m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05083
 [1]
Non-coding RNA DRAIC HNRNPA2B1  lncRNA       miRNA   circRNA Direct Enhancement m6A modification IGF1R IGF1R hnRNPA2B1 : m6A sites
m6A Modification:
m6A Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
m6A Target Insulin-like growth factor 1 receptor (IGF1R)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator Downregulated RNA in cancer, inhibitor of cell invasion and migration (DRAIC) LncRNA View Details
Regulated Target Heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) View Details
Crosstalk Relationship ncRNA  →  m6A Enhancement
Crosstalk Mechanism ncRNAs directly impacts m6A modification through recruiting m6A regulator
Crosstalk Summary DRAIC mediates HNRNPA2B1 stability and m6A-modified Insulin-like growth factor 1 receptor (IGF1R) instability to inhibit tumor progression
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Insulin-like growth factor 1 receptor (IGF1R) 38 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Teprotumumab Approved [2]
Synonyms
RV001
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MOA Antagonist
External Link
TTD: D0EN0W
 Compound Name Mecasermin Approved [3]
Synonyms
Increlex (TN)
    Click to Show/Hide
MOA Inhibitor
External Link
TTD: D0F3JT
 Compound Name Somatomedin-1 Approved [4]
Synonyms
Igef (TN)
    Click to Show/Hide
MOA Modulator
External Link
TTD: D0N3NZ
 Compound Name OSI-906 Phase 3 [5]
Synonyms
Linsitinib; 867160-71-2; Linsitinib(OSI-906); OSI906; OSI 906; OSI-906AA; OSI-906 (Linsitinib); UNII-15A52GPT8T; Kinome_3532; ASP-7487; 3-[8-amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutan-1-ol; 15A52GPT8T; CHEMBL1091644; MMV676605; cis-3-[8-Amino-1-(2-phenyl-7-quinolinyl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutanol; C26H23N5O; cis-3-(8-amino-1-(2-phenyl-7-quinolinyl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanol; Linsitinib [USAN:INN]; OSI906/Linsitinib/
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 13 nM
External Link
CID: 11640390
TTD: D01GFX
DrugBank: DB06075
 Compound Name Rinfabate Phase 2/3 [6]
Synonyms
RhIGFBP-3; Rinfabate, Insmed; RhIGF-BP3, Insmed; Insulin-like growth factor binding protein-3, Insmed
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MOA Modulator
External Link
TTD: D06APK
 Compound Name AMG 479 Phase 2 [7]
MOA Inhibitor
External Link
TTD: D00AKR
 Compound Name VPI-2690B Phase 2 [8]
MOA Antagonist
External Link
TTD: D00VKK
 Compound Name AXL-1717 Phase 2 [9]
Synonyms
BVT-51004; IGF-1 inhibitors, Axelar/Biovitrum; IGF-1 inhibitors, Karolinska/Biovitrum; Insulin-like growth factor 1 inhibitors, Axelar/Biovitrum
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MOA Inhibitor
External Link
CID: 72435
TTD: D01SJS
DrugBank: DB12802
 Compound Name R1507 Phase 2 [10]
MOA Inhibitor
External Link
CID: 5376617
TTD: D03BHM
 Compound Name Cixutumumab Phase 2 [11]
Synonyms
LY3012217
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MOA Modulator
External Link
TTD: D0E5DP
 Compound Name TT-100 Phase 2 [12]
Synonyms
TT-100, TriAct; Dual IGF-1/EGFR inhibitor (non-small-cell lung cancer), TriAct
    Click to Show/Hide
MOA Inhibitor
External Link
TTD: D0T5JS
 Compound Name MM-141 Phase 2 [13]
MOA Modulator
External Link
TTD: D00BUO
 Compound Name Cyclolignan picropodophyllin Phase 1 [14]
Synonyms
PPP; IGF-1R inhibitor (cancer), Karolinska
