m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03112
 [1]
m6A modification SETMAR SETMAR IGF2BP3 : m6A sites Direct Enhancement Histone modification H3K36me2 SETMAR SMARCA2
m6A Modification:
m6A Regulator Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) READER
 Regulator Info 
m6A Target Histone-lysine N-methyltransferase SETMAR (SETMAR)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone-lysine N-methyltransferase SETMAR (SETMAR) WRITER View Details
Regulated Target Histone H3 lysine 36 dimethylation (H3K36me2) View Details
Downstream Gene SMARCA2 View Details
Crosstalk Relationship m6A  →  Histone modification Enhancement
Crosstalk Mechanism m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes
Crosstalk Summary Mechanistically, Histone-lysine N-methyltransferase SETMAR (SETMAR) methylates Histone H3 lysine 36 dimethylation (H3K36me2) in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can increase H3K27Ac enrichment and bind to enhancers of the thyroid differentiation transcription factors (PAX8 and FOXE1) to promote their expression by enhancing chromatin accessibility. Moreover, METTL3-mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3-dependent manner.
Responsed Disease Thyroid Cancer ICD-11: 2D10
 Disease Info 
In-vitro Model
 CAL-62 Thyroid gland anaplastic carcinoma Homo sapiens CVCL_1112
C-643 Thyroid gland anaplastic carcinoma Homo sapiens CVCL_5969
B-CPAP Thyroid gland carcinoma Homo sapiens CVCL_0153
ACT-1 Thyroid gland anaplastic carcinoma Homo sapiens CVCL_6291
In-vivo Model 1 × 106 CAL-62 cells were subcutaneously injected into 6-week-old female BALB/c nude mice to establish tumor xenograft models.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
2D10: Thyroid Cancer 12 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Lenvatinib Approved [2]
Synonyms
E 7080; E-7080, E7080; 4-[3-chloro-4-(cyclopropylcarbamoylamino)phenoxy]-7-methoxy-quinoline-6-carboxamide
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CID: 9823820
TTD: D0R0FO
DrugBank: DB09078
 Compound Name Cabozantinib Approved [3]
Synonyms
Cabometyx; Cometriq
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CID: 25102847
TTD: D0IQ6P
DrugBank: DB08875
 Compound Name Thyrotropin Alfa Approved [4]
External Link
TTD: D0H4TQ
 Compound Name Selpercatinib Approved [5]
Synonyms
MFOVQWYFURMVKU-IWAAJCSBSA-N; 2222755-14-6; LOXO292; ARRY-192; LOXO 292; EX-A2636
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CID: 134823904
TTD: D01KOA
 Compound Name Selumetinib Phase 3 [6]
Synonyms
AZD-6244; ARRY142886; AZD6244; AZD 6244; 6UH91I579U; ARRY 142886; ARRY-142886; AZD6244 (Selumetinib); AZD6244(Selumetinib); CHEBI:90227; CHEMBL1614701; MEK inhibitors; Selumetinib (AZD6244); UNII-6UH91I579U
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CID: 10127622
TTD: D0T5DP
DrugBank: DB11689
 Compound Name QGE-031 Phase 2 [7]
External Link
TTD: D0J7CH
 Compound Name GI-6207 Phase 2 [8]
External Link
TTD: D0L7VC
 Compound Name AIC100 Phase 1 [9]
External Link
TTD: DP0NU9
 Compound Name CYTO-403 Phase 1 [10]
External Link
TTD: DB2R5Y
 Compound Name Demogastrin Phase 1 [11]
Synonyms
Technetium-99m-Demogastrin 2; Cholecystokinin-2 receptor/gastrin-R binding radiolabeled minigastrinanalogue (medullary thyroid cancer), Biomedica Life Science; 99mTc-Demogastrin 2; 99mTc-N4-Gly-(D)Glu-(Glu)5-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2
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TTD: D0QJ6L
 Compound Name Recombinant TSH superagonists Investigative [12]
Synonyms
Recombinant TSH superagonists (thyroid cancer); TR-1401; TR-1402; Recombinant TSH superagonists (thyroid cancer), Trophogen; TSH superagonist (thyroid cancer/goiter), Trophogen; Thyroid stimulating hormone superagonist (thyroid cancer/goiter), Trophogen
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TTD: D0U2DY
 Compound Name ITRI-305 Investigative [13]
Synonyms
RET tyrosine kinase inhibitors, Industrial Technology Research Institute
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TTD: D0N5TB
References
Ref 1 SETMAR Facilitates the Differentiation of Thyroid Cancer by Regulating SMARCA2-Mediated Chromatin Remodeling. Adv Sci (Weinh). 2024 Aug;11(32):e2401712. doi: 10.1002/advs.202401712. Epub 2024 Jun 20.
Ref 2 FDA Approved Drug Products from FDA Official Website. 2018. Application Number: (ANDA) 208627.
Ref 3 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. (Ligand id: 5887).
Ref 4 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020898.
Ref 5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
Ref 6 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 7 ClinicalTrials.gov (NCT02336425) Efficacy and Safety of QGE031 Compared With Placebo in Patients Aged 18-75 Years With Asthma. U.S. National Institutes of Health.
Ref 8 ClinicalTrials.gov (NCT01856920) A Phase 2 Study of GI-6207 in Patients With Recurrent Medullary Thyroid Cancer. U.S. National Institutes of Health.
Ref 9 ClinicalTrials.gov (NCT04420754) Study of AIC100 in Relapsed/Refractory Thyroid Cancer. U.S. National Institutes of Health.
Ref 10 Clinical pipeline report, company report or official report of Cytocom
Ref 11 99mTc-Demogastrin 2 for CCK 2-receptor scintigraphy in medullary thyroid carcinoma. J Nucl Med. 2008; 49 (Supplement 1):115P.
Ref 12 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: 255).
Ref 13 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: 2185).