Target Information
| Target General Information | Top | |||||
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| Target ID |
T88304
(Former ID: TTDNC00597)
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| Target Name |
DNA [cytosine-5]-methyltransferase 1 (DNMT1)
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| Synonyms |
MCMT; M.HsaI; Dnmt1; DNMT; DNA methyltransferase HsaI; DNA MTase HsaI; DNA (cytosine5)methyltransferase 1; DNA (cytosine-5)-methyltransferase 1; CXXCtype zinc finger protein 9; CXXC9; CXXC-type zinc finger protein 9; AIM
Click to Show/Hide
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| Gene Name |
DNMT1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Acute myeloid leukaemia [ICD-11: 2A60] | |||||
| 2 | Myelodysplastic syndrome [ICD-11: 2A37] | |||||
| 3 | Myeloproliferative neoplasm [ICD-11: 2A20] | |||||
| Function |
Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells. Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. Promotes tumor growth. Methylates CpG residues.
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| BioChemical Class |
Methyltransferase
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| UniProt ID | ||||||
| EC Number |
EC 2.1.1.37
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| Sequence |
MPARTAPARVPTLAVPAISLPDDVRRRLKDLERDSLTEKECVKEKLNLLHEFLQTEIKNQ
LCDLETKLRKEELSEEGYLAKVKSLLNKDLSLENGAHAYNREVNGRLENGNQARSEARRV GMADANSPPKPLSKPRTPRRSKSDGEAKPEPSPSPRITRKSTRQTTITSHFAKGPAKRKP QEESERAKSDESIKEEDKDQDEKRRRVTSRERVARPLPAEEPERAKSGTRTEKEEERDEK EEKRLRSQTKEPTPKQKLKEEPDREARAGVQADEDEDGDEKDEKKHRSQPKDLAAKRRPE EKEPEKVNPQISDEKDEDEKEEKRRKTTPKEPTEKKMARAKTVMNSKTHPPKCIQCGQYL DDPDLKYGQHPPDAVDEPQMLTNEKLSIFDANESGFESYEALPQHKLTCFSVYCKHGHLC PIDTGLIEKNIELFFSGSAKPIYDDDPSLEGGVNGKNLGPINEWWITGFDGGEKALIGFS TSFAEYILMDPSPEYAPIFGLMQEKIYISKIVVEFLQSNSDSTYEDLINKIETTVPPSGL NLNRFTEDSLLRHAQFVVEQVESYDEAGDSDEQPIFLTPCMRDLIKLAGVTLGQRRAQAR RQTIRHSTREKDRGPTKATTTKLVYQIFDTFFAEQIEKDDREDKENAFKRRRCGVCEVCQ QPECGKCKACKDMVKFGGSGRSKQACQERRCPNMAMKEADDDEEVDDNIPEMPSPKKMHQ GKKKKQNKNRISWVGEAVKTDGKKSYYKKVCIDAETLEVGDCVSVIPDDSSKPLYLARVT ALWEDSSNGQMFHAHWFCAGTDTVLGATSDPLELFLVDECEDMQLSYIHSKVKVIYKAPS ENWAMEGGMDPESLLEGDDGKTYFYQLWYDQDYARFESPPKTQPTEDNKFKFCVSCARLA EMRQKEIPRVLEQLEDLDSRVLYYSATKNGILYRVGDGVYLPPEAFTFNIKLSSPVKRPR KEPVDEDLYPEHYRKYSDYIKGSNLDAPEPYRIGRIKEIFCPKKSNGRPNETDIKIRVNK FYRPENTHKSTPASYHADINLLYWSDEEAVVDFKAVQGRCTVEYGEDLPECVQVYSMGGP NRFYFLEAYNAKSKSFEDPPNHARSPGNKGKGKGKGKGKPKSQACEPSEPEIEIKLPKLR TLDVFSGCGGLSEGFHQAGISDTLWAIEMWDPAAQAFRLNNPGSTVFTEDCNILLKLVMA GETTNSRGQRLPQKGDVEMLCGGPPCQGFSGMNRFNSRTYSKFKNSLVVSFLSYCDYYRP RFFLLENVRNFVSFKRSMVLKLTLRCLVRMGYQCTFGVLQAGQYGVAQTRRRAIILAAAP GEKLPLFPEPLHVFAPRACQLSVVVDDKKFVSNITRLSSGPFRTITVRDTMSDLPEVRNG ASALEISYNGEPQSWFQRQLRGAQYQPILRDHICKDMSALVAARMRHIPLAPGSDWRDLP NIEVRLSDGTMARKLRYTHHDRKNGRSSSGALRGVCSCVEAGKACDPAARQFNTLIPWCL PHTGNRHNHWAGLYGRLEWDGFFSTTVTNPEPMGKQGRVLHPEQHRVVSVRECARSQGFP DTYRLFGNILDKHRQVGNAVPPPLAKAIGLEIKLCMLAKARESASAKIKEEEAAKD Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| ADReCS ID | BADD_A02700 | |||||
| HIT2.0 ID | T27LA6 | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 8 Clinical Trial Drugs | + | ||||
| 1 | CC-486 | Drug Info | Phase 3 | Myelodysplastic syndrome | [2] | |
| 2 | Guadecitabine | Drug Info | Phase 3 | Myelodysplastic syndrome | [3] | |
