m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00625
 [1], [2], [3], [4]
m6A modification MIR126 MIR126 METTL14 Methylation : m6A sites Indirect Enhancement RNA modification VEGFA VEGFA ALKBH3 Demethylation : modification sites
m6A Modification:
m6A Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
m6A Target microRNA 126 (MIR126)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type RNA modification (RNAMod)  >> N1-methyladenosine (m1A)
Epigenetic Regulator Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 (ALKBH3) ERASER View Details
Regulated Target Vascular endothelial growth factor A (VEGFA) View Details
Crosstalk Relationship m6A  →  m1A Enhancement
Crosstalk Mechanism m6A modification indirectly impacts RNA modification through downstream signaling pathways
Crosstalk Summary METTL14 interacts with microRNA 126 (MIR126), decreasing its m6A level and promoting its physical interaction with Vascular endothelial growth factor A (VEGFA), which was regulated by ALKBH3-mediated m1A modification.
In-vitro Model
 MIA PaCa-2 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0428
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
KU-7 Human papillomavirus-related cervical adenocarcinoma Homo sapiens CVCL_4714
Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens CVCL_0326
SMMC-7721 Endocervical adenocarcinoma Homo sapiens CVCL_0534
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Vascular endothelial growth factor A (VEGFA) 85 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Ranibizumab Approved [5]
Synonyms
Ranibizumab (nasal spray, hereditary hemorrhagic telangiectasia)
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External Link
TTD: D04EYG
 Compound Name Bevacizumab Approved [6]
Synonyms
Bevacizumab (ophthalmic slow-release tissue tablet)
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MOA Inhibitor
External Link
TTD: D04KBL
 Compound Name Brolucizumab Approved [7]
MOA Inhibitor
External Link
TTD: D5DO9L
 Compound Name Faricimab Approved [8]
Synonyms
RO6867461; RG7716
    Click to Show/Hide
External Link
TTD: D9MWL4
 Compound Name Aflibercept Approved [9]
Synonyms
Ziv-Aflibercept; Zaltrap (TN); VEGF Trap; VEGF Trap-Eye
    Click to Show/Hide
MOA Modulator
External Link
TTD: D0C9ET
 Compound Name Bevacizumab + Rituximab Phase 3 [10]
MOA Inhibitor
External Link
CID: 24801580
TTD: D08CGU
 Compound Name Bevacizumab + Erlotinib Phase 3 [10]
MOA Inhibitor
External Link
TTD: D09BKY
 Compound Name Bevacizumab + Trastuzumab Phase 3 [10]
Synonyms
Lithocholic acid; 434-13-9; Lithocolic acid; Lithocholate; 3alpha-Hydroxy-5beta-cholanic acid; 3alpha-Hydroxy-5beta-cholan-24-oic acid; 3-Hydroxycholan-24-oic acid; 3alpha-Hydroxycholanic acid; 3-alpha-Hydroxycholanic acid; 5beta-Cholanic acid-3alpha-ol; NCI-C03861; 3alpha-Hydroxy-5beta-cholanoic acid; (3alpha,5beta)-3-hydroxycholan-24-oic acid; 3-alpha-Hydroxy-5-beta-cholanic acid; CCRIS 363; UNII-5QU0I8393U; 3alpha-Hydroxy-5beta-cholanate; 5-beta-Cholanic acid, 3-alpha-hydroxy-; Cholan-24-oic acid, 3-hydroxy-,
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 9903
TTD: D04SLF
 Compound Name Avastin+/-Tarceva Phase 3 [11]
Synonyms
Juglone; 481-39-0; 5-Hydroxy-1,4-naphthoquinone; 5-Hydroxy-1,4-naphthalenedione; Regianin; Juglon; Nucin; 5-Hydroxynaphthalene-1,4-dione; Walnut extract; 5-Hydroxynaphthoquinone; Akhnot; Yuglon; 8-Hydroxy-1,4-naphthoquinone; CI Natural Brown 7; 1,4-NAPHTHALENEDIONE, 5-HYDROXY-; 5-Hydroxy-p-naphthoquinone; 1,4-Naphthoquinone, 5-hydroxy-; CI 75500; Juglane; Jugnlon; Iuglon; Caswell No 515AA; 1,4-Naphthoquinone, 8-hydroxy-; 5-Hydroxy-1,4-naphthosemiquinone; 5-Hydroxy-1,4-naftochinon; UNII-W6Q80SK9L6; NSC 622948; NSC 153189; CCRIS
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 3806
