ADP-ribose] polymerase tankyrase-2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9H2K2] | Homo sapiens (human) |
| DNA repair endonuclease XPF | A DNA repair endonuclease XPF that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
| Poly [ADP-ribose] polymerase 1 | A poly [ADP-ribose] polymerase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P09874] | Homo sapiens (human) |
| Poly [ADP-ribose] polymerase tankyrase-1 | A poly [ADP-ribose] polymerase tankyrase-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O95271] | Homo sapiens (human) |
Compounds (78)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| niacinamide | nicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group. | pyridine alkaloid; pyridinecarboxamide; vitamin B3 | anti-inflammatory agent; antioxidant; cofactor; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor; EC 3.5.1.98 (histone deacetylase) inhibitor; Escherichia coli metabolite; geroprotector; human urinary metabolite; metabolite; mouse metabolite; neuroprotective agent; Saccharomyces cerevisiae metabolite; Sir2 inhibitor |
| 1,5-dihydroxyisoquinoline | 1,5-dihydroxyisoquinoline: structure in first source isoquinoline-1,5-diol : An isoquinolinol that is isoquinoline in which the hydrogens at positions 1 and 5 are replaced by hydroxy groups. | isoquinolinol | EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor |
| 3-aminobenzamide | benzamides; substituted aniline | EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor | |
| 4'-bromoflavone | 4'-bromoflavone: structure in first source | ||
| 4-amino-1,8-naphthalimide | 4-amino-1,8-naphthalimide: inhibits ADP-ribosylation; sometimes abreviated as 4-AN; | benzoisoquinoline; dicarboximide | |
| phenanthridone | phenanthridone : A member of the class of phenanthridines that is phenanthridine with an oxo substituent at position 6. A poly(ADP-ribose) polymerase (PARP) inhibitor, it has been shown to exhibit immunosuppressive activity. phenanthridone: coal tar derivative; structure given in first source | lactam; phenanthridines | EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor; immunosuppressive agent; mutagen |
| 5-aminoisoquinolinone | 5-aminoisoquinolinone: structure in first source | isoquinolines | |
| benzamide | benzamide : An aromatic amide that consists of benzene bearing a single carboxamido substituent. The parent of the class of benzamides. | benzamides | |
| pj-34 | PJ34 : A member of the class of phenanthridines that is 5,6-dihydrophenanthridine substituted at positions 2 and 6 by (N,N-dimethylglycyl)amino and oxo groups, respectively. It is a potent inhibitor of poly(ADP-ribose) polymerases PARP1 and PARP2 (IC50 of 110 nM and 86 nM, respectively) and exhibits anti-cancer, cardioprotective and neuroprotective properties. | phenanthridines; secondary carboxamide; tertiary amino compound | angiogenesis inhibitor; anti-inflammatory agent; antiatherosclerotic agent; antineoplastic agent; apoptosis inducer; cardioprotective agent; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor; neuroprotective agent |
| carbostyril | quinolin-2(1H)-one : A quinolone that is 1,2-dihydroquinoline substituted by an oxo group at position 2. Quinolones: A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID. | monohydroxyquinoline; quinolone | bacterial xenobiotic metabolite |
| 1-hydroxyphthalazine | 1-hydroxyphthalazine: RN given refers to cpd with unspecified locants; do not confuse with cpd phthalazinol RN: 56611-65-5 | phthalazines | |
| chlorthenoxazin | chlorthenoxazin: RN given refers to parent cpd; structure | benzoxazine | |
| isocarbostyril | isoquinolinone : An isoquinoline containing one or more oxo groups. | isoquinolines | |
| flavone | flavone : The simplest member of the class of flavones that consists of 4H-chromen-4-one bearing a phenyl substituent at position 2. flavone: RN given refers to unlabeled cpd; structure given in first source | flavones | metabolite; nematicide |
| 2,4(1h,3h)-quinazolinedione | 2,4(1H,3H)-quinazolinedione: structure given in first source | ||
| 4-hydroxybenzamide | |||
| naphthalimides | Naphthalimides: Compounds with three fused rings that appear like a naphthalene fused to piperidone or like a benz(de)isoquinoline-1,3-dione (not to be confused with BENZYLISOQUINOLINES which have a methyl separating the naphthyl from the benzyl rings). Members are CYTOTOXINS. | ||
| 4-methylquinolin-2(1H)-one | 4-methylquinolin-2(1H)-one : A quinolone that is quinolin-2(1H)-one substituted by a methyl group at position 4. | quinolone | |