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MOA Inhibitor
External Link
TTD: D01OYS
 Compound Name RG-7010 Phase 1 [15]
Synonyms
R-7010; PEGylated IGF1 (amyotrophic lateral sclerosis), Roche
    Click to Show/Hide
MOA Modulator
External Link
TTD: D03WNN
 Compound Name HF-0299 Phase 1 [16]
MOA Modulator
External Link
TTD: D0L1ZM
 Compound Name BIIB 022 Phase 1 [17]
MOA Antagonist
External Link
TTD: D0O7QQ
 Compound Name FPI-1434 Phase 1 [18]
External Link
TTD: D4JYH3
 Compound Name AEW-541 Phase 1 [19]
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]-
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MOA Inhibitor
Activity IC50 = 60 nM
External Link
CID: 11476171
TTD: D07HPJ
 Compound Name SAR446159 Phase 1 [20]
External Link
TTD: D10KTZ
 Compound Name AVE-1642 Discontinued in Phase 2 [21]
Synonyms
EM-164; Anti-IGF-1 receptor antibody (cancer), Aventis; Anti-IGF-1 receptor antibody (cancer), ImmunoGen; Anti-insulin-like growth factor-1 receptor antibody, Aventis; Anti-insulin-like growth factor-1 receptor antibody, ImmunoGen; Anti-IGF-1 receptor antibody (cancer), sanofi-aventis; Anti-insulin-like growthfactor-1 receptor antibody, sanofi-aventis
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External Link
TTD: D00BPE
 Compound Name KW-2450 Discontinued in Phase 1/2 [22]
MOA Modulator
External Link
CID: 56847547
TTD: D0M3OR
 Compound Name Figitumumab Discontinued in Phase 1 [23]
Synonyms
AC1OCENC; (2R)-3-[(4S,6R,7R,10S)-4-[(E,2R)-4-[(2S,2'S,4R,4aS,6R,8aR)-4-hydroxy-2-[(1S,3S)-1-hydroxy-3-[(6S,9R,10S)-9-methyl-5,11-dioxaspiro[5.5]undecan-10-yl]butyl]-3-methylidenespiro[4a,7,8,8a-tetrahydro-4H-pyrano[3,2-b]pyran-6,5'-oxolane]-2'-yl]but-3-en-2-yl]-7-hydroxy-2-methyl-5,11-dioxaspiro[5.5]undec-1-en-10-yl]-2-hydroxy-2-methylpropanoic acid
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MOA Inhibitor
External Link
TTD: D0U6KH
 Compound Name BMS-695735 Preclinical [24]
MOA Inhibitor
Activity IC50 = 34 nM
External Link
CID: 135441202
TTD: D0LF0O
 Compound Name EGFR/IGFR tandem adnectin Preclinical [25]
Synonyms
BMS-964210
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MOA Inhibitor
External Link
TTD: D0TI4U
 Compound Name NVP-ADW742 Investigative [26]
Synonyms
475488-23-4; ADW-742; 475489-15-7; UNII-MXS2N5862L; ADW742; MXS2N5862L; CHEMBL399021; 5-(3-(Benzyloxy)phenyl)-7-((1r,3r)-3-(pyrrolidin-1-ylmethyl)-cyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine; 5-(3-(Benzyloxy)phenyl)-7-(cis-3-(pyrrolidin-1-ylmethyl)cyclobutyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine; C28H31N5O; 5-(3-Benzyloxyphenyl)-7-[trans-3-[(pyrrolidin-1-yl)methyl]cyclobutyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine
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MOA Inhibitor
Activity IC50 = 323 nM
External Link
CID: 9825149
TTD: D06NMZ
 Compound Name JB-1 Investigative [26]
Synonyms
JB1
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MOA Inhibitor
External Link
CID: 25150849
TTD: D0O0RY
 Compound Name 4-((naphthalen-2-ylamino)methyl)benzene-1,2-diol Investigative [27]
Synonyms
CHEMBL1240677; BDBM50326006
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MOA Inhibitor
Activity IC50 = 4500 nM
External Link
CID: 43680262
TTD: D0L7MM
 Compound Name 4-((1H-indazol-6-ylamino)methyl)benzene-1,2-diol Investigative [27]
Synonyms
CHEMBL1240676; BDBM50326004