TTD: D0C0NH
 Compound Name Abicipar pegol Phase 2 [12]
MOA Inhibitor
External Link
TTD: D0CJ7Z
 Compound Name PTC299 Phase 2 [13]
Synonyms
6-(4-Fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole; skf-86002; 72873-74-6; Skf 86002; F 86002; F 86002-A(2); UNII-9R6QDF1UO7; 9R6QDF1UO7; CHEMBL313417; 5-(4-Pyridyl)-6-(4-fluorophenyl)-2,3-dihydroimidazo(2,1-b)-thiazole; 4-[6-(4-fluorophenyl)-2H,3H-imidazo[2,1-b][1,3]thiazol-5-yl]pyridine; 6-(4-fluorophenyl)-5-(4-pyridyl)-2,3-dihydroimidazo[2,1-b]thiazole; 6-(4-Fluorophenyl)-2,3-dihydro-5-(4-pyridyl)imidazo[2,1-b]thiazole; Imidazo(2,1-b)thiazole,; SK&F 86002
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MOA Modulator
External Link
CID: 49787172
TTD: D05VVX
 Compound Name RG7221 Phase 2 [14]
MOA Modulator
External Link
TTD: D06FTM
 Compound Name RO5520985 Phase 2 [15]
MOA Modulator
External Link
TTD: D0I8YS
 Compound Name SNN-0029 Phase 1/2 [16]
Synonyms
VEGF (intracerebroventricular, amyotrophic lateral sclerosis), NeuroNova/VIB/Genentech
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MOA Modulator
External Link
TTD: D0E7RQ
 Compound Name MP0250 Phase 1/2 [17]
MOA Inhibitor
External Link
TTD: D0ME7Q
 Compound Name AT001/r84 Phase 1 [18]
External Link
TTD: D0NO1A
 Compound Name MP-0112 Phase 1 [19]
Synonyms
DARPin (age related macular degeneration), Molecular Partners/Allergan; VEGF-A specific DARPin, Molecular Partners/Allergan
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MOA Inhibitor
External Link
CID: 10464700
TTD: D0V3HP
 Compound Name Navicixizumab Phase 1 [20]
External Link
TTD: D00IVN
 Compound Name SFLT-01 Phase 1 [21]
Synonyms
AAV2-sFLT-01; VEGF/PIGF suppression gene therapy (cancer), Genzyme; SFLT-01 gene therapy (wet AMD), AGTC/Genzyme; VEGF suppression gene therapy (wet age-related macular degeneration), Applied Genetic Technologies/ Genzyme
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MOA Modulator
External Link
TTD: D0YZ4T
 Compound Name ABI-011 Phase 1 [17]
MOA Inhibitor
External Link
TTD: D0P4KU
 Compound Name Carbamide derivative 17 Patented [22]
Synonyms
PMID28621580-Compound-WO2012089137c13
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MOA Inhibitor
External Link
TTD: D00ZFY
 Compound Name Carbamide derivative 16 Patented [22]
Synonyms
PMID28621580-Compound-WO2012028106c12
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MOA Inhibitor
External Link
TTD: D01CKB
 Compound Name Indoline derivative 18 Patented [22]
Synonyms
PMID28621580-Compound-WO2014086102c29
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MOA Inhibitor
External Link
TTD: D01DJZ
 Compound Name Antibodie derivative 11 Patented [22]
Synonyms
PMID28621580-Compound-WO2016059057
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External Link
TTD: D01IFD
 Compound Name Pyridine derivative 2 Patented [22]
Synonyms
PMID28621580-Compound-US20130096136c42
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MOA Inhibitor
Activity IC50 = 3 nM
External Link
CID: 71522446
TTD: D01OEF
 Compound Name Indoline derivative 16 Patented [22]
Synonyms
PMID28621580-Compound-WO2013037293c26
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MOA Inhibitor
Activity IC50 = 31 nM
External Link
TTD: D03HPW
 Compound Name Carbamide derivative 22 Patented [22]
Synonyms
PMID28621580-Compound-WO2014040243c18
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MOA Inhibitor
Activity IC50 = 15 to 1000 nM
External Link
TTD: D03SZN
 Compound Name Oxetane 3,3-dicarboxamide compound 1 Patented [22]
Synonyms
PMID28621580-Compound-WO2013032797c63
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MOA Inhibitor
External Link
TTD: D03VXQ
 Compound Name Conjugated 3-(indolyl)-and 3-(azaindolyl)-4-arylmaleimide compound 1 Patented [22]
