m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG04148)
Name
TT-100
Synonyms
TT-100, TriAct; Dual IGF-1/EGFR inhibitor (non-small-cell lung cancer), TriAct
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Status
Phase 2
TTD Drug ID
D0T5JS
Target Gene(s) and Their Upstream m6A Regulator, Together with the Effect of Target Gene(s) in Drug Response
The target genes involved in drug-target interaction (such as drug-metabolizing enzymes, drug transporters and therapeutic targets) and drug-mediated cell death signaling (including modulating DNA damage and repair capacity, escaping from drug-induced apoptosis, autophagy, cellular metabolic reprogramming, oncogenic bypass signaling, cell microenvironment, cell stemness, etc.) could be regulated by m6A regulator(s) and affected their corresponding drug response. You can browse detailed information on drug-related target gene(s) mediated by m6A regulators.
Epidermal growth factor receptor (EGFR)
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for TT-100. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of TT-100 through regulating the expression of Epidermal growth factor receptor (EGFR). [1], [2]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for TT-100. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of TT-100 through regulating the expression of Epidermal growth factor receptor (EGFR). [2], [3]
RNA demethylase ALKBH5 (ALKBH5)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for TT-100. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of TT-100 through regulating the expression of Epidermal growth factor receptor (EGFR). [2], [4]
YTH domain-containing family protein 1 (YTHDF1)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for TT-100. The YTH domain-containing family protein 1 (YTHDF1) has potential in affecting the response of TT-100 through regulating the expression of Epidermal growth factor receptor (EGFR). [2], [5]
YTH domain-containing family protein 2 (YTHDF2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for TT-100. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of TT-100 through regulating the expression of Epidermal growth factor receptor (EGFR). [2], [6]
YTH domain-containing family protein 3 (YTHDF3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for TT-100. The YTH domain-containing family protein 3 (YTHDF3) has potential in affecting the response of TT-100 through regulating the expression of Epidermal growth factor receptor (EGFR). [2], [7]
Insulin-like growth factor I receptor (IGF1R)
Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Insulin-like growth factor I receptor (IGF1R) is a therapeutic target for TT-100. The Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has potential in affecting the response of TT-100 through regulating the expression of Insulin-like growth factor I receptor (IGF1R). [8], [9]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Insulin-like growth factor I receptor (IGF1R) is a therapeutic target for TT-100. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of TT-100 through regulating the expression of Insulin-like growth factor I receptor (IGF1R). [9], [10]
RNA demethylase ALKBH5 (ALKBH5)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Insulin-like growth factor I receptor (IGF1R) is a therapeutic target for TT-100. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of TT-100 through regulating the expression of Insulin-like growth factor I receptor (IGF1R). [9], [11]
YTH domain-containing protein 2 (YTHDC2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Insulin-like growth factor I receptor (IGF1R) is a therapeutic target for TT-100. The YTH domain-containing protein 2 (YTHDC2) has potential in affecting the response of TT-100 through regulating the expression of Insulin-like growth factor I receptor (IGF1R). [9], [12]
References
Ref 1 METTL14 Inhibits Hepatocellular Carcinoma Metastasis Through Regulating EGFR/PI3K/AKT Signaling Pathway in an m6A-Dependent Manner. Cancer Manag Res. 2020 Dec 23;12:13173-13184. doi: 10.2147/CMAR.S286275. eCollection 2020.
Ref 2 Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab. Cancer Biol Ther. 2011 May 1;11(9):777-92. doi: 10.4161/cbt.11.9.15050. Epub 2011 May 1.
Ref 3 METTL3 induces PLX4032 resistance in melanoma by promoting m(6)A-dependent EGFR translation. Cancer Lett. 2021 Dec 1;522:44-56. doi: 10.1016/j.canlet.2021.09.015. Epub 2021 Sep 13.
Ref 4 ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2. J Exp Clin Cancer Res. 2019 Apr 15;38(1):163. doi: 10.1186/s13046-019-1159-2.
Ref 5 Insufficient Radiofrequency Ablation Promotes Hepatocellular Carcinoma Metastasis Through N6-Methyladenosine mRNA Methylation-Dependent Mechanism. Hepatology. 2021 Sep;74(3):1339-1356. doi: 10.1002/hep.31766.
Ref 6 YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in hepatocellular carcinoma. Cancer Lett. 2019 Feb 1;442:252-261. doi: 10.1016/j.canlet.2018.11.006. Epub 2018 Nov 10.
Ref 7 YTHDF3 Induces the Translation of m(6)A-Enriched Gene Transcripts to Promote Breast Cancer Brain Metastasis. Cancer Cell. 2020 Dec 14;38(6):857-871.e7. doi: 10.1016/j.ccell.2020.10.004. Epub 2020 Oct 29.
Ref 8 IGF2BP2 promotes gastric cancer progression by regulating the IGF1R-RhoA-ROCK signaling pathway. Cell Signal. 2022 Jun;94:110313. doi: 10.1016/j.cellsig.2022.110313. Epub 2022 Mar 16.
Ref 9 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 10 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 11 ALKBH5 regulates IGF1R expression to promote the Proliferation and Tumorigenicity of Endometrial Cancer. J Cancer. 2020 Jul 25;11(19):5612-5622. doi: 10.7150/jca.46097. eCollection 2020.
Ref 12 m(6)A Reader YTHDC2 Promotes Radiotherapy Resistance of Nasopharyngeal Carcinoma via Activating IGF1R/AKT/S6 Signaling Axis. Front Oncol. 2020 Jul 31;10:1166. doi: 10.3389/fonc.2020.01166. eCollection 2020.