| 4-fluorobenzamide | 4-fluorobenzamide: structure in first source | ||
| 5-iodo-6-amino-1,2-benzopyrone | |||
| alantolactone | alantolactone : A sesquiterpene lactone that is 3a,5,6,7,8,8a,9,9a-octahydronaphtho[2,3-b]furan-2-one bearing two methyl substituents at positions 5 and 8a as well as a methylidene substituent at position 3. alantolactone: allergenic sesquiterpene lactone; crystalline mixture of alantolactones from group of sesquiterpenes; structure | naphthofuran; olefinic compound; sesquiterpene lactone | antineoplastic agent; apoptosis inducer; plant metabolite |
| 4-aminobenzamide | benzamides | ||
| 4-Methoxybenzamide | benzamides | ||
| 4'-methoxyflavone | 4'-methoxyflavone: from seeds of Psoralea corylifolia (Fabaceae); structure in first source | ether; flavonoids | |
| n-hydroxynaphthalimide | N-hydroxynaphthalimide: structure in first source | ||
| 3-methoxybenzamide | |||
| lestaurtinib | indolocarbazole | ||
| 3',4'-dihydroxyflavone | 3',4'-dihydroxyflavone: inhibitors of arachidonic acid peroxidation | ||
| 3-methoxyflavone | 3-methoxyflavone: from Aspergillus niger; structure in first source | ||
| 2'-methoxyflavone | ether; flavonoids | ||
| 6-methoxyflavone | 6-methoxyflavone: suppresses NFAT-mediated T cell activation; structure in first source | ether; flavonoids | |
| 3,4-dihydro-5-methyl-1(2h)-isoquinolinone | 3,4-dihydro-5-methyl-1(2H)-isoquinolinone: structure given in first source | isoquinolines | |
| 1-oxo-1,2,3,4-tetrahydroisoquinoline | 1-oxo-1,2,3,4-tetrahydroisoquinoline: structure given in first source | ||
| 4'-chloroflavone | 4'-chloroflavone: structure given in first source | ||
| cyclo(alanylalanyl) | |||
| sorafenib | (trifluoromethyl)benzenes; aromatic ether; monochlorobenzenes; phenylureas; pyridinecarboxamide | angiogenesis inhibitor; anticoronaviral agent; antineoplastic agent; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; ferroptosis inducer; tyrosine kinase inhibitor | |
| 3-hydroxy-quinazoline-2,4-dione | 3-hydroxy-quinazoline-2,4-dione: structure in first source | ||
| 4'-hydroxyflavone | 4'-hydroxyflavone: structure in first source | ||
| 6-chloroflavone | 6-chloroflavone: structure in first source | ||
| e-z cinnamic acid | cinnamic acid : A monocarboxylic acid that consists of acrylic acid bearing a phenyl substituent at the 3-position. It is found in Cinnamomum cassia. trans-cinnamic acid : The E (trans) isomer of cinnamic acid | cinnamic acid | plant metabolite |
| 7-methoxyflavone | 7-methoxyflavone: an aromatase inhibitor | ether; flavonoids | |
| 6-methylflavone | 6-methylflavone: structure in first source | ||
| N-(3-methylphenyl)-4-tetrazolo[1,5-a]quinoxalinamine | quinoxaline derivative | ||
| iwr-1 exo | IWR-1-exo : A dicarboximide having an exo bridged phthalimide structure, substituted at nitrogen by a 4-(quinolin-8-ylcarbamoyl)benzoyl group. It is a weak axin stabilizer, an analogue of IWR-1-endo. | bridged compound; dicarboximide | axin stabilizer |
| N-[4-[[[4-(4-methoxyphenyl)-4-oxanyl]methylamino]-oxomethyl]phenyl]-2-furancarboxamide | aromatic amide; furans | ||
| tandutinib | aromatic ether; N-arylpiperazine; N-carbamoylpiperazine; phenylureas; piperidines; quinazolines; tertiary amino compound | antineoplastic agent; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor | |
| ha 1100 | HA 1100: intracellular calcium antagonist | ||
| apigenin | Chamomile: Common name for several daisy-like plants (MATRICARIA; TRIPLEUROSPERMUM; ANTHEMIS; CHAMAEMELUM) native to Europe and Western Asia, now naturalized in the United States and Australia. | trihydroxyflavone | antineoplastic agent; metabolite |
| luteolin | 3'-hydroxyflavonoid; tetrahydroxyflavone | angiogenesis inhibitor; anti-inflammatory agent; antineoplastic agent; apoptosis inducer; c-Jun N-terminal kinase inhibitor; EC 2.3.1.85 (fatty acid synthase) inhibitor; immunomodulator; nephroprotective agent; plant metabolite; radical scavenger; vascular endothelial growth factor receptor antagonist | |
| amentoflavone | biflavonoid; hydroxyflavone; ring assembly | angiogenesis inhibitor; antiviral agent; cathepsin B inhibitor; P450 inhibitor; plant metabolite | |
| 3',4',7-trihydroxyflavone | 3',4',7-trihydroxyflavone: from the Sudanese medicinal plant Albizia zygia; structure in first source | flavones | |
| su 11248 | monocarboxylic acid amide; pyrroles | angiogenesis inhibitor; antineoplastic agent; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor; immunomodulator; neuroprotective agent; vascular endothelial growth factor receptor antagonist | |
