m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT06015
 [1]
m6A modification INSR INSR METTL3 Methylation : m6A sites Direct Enhancement DNA methylation DNMT1 INSR
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Insulin receptor (INSR)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type DNA methylation (DNAMeth)
Epigenetic Regulator DNA (cytosine-5)-methyltransferase 1 (DNMT1) WRITER View Details
Regulated Target Insulin receptor (INSR) View Details
Crosstalk Relationship m6A  →  DNA methylation Enhancement
Crosstalk Mechanism m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases.
Crosstalk Summary METTL3-METTL14 recruits the DNA methyltransferase DNMT1 to chromatin for gene-body methylation including Notch2, Eomes, Insulin receptor (INSR) and Smad3, whose expression is fine-tuned by both gene-body 5mC, which promotes transcription, and m6A, which destabilizes transcripts. We demonstrate that METTL3-METTL14-dependent 5mC and m6A are both essential for the differentiation of embryonic stem cells into embryoid bodies and that the upregulation of key differentiation genes during early differentiation depends on the dynamic balance between increased 5mC and decreased m6A.
Cell Process Cell differentiation
In-vitro Model
 HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
HEK293T Normal Homo sapiens CVCL_0063
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
DNA (cytosine-5)-methyltransferase 1 (DNMT1) 27 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name SGI110 Phase 3 [2]
MOA Modulator
External Link
CID: 137295284
TTD: D0Q5KZ
 Compound Name Guadecitabine Phase 3 [3]
Synonyms
UNII-2KT4YN1DP7; 929901-49-5; 2KT4YN1DP7; SGI-110 free acid; Guadecitabine [USAN:INN]; GuadecitabineSGI-110; Guadecitabine (USAN/INN); CHEMBL3544916; Guanosine, 2'-deoxy-5-azacytidylyl-(3'-5')-2'-deoxy-; ZINC43203165; AKOS027321496; AKOS030238181; DB11918; CS-3089; HY-13542; D10877; 2'-deoxy-5-azacytidylyl-(3'-5')-2'-deoxyguanosine
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 135564655
TTD: D0VZ4N
DrugBank: DB11918
 Compound Name CC-486 Phase 3 [4]
Synonyms
AG-14361; AG14361; 328543-09-5; UNII-48N0U0K50I; AG 14361; CHEMBL65892; 48N0U0K50I; Imidazo[4,5,1-jk][1,4]benzodiazepin-7(4H)-one, 2-[4-[(dimethylamino)methyl]phenyl]-5,6-dihydro-; AG-014361; 1-(4-((dimethylamino)methyl)phenyl)-8,9-dihydro-2,7,9a-triazabenzo[cd]azulen-6(7H)-one; Imidazo(4,5,1-jk)(1,4)benzodiazepin-7(4H)-one, 2-(4-((dimethylamino)methyl)phenyl)-5,6-dihydro-; 2-[4-[(Dimethylamino)methyl]phenyl]-5,6-dihydroimidazo[4,5,1-jk][1,4]benzodiazepin-7(4H)-one; SMR000486393; MLS006011157; MLS001065917; Nucleoside analogue
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MOA Inhibitor
External Link
CID: 9840076
TTD: D09NTC
 Compound Name S-110 Phase 3 [5]
Synonyms
DNA demethylating agent (myelodysplastic syndrome), Supergen
    Click to Show/Hide
MOA Inhibitor
External Link
TTD: D0A2BO
 Compound Name Palifosfamide Phase 2 [6]
Synonyms
ZIO-201
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 100427
TTD: D04FDN
DrugBank: DB05668
 Compound Name RX-3117 Phase 2 [7]
Synonyms
Antimetabolite (cancer), Rexahn; Antimetabolite (cancer), Rexahn/ Teva
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 11242315
TTD: D0L7WS
 Compound Name Antroquinonol Phase 2 [8]
Synonyms
Hocena; Fungal extract (cancer), Golden Biotechnology
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 24875259
TTD: D0T3AW
DrugBank: DB12326
 Compound Name GSK4172239 Phase 1 [9]
MOA Inhibitor
External Link
TTD: D5QR2M