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MOA Inhibitor
Activity IC50 = 1500 nM
External Link
CID: 43743432
TTD: D0W9KO
 Compound Name AMP-PNP Investigative [28]
Synonyms
Phosphoaminophosphonic acid-adenylate ester; gamma-Imino-ATP; ADENYLYL IMIDODIPHOSPHATE; AMPPNP; Adenyl imidodiphosphate; 25612-73-1; adenyl-5'-yl imidodiphosphate; CHEBI:47785; App(NH)p; O(5')-(1,2-dihydroxy-2-phosphonoaminodiphosphoryl)adenosine; 5'-O-(hydroxy{[hydroxy(phosphonoamino)phosphoryl]oxy}phosphoryl)adenosine; [[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]amino]phosphonic acid; p(NH)Ppf; beta,gamma-Imido-ATP; beta,gamma-Imidoadenosine
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MOA Inhibitor
External Link
CID: 33113
TTD: D00ICA
 Compound Name BMS-536924 Investigative [29]
MOA Inhibitor
Activity IC50 = 100 nM
External Link
CID: 135440466
TTD: D0M4SY
 Compound Name Fucose Investigative [30]
Synonyms
L-galactomethylose; 6-Desoxygalactose; SCHEMBL13092958; AKOS030212707
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MOA Inhibitor
External Link
CID: 17106
TTD: D0G6XS
 Compound Name Alpha-D-Mannose Investigative [30]
Synonyms
alpha-D-Mannopyranose; alpha-Mannose; alpha-D-Man; UNII-W3F28J9G0W; CHEBI:28729; 7296-15-3; W3F28J9G0W; 3h-mannose; Manalpha1,; 1rdl; 1rin; 29696-75-1; Epitope ID:130701; AC1Q59RC; AC1L4HD7; SCHEMBL76882; CHEMBL365590; WQZGKKKJIJFFOK-PQMKYFCFSA-N; ZINC3860903; FT-0773891; C00936; WURCS=2.0/1,1,0/[a1122h-1a_1-5]/1/
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MOA Inhibitor
External Link
CID: 185698
TTD: D07LUR
 Compound Name ATL-1101 Preclinical [31]
External Link
TTD: D01QKD
 Compound Name AG 1024 Investigative [31]
Synonyms
tyrphostin AG 1024; AG-1024; AG1024
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External Link
CID: 2044
TTD: D01ODR
 Compound Name PQ401 Investigative [31]
Synonyms
PQ 401; IGF-1R inhibitor II; PQ-401
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Activity IC50 < 1000 nM
External Link
CID: 9549305
TTD: D0B4SU
 Compound Name GSK1511931 Investigative [31]
Synonyms
GSK1511931A; GSK-1511931; compound 14 [PMID: 19081716]
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Activity IC50 = 250 nM
External Link
CID: 44581765
TTD: D0E4LC
 Compound Name AZD3463 Investigative [31]
Synonyms
AZD-3463; CS-1382; HY-15609; KB-154896
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External Link
CID: 56599293
TTD: D0O7LU
 Compound Name GSK-1838705A Investigative [31]
Synonyms
GSK 1838705A; GSK1838705A
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Activity IC50 = 2 nM
External Link
CID: 25182616
TTD: D06PJW
References
Ref 1 DRAIC mediates hnRNPA2B1 stability and m(6)A-modified IGF1R instability to inhibit tumor progression. Oncogene. 2024 Jul;43(29):2266-2278. doi: 10.1038/s41388-024-03071-8. Epub 2024 May 29.
Ref 2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
Ref 3 IGF-1R, IGF-1 and IGF-2 expression as potential prognostic and predictive markers in colorectal-cancer. Virchows Arch. 2003 Aug;443(2):139-45. doi: 10.1007/s00428-003-0856-5. Epub 2003 Jul 5.
Ref 4 2005 approvals: Safety first. Nature Reviews Drug Discovery 5, 92-93 (February 2006).
Ref 5 Imidazo[2,1-b]thiazoles: multitargeted inhibitors of both the insulin-like growth factor receptor and members of the epidermal growth factor family... Bioorg Med Chem Lett. 2010 Apr 15;20(8):2452-5.