Synonyms
PMID28621580-Compound-WO2012084683c62
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MOA Inhibitor
External Link
TTD: D04PKQ
 Compound Name 1,6-naphyridine-4-ketone fused heterocyclic derivative 1 Patented [22]
Synonyms
PMID28621580-Compound-WO2013097753c65
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MOA Inhibitor
External Link
TTD: D04UKD
 Compound Name Pyrimidine derivative 5 Patented [22]
Synonyms
PMID28621580-Compound-US20160096832c60
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MOA Inhibitor
External Link
TTD: D05GVV
 Compound Name PMID28621580-Compound-WO2013112959C68 Patented [22]
MOA Inhibitor
External Link
TTD: D05LBH
 Compound Name Carbamide derivative 23 Patented [22]
Synonyms
PMID28621580-Compound-WO2014201127c20
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MOA Inhibitor
External Link
TTD: D05WTW
 Compound Name Quinoline and quinazoline derivative 7 Patented [22]
Synonyms
PMID28621580-Compound-WO2013112950c37
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MOA Inhibitor
External Link
TTD: D06ARD
 Compound Name PMID28621580-Compound-WO2015089220C70 Patented [22]
MOA Inhibitor
External Link
TTD: D07AVU
 Compound Name Pyrimidine derivative 9 Patented [22]
Synonyms
PMID28621580-Compound-WO2010066684c55
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MOA Inhibitor
External Link
TTD: D07ESG
 Compound Name Quinoline and quinazoline derivative 4 Patented [22]
Synonyms
PMID28621580-Compound-WO2012127012c31
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MOA Inhibitor
External Link
TTD: D07UJJ
 Compound Name Pyridine derivative 5 Patented [22]
Synonyms
PMID28621580-Compound-WO2013015657c41
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MOA Inhibitor
External Link
TTD: D08INZ
 Compound Name Carbamide derivative 15 Patented [22]
Synonyms
PMID28621580-Compound-US20160096828c21
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MOA Inhibitor
Activity IC50 = 3 nM
External Link
TTD: D08XDA
 Compound Name Antibodie derivative 3 Patented [22]
Synonyms
PMID28621580-Compound-WO2012125123
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External Link
TTD: D09GWR
 Compound Name Pyrimidine derivative 7 Patented [22]
Synonyms
PMID28621580-Compound-US20169233968c59
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MOA Inhibitor
External Link
TTD: D09KYB
 Compound Name Carbamide derivative 18 Patented [22]
Synonyms
PMID28621580-Compound-WO2012094451c15
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MOA Inhibitor
External Link
TTD: D0A5NC
 Compound Name Indoline derivative 21 Patented [22]
Synonyms
PMID28621580-Compound-WO2015117551c25
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MOA Inhibitor
Activity IC50 = 65 nM
External Link
TTD: D0A8SH
 Compound Name Pyrimidine derivative 10 Patented [22]
Synonyms
PMID28621580-Compound-WO2014000686c53
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MOA Inhibitor
External Link
TTD: D0A9RY
 Compound Name Pyridine derivative 7 Patented [22]
Synonyms
PMID28621580-Compound-WO2013044362c44
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MOA Inhibitor
External Link
TTD: D0BA5J
 Compound Name Quinoline and quinazoline derivative 6 Patented [22]
Synonyms
PMID28621580-Compound-WO2013040515c36
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MOA Inhibitor
External Link
TTD: D0BL4H
 Compound Name Antibodie derivative 7 Patented [22]
Synonyms
PMID28621580-Compound-WO2014055998
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MOA Binder
External Link
TTD: D0CE1R
 Compound Name Antibodie derivative 2 Patented [22]
Synonyms
PMID28621580-Compound-WO2012088563
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MOA Binder
External Link
TTD: D0D0AX
 Compound Name Pyridine derivative 3 Patented [22]