 Compound Name PMID27376512-Compound-miR-155-5p Patented [10]
MOA Inhibitor
Activity Ki = 27.88 nM
External Link
TTD: D01CGQ
 Compound Name PMID27376512-Compound-Table1Example11 Patented [10]
MOA Inhibitor
Activity IC50 = 39440 nM
External Link
CID: 75201485
TTD: D04JIH
 Compound Name PMID27376512-Compound-Table1Example16 Patented [10]
MOA Inhibitor
Activity IC50 = 22520 nM
External Link
CID: 75201537
TTD: D05DSL
 Compound Name PMID27376512-Compound-Table1Example5 Patented [10]
MOA Inhibitor
Activity IC50(DNMT1) = 3530 nM
External Link
CID: 73774653
TTD: D09FMS
 Compound Name PMID27376512-Compound-asCEBP-2HPE Patented [10]
MOA Inhibitor
Activity Ki = 135.2 nM
External Link
TTD: D0E7OA
 Compound Name PMID27376512-Compound-asCEBP-1 Patented [10]
MOA Inhibitor
Activity Ki = 2003 nM
External Link
TTD: D0G6ON
 Compound Name PMID27376512-Compound-Table1Example4 Patented [10]
MOA Inhibitor
Activity IC50 = 13810 nM
External Link
CID: 75201432
TTD: D0K4YF
 Compound Name PMID27376512-Compound-asCEBP-2 Patented [10]
MOA Inhibitor
Activity Ki = 434.1 nM
External Link
TTD: D0KE4E
 Compound Name PMID27376512-Compound-asCEBP-1HPE Patented [10]
MOA Inhibitor
Activity Ki = 917.5 nM
External Link
TTD: D0LK4R
 Compound Name PMID27376512-Compound-Table1Example8 Patented [10]
MOA Inhibitor
Activity IC50 = 6850 nM
External Link
CID: 75201482
TTD: D0RT6C
 Compound Name PMID27376512-Compound-MTC-433 Patented [10]
MOA Inhibitor
Activity IC50 = 4.22 nM
External Link
TTD: D0U5CK
 Compound Name PMID27376512-Compound-Table1Example30 Patented [10]
MOA Inhibitor
External Link
CID: 75201638
TTD: D0YK6K
 Compound Name PMID27376512-Compound-MTC-424 Patented [10]
MOA Inhibitor
Activity IC50 = 1940 nM
External Link
TTD: D02WRM
 Compound Name PMID27376512-Compound-MTC-427 Patented [10]
MOA Inhibitor
Activity IC50 = 295 nM
External Link
TTD: D0HA0J
 Compound Name PMID27376512-Compound-MTC-422 Patented [10]
MOA Inhibitor
Activity IC50 = 1430 nM
External Link
TTD: D0QY0N
 Compound Name PMID27376512-Compound-MTC-423 Patented [10]
MOA Inhibitor
Activity IC50 = 363 nM
External Link
TTD: D0W9VZ
 Compound Name PMX-700 Investigative [11]
Synonyms
SJ-005019; SJ-005059; DC-010-116; Temozolomide analogs (cancer), Pharminox
    Click to Show/Hide
MOA Modulator
External Link
TTD: D03DTQ
 Compound Name XB-05 Investigative [11]
MOA Inhibitor
External Link
TTD: D0JV8Q
 Compound Name CP-4200 Investigative [11]
Synonyms
Lipidated azacitidine (cancer, Lipid Vector), Clavis Pharma; 5-azacytidine-5'-elaidate
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MOA Inhibitor
External Link
TTD: D0OT1S
Insulin receptor (INSR) 48 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Human neutral insulin Approved [12]
MOA Binder
External Link
CID: 16129672
TTD: D02EHV
 Compound Name Insulin Lyspro recombinant Approved [12]
MOA Binder
External Link
TTD: D03VXG
 Compound Name Insulin, porcine Approved [13]
Synonyms
Velosulin; Hog insulin; Insulin [pig]; Insulin porcine; Neutral insulin; Pig insulin; Porcine insulin; Swine insulin; A neutral, buffered solution of pork insulin; Insulin (Alopex lagopus); Insulin (Canis familiaris); Insulin (Physeter catodon); Insulin (dog); Insulin (ox); Insulin (pig); Insulin (porcine); Insulin (sperm whale); Insulin (swine); Insulin [USAN:JAN]; Insulin, neutral; Insulin,pig; Insulin (Ox), 8A-L-threonine-10A-L-isoleucine-(9CI); 8A-L-Threonine-10A-L-isoleucineinsulin (ox)
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MOA Binder
External Link
CID: 16131098
TTD: D05ELO
 Compound Name Insulin recombinant Approved [12]
Synonyms
