m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05294
 [1]
Non-coding RNA PCAT6 IGF2BP2  lncRNA       miRNA   circRNA Direct Enhancement m6A modification IGF1R IGF1R IGF2BP2 : m6A sites
m6A Modification:
m6A Regulator Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) 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 Prostate cancer associated transcript 6 (PCAT6) LncRNA View Details
Regulated Target Insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) View Details
Crosstalk Relationship ncRNA  →  m6A Enhancement
Crosstalk Mechanism ncRNAs directly impacts m6A modification through recruiting m6A regulator
Crosstalk Summary PCAT6 upregulated Insulin-like growth factor 1 receptor (IGF1R) expression by enhancing IGF1R mRNA stability through the PCAT6/IGF2BP2/IGF1R RNA-protein three-dimensional complex. Importantly, PCAT6 inhibition by ASO in vivo showed therapeutic potential against bone metastasis in PCa. Finally, the clinical correlation of METTL3, IGF2BP2, IGF1R, and PCAT6 was further demonstrated in PCa tissues and cells.
Responsed Disease Prostate cancer ICD-11: 2C82
 Disease Info 
Cell Process RNA stability
In-vivo Model For the animal model of BM, eight BALB/c-nu mice (male, 4-6 weeks old) in the indicated groups were injected with PC-3 cells (1 × 106) in 100 μl PBS into the left cardiac ventricle and further analyzed and measured by In Vivo Imaging System (IVIS, Caliper Life Sciences), X-ray, hematoxylin and eosin (H&E), and IHC staining.
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
    Click to Show/Hide
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
    Click to Show/Hide
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
    Click to Show/Hide
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
    Click to Show/Hide
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
    Click to Show/Hide
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]-
    Click to Show/Hide
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
    Click to Show/Hide
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
    Click to Show/Hide
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
    Click to Show/Hide
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
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 323 nM
External Link
CID: 9825149
TTD: D06NMZ
 Compound Name JB-1 Investigative [26]
Synonyms
JB1
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 25150849
TTD: D0O0RY
 Compound Name 4-((naphthalen-2-ylamino)methyl)benzene-1,2-diol Investigative [27]
Synonyms
CHEMBL1240677; BDBM50326006
    Click to Show/Hide
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
    Click to Show/Hide
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
    Click to Show/Hide
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
    Click to Show/Hide
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/
    Click to Show/Hide
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
    Click to Show/Hide
External Link
CID: 2044
TTD: D01ODR
 Compound Name PQ401 Investigative [31]
Synonyms
PQ 401; IGF-1R inhibitor II; PQ-401
    Click to Show/Hide
Activity IC50 < 1000 nM
External Link
CID: 9549305
TTD: D0B4SU
 Compound Name GSK1511931 Investigative [31]
Synonyms
GSK1511931A; GSK-1511931; compound 14 [PMID: 19081716]
    Click to Show/Hide
Activity IC50 = 250 nM
External Link
CID: 44581765
TTD: D0E4LC
 Compound Name AZD3463 Investigative [31]
Synonyms
AZD-3463; CS-1382; HY-15609; KB-154896
    Click to Show/Hide
External Link
CID: 56599293
TTD: D0O7LU
 Compound Name GSK-1838705A Investigative [31]
Synonyms
GSK 1838705A; GSK1838705A
    Click to Show/Hide
Activity IC50 = 2 nM
External Link
CID: 25182616
TTD: D06PJW
2C82: Prostate cancer 1 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name CC-94676 Phase 1 [32]
External Link
TTD: DNY63Z
References
Ref 1 m(6) A modification of lncRNA PCAT6 promotes bone metastasis in prostate cancer through IGF2BP2-mediated IGF1R mRNA stabilization. Clin Transl Med. 2021 Jun;11(6):e426. doi: 10.1002/ctm2.426.
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.
Ref 32 ClinicalTrials.gov (NCT04428788) Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CC-94676 in Subjects With Metastatic Castration-Resistant Prostate Cancer. U.S. National Institutes of Health.