| 3 | S-110 | Drug Info | Phase 3 | Acute myeloid leukaemia | [3], [4] | |
| 4 | SGI110 | Drug Info | Phase 3 | Acute myeloid leukaemia | [4] | |
| 5 | Antroquinonol | Drug Info | Phase 2 | Non-small-cell lung cancer | [5] | |
| 6 | Palifosfamide | Drug Info | Phase 2 | Soft tissue sarcoma | [6] | |
| 7 | RX-3117 | Drug Info | Phase 2 | Bladder cancer | [3] | |
| 8 | GSK4172239 | Drug Info | Phase 1 | Sickle-cell disorder | [7] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 25 Inhibitor drugs | + | ||||
| 1 | CC-486 | Drug Info | [8] | |||
| 2 | Guadecitabine | Drug Info | [3] | |||
| 3 | S-110 | Drug Info | [1] | |||
| 4 | Antroquinonol | Drug Info | [10] | |||
| 5 | Palifosfamide | Drug Info | [11] | |||
| 6 | RX-3117 | Drug Info | [12] | |||
| 7 | GSK4172239 | Drug Info | [13] | |||
| 8 | PMID27376512-Compound-asCEBP-1 | Drug Info | [14] | |||
| 9 | PMID27376512-Compound-asCEBP-1HPE | Drug Info | [14] | |||
| 10 | PMID27376512-Compound-asCEBP-2 | Drug Info | [14] | |||
| 11 | PMID27376512-Compound-asCEBP-2HPE | Drug Info | [14] | |||
| 12 | PMID27376512-Compound-miR-155-5p | Drug Info | [14] | |||
| 13 | PMID27376512-Compound-MTC-422 | Drug Info | [14] | |||
| 14 | PMID27376512-Compound-MTC-423 | Drug Info | [14] | |||
| 15 | PMID27376512-Compound-MTC-424 | Drug Info | [14] | |||
| 16 | PMID27376512-Compound-MTC-427 | Drug Info | [14] | |||
| 17 | PMID27376512-Compound-MTC-433 | Drug Info | [14] | |||
| 18 | PMID27376512-Compound-Table1Example11 | Drug Info | [14] | |||
| 19 | PMID27376512-Compound-Table1Example16 | Drug Info | [14] | |||
| 20 | PMID27376512-Compound-Table1Example30 | Drug Info | [14] | |||
| 21 | PMID27376512-Compound-Table1Example4 | Drug Info | [14] | |||
| 22 | PMID27376512-Compound-Table1Example5 | Drug Info | [14] | |||
| 23 | PMID27376512-Compound-Table1Example8 | Drug Info | [14] | |||
| 24 | CP-4200 | Drug Info | [15] | |||
| 25 | XB-05 | Drug Info | [15] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | SGI110 | Drug Info | [9] | |||
| 2 | PMX-700 | Drug Info | [15] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Ademetionine | Ligand Info | |||||
| Structure Description | Human DNMT1(729-1600) Bound to Zebularine-Containing 12mer dsDNA and Cofactor SAM | PDB:7SFG | ||||
| Method | X-ray diffraction | Resolution | 2.43 Å | Mutation | No | [16] |
| PDB Sequence |
RISWVGEAVK
739 TDGKKSYYKK749 VCIDAETLEV759 GDCVSVIPDD769 SSKPLYLARV779 TALWEDSSNG 789 QMFHAHWFCA799 GTDTVLGATS809 DPLELFLVDE819 CEDMQLSYIH829 SKVKVIYKAP 839 SENWAMEGGM849 DKTYFYQLWY869 DQDYARFESP879 PKTQPNKFKF892 CVSCARLAEM 902 RQKEIPRVLE912 QLEDLDSRVL922 YYSATKNGIL932 YRVGDGVYLP942 PEAFTFNIKP 963 VDEDLYPEHY973 RKYSDYIKGS983 NLDAPEPYRI993 GRIKEIFCPK1003 KSNGRPNETD 1013 IKIRVNKFYR1023 PENTHKSTPA1033 SYHADINLLY1043 WSDEEAVVDF1053 KAVQGRCTVE 1063 YGEDLPECVQ1073 VYSMGGPNRF1083 YFLEAYNAKS1093 KSFEDPPNHA1103 RKLPKLRTLD 1143 VFSGCGGLSE1153 GFHQAGISDT1163 LWAIEMWDPA1173 AQAFRLNNPG1183 STVFTEDCNI 1193 LLKLVMAGET1203 TNSRGQRLPQ1213 KGDVEMLCGG1223 PPCQGFSGMN1233 RFNSRTYSKF 1243 KNSLVVSFLS1253 YCDYYRPRFF1263 LLENVRNFVS1273 FKRSMVLKLT1283 LRCLVRMGYQ 1293 CTFGVLQAGQ1303 YGVAQTRRRA1313 IILAAAPGEK1323 LPLFPEPLHV1333 FAPRACQLSV 1343 VVDDKKFVSN1353 ITRLSSGPFR1363 TITVRDTMSD1373 LPEVRNGASA1383 LEISYNGEPQ 1393 SWFQRQLRGA1403 QYQPILRDHI1413 CKDMSALVAA1423 RMRHIPLAPG1433 SDWRDLPNIE 1443 VRLSDGTMAR1453 KLRYTHHDRK1463 NGRSSSGALR1473 GVCSCVEAGK1483 ACDPAARQFN 1493 TLIPWCLPHT1503 GNRHNHWAGL1513 YGRLEWDGFF1523 STTVTNPEPM1533 GKQGRVLHPE 1543 QHRVVSVREC1553 ARSQGFPDTY1563 RLFGNILDKH1573 RQVGNAVPPP1583 LAKAIGLEIK 1593 LCMLAKA