Exubera; Endopancrine; Humilin; Dermulin; Decurvon; Musulin; Iszilin; Insulyl; Insular; Iletin; insulin-human; Dal-insulinum; Intesulin B; Insulin, dalanated; Insulina dalanatada; AERx; Insulinum dalanatum; insulin (recombinant); Imusay-131; INSULIN INJECTION; Insulini injectio neutralis; Insulina iniettabile neutra; Injectable insulini neutrale; Inyectable neutro de insulina; CHEBI:5931; CCRIS 5464; Insulinum dalanatum [INN-Latin]; HSDB 3102; Insulin, dalanated [USAN:INN]; AERx [Insulin management system]
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MOA Binder
External Link
CID: 70678557
TTD: D06SVW
 Compound Name Metformin arginine-hemisuccinimide Approved [14]
Synonyms
Diap-2; Metformin arginine-hemisuccinate-hemisuccinamide; Metformin arginine-hemisuccinimide (type 2 diabetes); Diap-2 (type 2 diabetes), Arteria; Metformin arginine-hemisuccinimide (type 2 diabetes), Arteria
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MOA Inhibitor
External Link
TTD: D09PPG
 Compound Name Insulin-lispro Approved [15]
Synonyms
WNRQPCUGRUFHED-DETKDSODSA-N; Insulin lispro [USAN:BAN:INN]; Humalog (TN); Insulin Lispro
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MOA Binder
External Link
CID: 16132438
TTD: D0L6JE
 Compound Name Insulin-glulisine Approved [16]
MOA Binder
External Link
CID: 16136701
TTD: D0M2XE
 Compound Name Ryzodeq Approved [17]
MOA Modulator
External Link
TTD: D0Y3VQ
 Compound Name Meglitinides Approved [18]
MOA Stimulator
External Link
CID: 3033769
TTD: D07MEH
DrugBank: DB12518
 Compound Name NN5401 Phase 3 [17]
Synonyms
Insulin degludec and insulin aspart; Ryzodeg (TN)
    Click to Show/Hide
MOA Modulator
External Link
TTD: D0U8YK
 Compound Name Metformin glycinate Phase 2/3 [19]
Synonyms
DMMET-01; Metformin glycinate (diabetes); Type 2 diabetes therapy, Laboratorios Silanes; Metformin glycinate (diabetes), Laboratorios Silanes
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MOA Inhibitor
External Link
CID: 44520175
TTD: D0U3LK
 Compound Name MSDC-0602 Phase 2 [20]
Synonyms
1133819-87-0; MSDC 0602; 5-(4-(2-(3-methoxyphenyl)-2-oxoethoxy)benzyl)thiazolidine-2,4-dione; 2,4-Thiazolidinedione, 5-[[4-[2-(3-methoxyphenyl)-2-oxoethoxy]phenyl]methyl]-; YAUMOGALQJYOJQ-UHFFFAOYSA-N; SCHEMBL623654; AKOS027382993
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MOA Modulator
External Link
CID: 25230266
TTD: D00AUX
 Compound Name S-707106 Phase 2 [17]
MOA Modulator
External Link
TTD: D02SXZ
 Compound Name NP-01 Phase 2 [17]
Synonyms
Vanadium (buccal, nanodroplet emulsion (Aonys), type 2 diabetes/metabolic syndrome), Medesis
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MOA Agonist
External Link
TTD: D03VCJ
 Compound Name DM-99 Phase 2 [17]
MOA Agonist
External Link
TTD: D06MOY
 Compound Name VVP-808 Phase 2 [17]
Synonyms
Insulin sensitizer (type 2 diabetes), Verva Pharmaceuticals
    Click to Show/Hide
MOA Modulator
External Link
TTD: D07NKZ
 Compound Name TAK-379 Phase 2 [17]
Synonyms
Insulin sensitizer (oral, diabetes mellitus), Takeda
    Click to Show/Hide
MOA Modulator
External Link
TTD: D0A6OS
 Compound Name EGS-21 Phase 2 [21]
Synonyms
Glucocerebroside, Enzo; Glucosylceramide, Enzo Biochem
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MOA Modulator
External Link
CID: 6475228
TTD: D0D4ZW
 Compound Name DM-71 Phase 2 [17]
Synonyms
Insulin sensitizer (type 2 diabetes), DiaMedica; Bethanechol + n-acetyl cysteine (type 2 diabetes), DiaMedica
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MOA Modulator
External Link
TTD: D0T5YX
 Compound Name Tesofensine Phase 2 [22]