Synonyms
PMID28621580-Compound-US20140336108c48
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MOA Inhibitor
External Link
TTD: D0D7SL
 Compound Name Pyridine derivative 8 Patented [22]
Synonyms
PMID28621580-Compound-WO2014029250c45
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MOA Inhibitor
External Link
TTD: D0DA6B
 Compound Name Carbamide derivative 19 Patented [22]
Synonyms
PMID28621580-Compound-WO2012139499c14
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MOA Inhibitor
External Link
TTD: D0DI5S
 Compound Name Indoline derivative 13 Patented [22]
Synonyms
PMID28621580-Compound-WO2012088506c23
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MOA Inhibitor
External Link
TTD: D0E5IJ
 Compound Name Pyrimidine derivative 11 Patented [22]
Synonyms
PMID28621580-Compound-WO2014139458c54
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MOA Inhibitor
External Link
TTD: D0EE3P
 Compound Name Pyrimidine derivative 8 Patented [22]
Synonyms
PMID28621580-Compound-US20169296747c52
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MOA Inhibitor
External Link
TTD: D0FK5P
 Compound Name Quinoline and quinazoline derivative 10 Patented [22]
Synonyms
PMID28621580-Compound-WO2014127335c34
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MOA Inhibitor
External Link
TTD: D0FK6Y
 Compound Name Quinoline and quinazoline derivative 8 Patented [22]
Synonyms
PMID28621580-Compound-WO2014113859c33
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MOA Inhibitor
External Link
TTD: D0FL6P
 Compound Name Pyridine derivative 10 Patented [22]
Synonyms
PMID28621580-Compound-WO2014040242c47
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MOA Inhibitor
External Link
TTD: D0FY2Q
 Compound Name Indoline derivative 14 Patented [22]
Synonyms
PMID28621580-Compound-WO2012139019c24
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MOA Inhibitor
External Link
TTD: D0HO5B
 Compound Name PMID28621580-Compound-WO2014079545C69 Patented [22]
MOA Inhibitor
External Link
TTD: D0HX9S
 Compound Name Carbamide derivative 14 Patented [22]
Synonyms
PMID28621580-Compound-US20140256819c19
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MOA Inhibitor
Activity IC50 = 460 nM
External Link
TTD: D0I6WJ
 Compound Name Pyridine derivative 11 Patented [22]
Synonyms
PMID28621580-Compound-WO2015075483c49
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MOA Inhibitor
External Link
TTD: D0IZ8B
 Compound Name Pyridine derivative 9 Patented [22]
Synonyms
PMID28621580-Compound-WO2014029251c46
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MOA Inhibitor
External Link
TTD: D0KW0F
 Compound Name Quinoline and quinazoline derivative 5 Patented [22]
Synonyms
PMID28621580-Compound-WO2012171487c32
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MOA Inhibitor
External Link
TTD: D0M2XJ
 Compound Name Pyridine derivative 4 Patented [22]
Synonyms
PMID28621580-Compound-WO2012169934c40
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MOA Inhibitor
Activity IC50 = 32 nM
External Link
TTD: D0M9KZ
 Compound Name Quinoline and quinazoline derivative 3 Patented [22]
Synonyms
PMID28621580-Compound-US20150158854c39
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MOA Inhibitor
External Link
TTD: D0MA6I
 Compound Name Quinoline and quinazoline derivative 2 Patented [22]
Synonyms
PMID28621580-Compound-US20130165458c38
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MOA Inhibitor
External Link
TTD: D0O5IA
 Compound Name Indoline derivative 17 Patented [22]
Synonyms
PMID28621580-Compound-WO2014086102c28
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MOA Inhibitor
External Link
TTD: D0O8RZ
 Compound Name Indoline derivative 19 Patented [22]
Synonyms
PMID28621580-Compound-WO2014102377c27