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PHE1145
3.160
SER1146
3.056
GLY1147
3.560
CYS1148
3.791
GLY1149
3.410
GLY1150
3.107
LEU1151
3.034
ILE1167
4.102
GLU1168
2.590
MET1169
3.333
TRP1170
3.144
ALA1173
4.504
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| Ligand Name: Sinefungin | Ligand Info | |||||
| Structure Description | Structure of human DNMT1 (601-1600) in complex with Sinefungin | PDB:3SWR | ||||
| Method | X-ray diffraction | Resolution | 2.49 Å | Mutation | No | [17] |
| PDB Sequence |
RQTIRHSTRE
610 PTKATTTKLV624 YQIFDTFFAE634 QINAFKRRRC653 GVCEVCQQPE663 CGKCKACKDM 673 VKFGGSGRSK683 QACQERRCPN693 MAMKEADDDE703 EVDDNIPEMP713 SPKKMHQGKK 723 KKQNKNRISW733 VGEAVKTDGK743 KSYYKKVCID753 AETLEVGDCV763 SVIPDDSSKP 773 LYLARVTALW783 EDSSNGQMFH793 AHWFCAGTDT803 VLGATSDPLE813 LFLVDECEDM 823 QLSYIHSKVK833 VIYKAPSENW843 AMEGGMDPES853 LLEGDDGKTY863 FYQLWYDQDY 873 ARFESPPKTQ883 PTEDNKFKFC893 VSCARLAEMR903 QKEIPRVLEQ913 LEDLDSRVLY 923 YSATKNGILY933 RVGDGVYLPP943 EAFTFNIKLS953 SPVKRPRKEP963 VDEDLYPEHY 973 RKYSDYIKGS983 NLDAPEPYRI993 GRIKEIFCPK1003 KSNGRPNETD1013 IKIRVNKFYR 1023 PENTHKSTPA1033 SYHADINLLY1043 WSDEEAVVDF1053 KAVQGRCTVE1063 YGEDLPECVQ 1073 VYSMGGPNRF1083 YFLEAYNAKS1093 KSFEDPPNHA1103 RSPEPEIEIK1135 LPKLRTLDVF 1145 SGCGGLSEGF1155 HQAGISDTLW1165 AIEMWDPAAQ1175 AFRLNNPGST1185 VFTEDCNILL 1195 KLVMAGETTN1205 SRGQRLPQKG1215 DVEMLCGGPP1225 CQGFSGMNRF1235 NSRTYSKFKN 1245 SLVVSFLSYC1255 DYYRPRFFLL1265 ENVRNFVSFK1275 RSMVLKLTLR1285 CLVRMGYQCT 1295 FGVLQAGQYG1305 VAQTRRRAII1315 LAAAPGEKLP1325 LFPEPLHVFA1335 PRACQLSVVV 1345 DDKKFVSNIT1355 RLSSGPFRTI1365 TVRDTMSDLP1375 EVRNGASALE1385 ISYNGEPQSW 1395 FQRQLRGAQY1405 QPILRDHICK1415 DMSALVAARM1425 RHIPLAPGSD1435 WRDLPNIEVR 1445 LSDGTMARKL1455 RYTHHDRKNG1465 RSSSGALRGV1475 CSCVEAGKAC1485 DPAARQFNTL 1495 IPWCLPHTGN1505 RHNHWAGLYG1515 RLEWDGFFST1525 TVTNPEPMGK1535 QGRVLHPEQH 1545 RVVSVRECAR1555 SQGFPDTYRL1565 FGNILDKHRQ1575 VGNAVPPPLA1585 KAIGLEIKLC 1595 MLAKA
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PHE1145
3.407
SER1146
3.138
GLY1147
3.412
CYS1148
3.754
GLY1149
3.468
GLY1150
3.363
LEU1151
2.870
ILE1167
4.020
GLU1168
2.693
MET1169
3.212
TRP1170
3.280
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Cysteine and methionine metabolism | hsa00270 | Affiliated Target |
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| Class: Metabolism => Amino acid metabolism | Pathway Hierarchy | ||
| Degree | 27 | Degree centrality | 2.90E-03 | Betweenness centrality | 3.05E-03 |
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| Closeness centrality | 2.53E-01 | Radiality | 1.44E+01 | Clustering coefficient | 1.97E-01 |
| Neighborhood connectivity | 5.05E+01 | Topological coefficient | 6.40E-02 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| 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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| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Cysteine and methionine metabolism | |||||
| 2 | Metabolic pathways | |||||