Synonyms
NS-2330
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 11370864
TTD: D0ZK7B
DrugBank: DB06156
 Compound Name RZ358 Phase 2 [23]
External Link
TTD: DJM3W0
 Compound Name Mitoglitazone Phase 2 [24]
Synonyms
MSDC-0160; Mitoglitazone (TN)
    Click to Show/Hide
MOA Modulator
External Link
CID: 10429242
TTD: D00SWQ
DrugBank: DB11721
 Compound Name AGT-182 Phase 1 [17]
Synonyms
HIRMAb-IDUS; Iduronidase/human insulin receptor-targeting chimeric mAb fusion protein (imucopolysaccharidosis type II), ArmaGen
    Click to Show/Hide
External Link
TTD: D06HPP
 Compound Name ISF-402 Phase 1 [25]
Synonyms
Urinary tetrapeptide (diabetes), Monash University/International Diabetes Institute/Pallane; Urinary tetrapeptide (diabetes), Monash University/International Diabetes Institute/Dia-B Tech Ltd
    Click to Show/Hide
MOA Modulator
External Link
TTD: D07DLA
 Compound Name Insulin transdermal Phase 1 [26]
MOA Modulator
External Link
TTD: D08TGG
 Compound Name NN-1218 Application submitted [27]
MOA Modulator
External Link
TTD: D08XFJ
 Compound Name Insulin oral sublingual Phase 1 [17]
MOA Modulator
External Link
TTD: D0D5EJ
 Compound Name AEW-541 Phase 1 [28]
Synonyms
AECDBHGVIIRMOI-UHFFFAOYSA-N; NVP-AEW541; 475489-16-8; 475488-34-7; AEW541; NVP-AEW 541; UNII-97QB5037VR; AEW 541; AVP-AEW541; 7-((1s,3s)-3-(azetidin-1-ylmethyl)cyclobutyl)-5-(3-(benzyloxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine; CHEMBL1614712; 97QB5037VR; 7-[TRANS-3-(1-AZETIDINYLMETHYL)CYCLOBUTYL]-5-[3-(PHENYLMETHOXY)PHENYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE; C27H29N5O; 7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE, 7-[CIS-3-(1-AZETIDINYLMETHYL)CYCLOBUTYL]-5-[3-(PHENYLMETHOXY)PHENYL]-
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 244 nM
External Link
CID: 11476171
TTD: D07HPJ
 Compound Name AKP-020 Discontinued in Phase 2 [29]
Synonyms
BEOV; Bis(ethylmaltolato)oxovanadium IV; Insulin enhancer (oral, type 2 diabetes), Akesis Pharmaceuticals
    Click to Show/Hide
MOA Enhancer
External Link
TTD: D05LSY
 Compound Name EML-336 Discontinued in Phase 2 [17]
Synonyms
CRE-16336; EML-16336; ONO-5816
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MOA Modulator
External Link
TTD: D0F1MU
 Compound Name DM-83 Discontinued in Phase 2 [17]
MOA Stimulator
External Link
TTD: D0Z8UQ
 Compound Name KW-2450 Discontinued in Phase 1/2 [30]
MOA Modulator
External Link
CID: 56847547
TTD: D0M3OR
 Compound Name CLX-0900 Terminated [31]
Synonyms
CLX-0900E
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MOA Modulator
External Link
TTD: D02IJP
 Compound Name TER-16998 Terminated [17]
Synonyms
TER-17411; TER-17529; TLK-16998; TLK-17411; TLK-19780; TLK-19781; Insulin receptor activators (oral, diabetes mellitus); Insulin receptor activators (oral, diabetes mellitus), ReceptorBio; Insulin receptor activators (oral, diabetes), Telik/Sanwa
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MOA Activator
External Link
TTD: D03CMR
 Compound Name XMetD Investigative [17]
Synonyms
Insulin receptor antagonist antibody (hypoglycemia), XOMA
    Click to Show/Hide
External Link
TTD: D02QOL
 Compound Name FPT-038 Investigative [17]
Synonyms
Hypoglycemic recombinant secreted protein (type 2 diabetes), Five Prime Therapeutics
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MOA Modulator
External Link
TTD: D03BCE
 Compound Name Quick-acting insulin Investigative [17]
Synonyms
Quick-acting insulin (injectable, diabetes)
    Click to Show/Hide
MOA Modulator
External Link
TTD: D08ZLL