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MOA Inhibitor
External Link
TTD: D0Q4XV
 Compound Name Pyridine derivative 6 Patented [22]
Synonyms
PMID28621580-Compound-WO2013044361c43
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MOA Inhibitor
External Link
TTD: D0S4XH
 Compound Name Quinoline and quinazoline derivative 9 Patented [22]
Synonyms
PMID28621580-Compound-WO2014127214c35
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MOA Inhibitor
External Link
TTD: D0SH2Y
 Compound Name 3-phenyl-5-ureidoisothiazole-4-carboximide and 3-amino-5-phenylisothiazole derivative 1 Patented [22]
Synonyms
PMID28621580-Compound-WO2013101954c67
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MOA Inhibitor
External Link
TTD: D0T1GG
 Compound Name PMID28621580-Compound-WO2013036866C66 Patented [22]
MOA Inhibitor
External Link
TTD: D0T9DV
 Compound Name Antibodie derivative 8 Patented [22]
Synonyms
PMID28621580-Compound-WO2014081202
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MOA Disrupter
External Link
TTD: D0U6PW
 Compound Name Pyrimidine derivative 6 Patented [22]
Synonyms
PMID28621580-Compound-US20160096837c61
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MOA Inhibitor
External Link
TTD: D0V7OF
 Compound Name Carbamide derivative 20 Patented [22]
Synonyms
PMID28621580-Compound-WO2013037292c17
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MOA Inhibitor
External Link
CID: 60171803
TTD: D0VI1V
 Compound Name Indoline derivative 15 Patented [22]
Synonyms
PMID28621580-Compound-WO2012139019c25
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MOA Inhibitor
Activity IC50 = 65 nM
External Link
TTD: D0VX5Y
 Compound Name Antibodie derivative 9 Patented [22]
Synonyms
PMID28621580-Compound-WO2016044219
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MOA Stablizer
External Link
TTD: D0WL5P
 Compound Name Antibodie derivative 1 Patented [22]
Synonyms
PMID28621580-Compound-WO2012004631
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MOA Blocker
External Link
TTD: D0X2BP
 Compound Name Indoline derivative 20 Patented [22]
Synonyms
PMID28621580-Compound-WO2015117551c24
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MOA Inhibitor
External Link
TTD: D0X2MF
 Compound Name Carbamide derivative 21 Patented [22]
Synonyms
PMID28621580-Compound-WO2013107225c16
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MOA Inhibitor
External Link
TTD: D0XS0Z
 Compound Name Antibodie derivative 4 Patented [22]
Synonyms
PMID28621580-Compound-WO2012161372
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MOA Inhibitor
External Link
TTD: D0Y2IV
 Compound Name Indoline derivative 12 Patented [22]
Synonyms
PMID28621580-Compound-WO2012088506c22
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MOA Inhibitor
External Link
TTD: D0Z0SY
 Compound Name Oxetane 3,3-dicarboxamide compound 2 Patented [22]
Synonyms
PMID28621580-Compound-WO2013032797c64
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MOA Inhibitor
External Link
TTD: D0ZE2J
 Compound Name Bevasiranib Discontinued in Phase 3 [23]
MOA Modulator
External Link
TTD: D0YG4I
 Compound Name ALN-VEG01 Terminated [24]
Synonyms
RNAi therapeutics (ocular disease), Alnylam; VEGF-silencing siRNAs, Alnylam; Vascular endothelial growth factor gene-silencing siRNAs, Alnylam; RNAi therapeutics (ocular disease), Alnylam/Merck; VEGF-silencing siRNAs, Alnylam/Merck; Vascular endothelial growth factor-silencing siRNAs, Alnylam/Merck
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External Link
TTD: D05ITS
References
Ref 1 PCA-1/ALKBH3 contributes to pancreatic cancer by supporting apoptotic resistance and angiogenesis. Cancer Res. 2012 Sep 15;72(18):4829-39. doi: 10.1158/0008-5472.CAN-12-0328. Epub 2012 Jul 23.