| 3 | MicroRNAs in cancer | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Methionine Metabolism | |||||
| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | Regulation of retinoblastoma protein | |||||
| Reactome | [+] 3 Reactome Pathways | + | ||||
| 1 | PRC2 methylates histones and DNA | |||||
| 2 | NoRC negatively regulates rRNA expression | |||||
| 3 | DNA methylation | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | Trans-sulfuration and one carbon metabolism | |||||
| 2 | Retinoblastoma (RB) in Cancer | |||||
| 3 | One Carbon Metabolism | |||||
| 4 | Trans-sulfuration pathway | |||||
| References | Top | |||||
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| REF 1 | S110, a 5-Aza-2'-deoxycytidine-containing dinucleotide, is an effective DNA methylation inhibitor in vivo and can reduce tumor growth. Mol Cancer Ther. 2010 May;9(5):1443-50. | |||||
| REF 2 | J Clin Oncol 33, 2015 (suppl, abstr TPS7097). | |||||
| REF 3 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 4 | ClinicalTrials.gov (NCT02348489) SGI-110 in Adults With Untreated Acute Myeloid Leukemia (AML), Not Considered Candidates for Intensive Remission Induction. U.S. National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT02047344) Efficacy, Safety and Pharmacokinetics Study of Antroquinonol to Treat NSCLC. U.S. National Institutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT01808534) Palifosfamide in Treating Patients With Recurrent Germ Cell Tumors. U.S. National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.gov (NCT05660265) A Randomized, Placebo-controlled, Double-Blind (Sponsor Unblind), Parallel Group, Single Dose, Dose Escalation Phase I Study in Sickle Cell Disease Participants, to Evaluate the Safety, Tolerability, and Pharmacokinetics of GSK4172239D. U.S.National Institutes of Health. | |||||
| REF 8 | Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes. Leukemia. 2016 Apr;30(4):889-96. | |||||
| REF 9 | Immunomodulatory action of the DNA methyltransferase inhibitor SGI-110 in epithelial ovarian cancer cells and xenografts. Epigenetics. 2015;10(3):237-46. | |||||
| REF 10 | Antroquinonol D, isolated from Antrodia camphorata, with DNA demethylation and anticancer potential. J Agric Food Chem. 2014 Jun 18;62(24):5625-35. | |||||
| REF 11 | Anticancer activity of stabilized palifosfamide in vivo: schedule effects, oral bioavailability, and enhanced activity with docetaxel and doxorubicin. Anticancer Drugs. 2012 Feb;23(2):173-84. | |||||
| REF 12 | Metabolism, mechanism of action and sensitivity profile of fluorocyclopentenylcytosine (RX-3117; TV-1360). Invest New Drugs. 2013 Dec;31(6):1444-57. | |||||
| REF 13 | Clinical pipeline report, company report or official report of GlaxoSmithKline | |||||
| REF 14 | DNA methyltransferase inhibitors: an updated patent review (2012-2015).Expert Opin Ther Pat. 2016 Sep;26(9):1017-30. | |||||
| REF 15 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2605). | |||||
| REF 16 | Structural characterization of dicyanopyridine containing DNMT1-selective, non-nucleoside inhibitors. Structure. 2022 Jun 2;30(6):793-802.e5. | |||||
| REF 17 | Structure of human DNMT1 (residues 600-1600) in complex with Sinefungin | |||||
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