 Compound Name XMetS Investigative [17]
Synonyms
Insulin receptor sensitizing antibody (diabetes), XOMA
    Click to Show/Hide
External Link
TTD: D0C7QW
 Compound Name RHIIP Investigative [32]
MOA Modulator
External Link
TTD: D0I4LQ
 Compound Name AD10-1025 Investigative [17]
Synonyms
AD10-369; AD10-371; AD10-797; AD10-798; Partial PPAR gamma agonist (oral, type 2 diabetes); Partial PPAR gamma agonist (oral, type 2 diabetes), Adamed SP; Phenyl propionic acid derivative 3 (oral, type 2 diabetes), Adamed SP; PPAR modulators (oral, hypercholesterolemia/NIDDM), Adamed
    Click to Show/Hide
MOA Agonist
External Link
TTD: D0KC9V
 Compound Name NVP-TAE684 Investigative [33]
Synonyms
761439-42-3; NVP-TAE 684; TAE684; TAE-684; 5-chloro-N4-(2-(isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidine-2,4-diamine; TAE684 (NVP-TAE684); TAE 684; UNII-EH1713MN4K; CHEMBL509032; EH1713MN4K; 5-Chloro-N2-[2-methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-2,4-pyrimidinediamine; C30H40ClN7O3S
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 43.7 nM
External Link
CID: 16038120
TTD: D0R2WK
 Compound Name DC-9703 Investigative [17]
MOA Modulator
External Link
TTD: D0XQ0V
 Compound Name VVP-100X Investigative [17]
MOA Inhibitor
External Link
TTD: D0YN9H
 Compound Name 4-((naphthalen-2-ylamino)methyl)benzene-1,2-diol Investigative [34]
Synonyms
CHEMBL1240677; BDBM50326006
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 5150 nM
External Link
CID: 43680262
TTD: D0L7MM
 Compound Name 4-((1H-indazol-6-ylamino)methyl)benzene-1,2-diol Investigative [34]
Synonyms
CHEMBL1240676; BDBM50326004
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 2250 nM
External Link
CID: 43743432
TTD: D0W9KO
 Compound Name PMID24900237C15 Investigative [35]
Synonyms
1022957-12-5; GTPL8220; BDBM50385590; KB-75520
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MOA Inhibitor
Activity IC50 = 597 nM
External Link
CID: 25229528
TTD: D0G4CS
 Compound Name L-betagamma-meATP Investigative [36]
Synonyms
UFZTZBNSLXELAL-IOSLPCCCSA-N; AMP-PCP; beta,gamma-Methylene ATP; phosphomethylphosphonic acid adenylate ester; CHEMBL133463; CHEBI:40532; 5'-O-(hydroxy{[hydroxy(phosphonomethyl)phosphoryl]oxy}phosphoryl)adenosine; ADENOSINE 5'-[BETA,GAMMA-METHYLENE]TRIPHOSPHATE; ADENOSINE-5'-[BETA, GAMMA-METHYLENE]TRIPHOSPHATE; 3469-78-1; adenosine 5'-beta,gamma-mu-methylenetriphosphate; ({[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}methyl)phosphonic acid; AMPPCP; betagamma-methylene-adenosine 5'-triphosphate
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 91532
TTD: D0UG4S
DrugBank: DB03909
 Compound Name GSK-1838705A Investigative [37]
Synonyms
GSK 1838705A; GSK1838705A
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MOA Inhibitor
Activity IC50 = 79 nM
External Link
CID: 25182616
TTD: D06PJW
References
Ref 1 Fine-tuning of gene expression through the Mettl3-Mettl14-Dnmt1 axis controls ESC differentiation. Cell. 2025 Feb 20;188(4):998-1018.e26. doi: 10.1016/j.cell.2024.12.009. Epub 2025 Jan 17.
Ref 2 Immunomodulatory action of the DNA methyltransferase inhibitor SGI-110 in epithelial ovarian cancer cells and xenografts. Epigenetics. 2015;10(3):237-46.
Ref 3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 4 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 5 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 6 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 7 Metabolism, mechanism of action and sensitivity profile of fluorocyclopentenylcytosine (RX-3117; TV-1360). Invest New Drugs. 2013 Dec;31(6):1444-57.