| adenosine diphosphate (hydroxymethyl)pyrrolidinediol | dihydroxypyrrolidine; purine ribonucleoside 5'-diphosphate | ||
| midostaurin | midostaurin : An organic heterooctacyclic compound that is the N-benzoyl derivative of staurosporine. | benzamides; gamma-lactam; indolocarbazole; organic heterooctacyclic compound | antineoplastic agent; EC 2.7.11.13 (protein kinase C) inhibitor |
| ag 14361 | benzimidazoles | ||
| gpi 6150 | |||
| rucaparib | AG14447: Poly(ADP-ribose) polymerase inhibitor; structure in first source | azepinoindole; caprolactams; organofluorine compound; secondary amino compound | antineoplastic agent; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor |
| 3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2h)-isoquinolinone | |||
| veliparib | benzimidazoles | EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor | |
| N-(4-methylphenyl)-4-tetrazolo[1,5-a]quinoxalinamine | quinoxaline derivative | ||
| olaparib | cyclopropanes; monofluorobenzenes; N-acylpiperazine; phthalazines | antineoplastic agent; apoptosis inducer; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor | |
| quizartinib | benzoimidazothiazole; isoxazoles; morpholines; phenylureas | antineoplastic agent; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor; necroptosis inhibitor | |
| niraparib | 2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamide : A member of the class of indazoles that is 2H-indazole substituted by 4-(piperidin-3-yl)phenyl and aminocarbonyl groups at positions 2 and 7, respectively. It is a potent PARP1 inhibitor with IC50 of 3.2 nM. | benzenes; indazoles; piperidines; primary carboxamide | antineoplastic agent; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor |
| niraparib | niraparib : A 2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamide that has S-configuration. It is a potent inhibitor of PARP1 and PARP2 (IC50 of 3.8 and 2.1 nM, respectively) and approved as a first-line maintenance treatment for women with advanced ovarian cancer after responding to platinum-based chemotherapy. niraparib: structure in first source | 2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamide | antineoplastic agent; apoptosis inducer; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor; radiosensitizing agent |
| cep 26401 | pyridazines; ring assembly | ||
| iwr-1 endo | IWR-1-endo : A dicarboximide having an endo bridged phthalimide structure, substituted at nitrogen by a 4-(quinolin-8-ylcarbamoyl)benzoyl group. | benzamides; bridged compound; dicarboximide; quinolines | axin stabilizer; Wnt signalling inhibitor |
| nms-p118 | NMS-P118: a PARP-1 inhibitor; structure in first source | ||
| g007-lk | G007-LK: potent and specific small-molecule tankyrase inhibitor; structure in first source | ||
| CCT251545 | CCT251545 : A chloropyridine that is 3-chloropyridine substituted by a 1-oxo-2,8-diazaspiro[4.5]decan-8-yl group and a 4-(1-methyl-1H-pyrazol-4-yl)phenyl group at positions 4 and 5, respectively. It is an orally bioavailable inhibitor of Wnt signaling (IC50 = 5 nM) and a potent and selective chemical probe for cyclin-dependent kinases CDK8 and CDK19. CCT251545: a Wnt signaling inhibitor; structure in first source | azaspiro compound; chloropyridine; pyrazoles | antineoplastic agent; EC 2.7.11.22 (cyclin-dependent kinase) inhibitor; Wnt signalling inhibitor |
| nu 1025 | NU 1064: structure in first source | phenols; quinazolines | EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor |
| 2-methyl-4(3h)-quinazolinone | 2-methyl-4(3H)-quinazolinone: from Bacillus cereus; structure given in first source | ||
| 4-hydroxyquinazoline | 4-oxo-3,4-dihydroquinazoline: structure in first source | quinazolines | |
| 1,4-Dihydrothieno[3,2-d]pyrimidin-4-one | organic heterobicyclic compound; organonitrogen heterocyclic compound; organosulfur heterocyclic compound | ||
| xav939 | XAV939 : A thiopyranopyrimidine in which a 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine skeleton is substituted at C-4 by a hydroxy group and at C-2 by a para-(trifluoromethyl)phenyl group. XAV939: selectively inhibits beta-catenin-mediated transcription; structure in first source | (trifluoromethyl)benzenes; thiopyranopyrimidine | tankyrase inhibitor |
| 2-(4-methoxyphenyl)-1H-quinazolin-4-one | quinazolines | ||
| bmn 673 | talazoparib: inhibits both PARP1 and PARP2; structure in first source | ||
| me0328 | ME0328: inhibits ARTD3; structure in first source | ||
| nvp-tnks656 |