Ref 6 Mecasermin rinfabate: insulin-like growth factor-I/insulin-like growth factor binding protein-3, mecaserimin rinfibate, rhIGF-I/rhIGFBP-3. Drugs R D. 2005;6(2):120-7. doi: 10.2165/00126839-200506020-00008.
Ref 7 Clinical pipeline report, company report or official report of Amgen (2009).
Ref 8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 9 Clinical Phase I study with an Insulin-like Growth Factor-1 receptor inhibitor: experiences in patients with squamous non-small cell lung carcinoma. Acta Oncol. 2011 Apr;50(3):441-7. doi: 10.3109/0284186X.2010.499370. Epub 2010 Aug 11.
Ref 10 Clinical pipeline report, company report or official report of Roche (2009).
Ref 11 Doxorubicin plus the IGF-1R antibody cixutumumab in soft tissue sarcoma: a phase I study using the TITE-CRM model. Ann Oncol. 2015 Jul;26(7):1459-64. doi: 10.1093/annonc/mdv171. Epub 2015 Apr 9.
Ref 12 BiPar Sciences Co-founder Reunites Management Team At TriAct Therapeutics to Advance Clinical Stage Cancer Programs. TriAct Therapeutics. Sept. 10, 2009.
Ref 13 MM-141, an IGF-IR- and ErbB3-directed bispecific antibody, overcomes network adaptations that limit activity of IGF-IR inhibitors. Mol Cancer Ther. 2014 Feb;13(2):410-25. doi: 10.1158/1535-7163.MCT-13-0255. Epub 2013 Nov 26.
Ref 14 The cyclolignan picropodophyllin attenuates intimal hyperplasia after rat carotid balloon injury by blocking insulin-like growth factor-1 receptor signaling. J Vasc Surg. 2007 Jul;46(1):108-15. doi: 10.1016/j.jvs.2007.02.066.
Ref 15 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031207)
Ref 16 A primary adrenal steroid, 11beta-hydroxyandrostenedione, has an osteotropic effect and little androgenic activity. J Steroid Biochem Mol Biol. 2000 Nov 15;74(4):203-11. doi: 10.1016/s0960-0760(00)00124-2.
Ref 17 A phase 1, open-label, dose-escalation study of BIIB022 (anti-IGF-1R monoclonal antibody) in subjects with relapsed or refractory solid tumors. Invest New Drugs. 2014 Jun;32(3):518-25. doi: 10.1007/s10637-014-0064-y. Epub 2014 Jan 24.
Ref 18 Clinical pipeline report, company report or official report of Fusion Pharmaceuticals.
Ref 19 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
Ref 20 Clinical pipeline report, company report or official report of Sanofi
Ref 21 Insulin-like growth factor-1 receptor inhibition induces a resistance mechanism via the epidermal growth factor receptor/HER3/AKT signaling pathway: rational basis for cotargeting insulin-like growth factor-1 receptor and epidermal growth factor receptor in hepatocellular carcinoma. Clin Cancer Res. 2009 Sep 1;15(17):5445-56. doi: 10.1158/1078-0432.CCR-08-2980. Epub 2009 Aug 25.
Ref 22 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 23 Pfizer. Product Development Pipeline. March 31 2009.
Ref 24 Discovery and evaluation of 4-(2-(4-chloro-1H-pyrazol-1-yl)ethylamino)-3-(6-(1-(3-fluoropropyl)piperidin-4-yl)-4-methyl-1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one (BMS-695735), an orally efficacious inhibitor of insulin-like growth factor-1 receptor kinase with broad spectrum in vivo antitumor activity. J Med Chem. 2008 Oct 9;51(19):5897-900. doi: 10.1021/jm800832q. Epub 2008 Sep 3.
Ref 25 Clinical pipeline report, company report or official report of Bristol-Myers Squibb.
Ref 26 Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127. doi: 10.1517/14728210802676278.
Ref 27 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 28 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. doi: 10.1093/nar/28.1.235.
Ref 29 SAR of PXR transactivation in benzimidazole-based IGF-1R kinase inhibitors. Bioorg Med Chem Lett. 2010 Mar 1;20(5):1744-8. doi: 10.1016/j.bmcl.2010.01.087. Epub 2010 Jan 21.
Ref 30 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 31 TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751.