Ref 8 Antroquinonol D, isolated from Antrodia camphorata, with DNA demethylation and anticancer potential. J Agric Food Chem. 2014 Jun 18;62(24):5625-35.
Ref 9 Clinical pipeline report, company report or official report of GlaxoSmithKline
Ref 10 DNA methyltransferase inhibitors: an updated patent review (2012-2015). Expert Opin Ther Pat. 2016 Sep;26(9):1017-30. doi: 10.1080/13543776.2016.1209488. Epub 2016 Jul 18.
Ref 11 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 12 Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
Ref 13 Acidic residues on the N-terminus of proinsulin C-Peptide are important for the folding of insulin precursor. J Biochem. 2002 Jun;131(6):855-9.
Ref 14 Metformin (Glucophage) inhibits tyrosine phosphatase activity to stimulate the insulin receptor tyrosine kinase. Biochem Pharmacol. 2004 Jun 1;67(11):2081-91.
Ref 15 Hope for insulin mimetic oral antidiabetic drugs. Eur J Endocrinol. 1999 Dec;141(6):561-2.
Ref 16 Insulin glulisine: a review of its use in the management of diabetes mellitus. Drugs. 2009;69(8):1035-57.
Ref 17 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: 1800).
Ref 18 New drugs for type 2 diabetes mellitus: what is their place in therapy Drugs. 2008;68(15):2131-62.
Ref 19 Effect of Metformin Glycinate on Glycated Hemoglobin A1c Concentration and Insulin Sensitivity in Drug-Naive Adult Patients with Type 2 Diabetes Mellitus. Diabetes Technol Ther. 2012 December; 14(12): 1140-1144.
Ref 20 Insulin resistance and metabolic derangements in obese mice are ameliorated by a novel peroxisome proliferator-activated receptor gamma-sparing thiazolidinedione. J Biol Chem. 2012 Jul 6;287(28):23537-48.
Ref 21 Ceramides and glucosylceramides are independent antagonists of insulin signaling. J Biol Chem. 2014 Jan 10;289(2):723-34.
Ref 22 The novel triple monoamine reuptake inhibitor tesofensine induces sustained weight loss and improves glycemic control in the diet-induced obese rat: comparison to sibutramine and rimonabant. Eur J Pharmacol. 2010 Jun 25;636(1-3):88-95.
Ref 23 Clinical pipeline report, company report or official report of Rezolute
Ref 24 An evaluation of MSDC-0160, a prototype mTOT modulating insulin sensitizer, in patients with mild Alzheimer's disease. Curr Alzheimer Res. 2014;11(6):564-73.
Ref 25 Ability of GHTD-amide and analogs to enhance insulin activity through zinc chelation and dispersal of insulin oligomers. Peptides. 2009 Jun;30(6):1088-97.
Ref 26 Transdermal drug delivery of insulin with ultradeformable carriers. Clin Pharmacokinet. 2003;42(5):461-74.
Ref 27 Ultrafast-Acting Insulins: State of the Art. J Diabetes Sci Technol. 2012 July; 6(4): 728-742.
Ref 28 Inhibition of the insulin-like growth factor-1 receptor (IGF1R) tyrosine kinase as a novel cancer therapy approach. J Med Chem. 2009 Aug 27;52(16):4981-5004.
Ref 29 Effect of vanadium on insulin and leptin in Zucker diabetic fatty rats. Mol Cell Biochem. 2001 Feb;218(1-2):93-6.
Ref 30 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics. 2005 Aug;86(2):127-41. doi: 10.1016/j.ygeno.2005.04.008.
Ref 31 CLX-0901 (Calyx Therapeutics). Curr Opin Investig Drugs. 2001 May;2(5):650-3.
Ref 32 PROMAXX inhaled insulin: safe and efficacious administration with a commercially available dry powder inhaler. Diabetes Obes Metab. 2009 May;11(5):455-9.
Ref 33 Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):270-5.
Ref 34 ATP non-competitive IGF-1 receptor kinase inhibitors as lead anti-neoplastic and anti-papilloma agents. Eur J Pharmacol. 2007 May 7;562(1-2):1-11. doi: 10.1016/j.ejphar.2007.01.052. Epub 2007 Feb 3.
Ref 35 Discovery of a potent inhibitor of anaplastic lymphoma kinase with in vivo antitumor activity. ACS Med Chem Lett. 2010 Sep 1;1(9):493-8.
Ref 36 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 37 GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers. Mol Cancer Ther. 2009 Oct;8(10):2811-20.