Ref 2 ALKBH3 contributes to survival and angiogenesis of human urothelial carcinoma cells through NADPH oxidase and tweak/Fn14/VEGF signals. Clin Cancer Res. 2012 Oct 1;18(19):5247-55. doi: 10.1158/1078-0432.CCR-12-0955. Epub 2012 Jul 31.
Ref 3 METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N(6) -methyladenosine-dependent primary MicroRNA processing. Hepatology. 2017 Feb;65(2):529-543. doi: 10.1002/hep.28885. Epub 2016 Dec 24.
Ref 4 The MCM3AP-AS1/miR-126/VEGF axis regulates cancer cell invasion and migration in endometrioid carcinoma. World J Surg Oncol. 2021 Jul 13;19(1):213. doi: 10.1186/s12957-021-02316-0.
Ref 5 Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina. 2006 Oct;26(8):859-70. doi: 10.1097/01.iae.0000242842.14624.e7.
Ref 6 FDA Approved Drug Products from FDA Official Website. 2004. Application Number: (ANDA) 125085.
Ref 7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
Ref 8 Faricimab: an investigational agent targeting the Tie-2/angiopoietin pathway and VEGF-A for the treatment of retinal diseases. Expert Opin Investig Drugs. 2021 Mar;30(3):193-200.
Ref 9 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 10 Clinical pipeline report, company report or official report of Roche (2009).
Ref 11 Clinical pipeline report, company report or official report of Genentech (2009).
Ref 12 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 13 Phase I and pharmacokinetic trial of PTC299 in pediatric patients with refractory or recurrent central nervous system tumors: a PBTC study. J Neurooncol. 2015 Jan;121(1):217-24. doi: 10.1007/s11060-014-1665-1. Epub 2014 Nov 19.
Ref 14 Bispecific antibodies and their applications
Ref 15 Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801. doi: 10.1038/nrd4478.
Ref 16 Clinical pipeline report, company report or official report of Neuronova.
Ref 17 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 18 Clinical pipeline report, company report or official report of Affitech (2011).
Ref 19 Treatment of exudative age-related macular degeneration with a designed ankyrin repeat protein that binds vascular endothelial growth factor: a phase I/II study. Am J Ophthalmol. 2014 Oct;158(4):724-732.e2.
Ref 20 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 21 sFLT01: a novel fusion protein with antiangiogenic activity. Mol Cancer Ther. 2011 Mar;10(3):404-15. doi: 10.1158/1535-7163.MCT-10-0813. Epub 2011 Jan 20.
Ref 22 VEGFR-2 inhibitors and the therapeutic applications thereof: a patent review (2012-2016). Expert Opin Ther Pat. 2017 Sep;27(9):987-1004. doi: 10.1080/13543776.2017.1344215. Epub 2017 Jun 23.
Ref 23 Bevasiranib for the Treatment of Wet, Age-Related Macular Degeneration
Ref 24 TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751.