General Information of the Drug (ID: M6APDG03972)
Name
MCLA-158
Status
Phase 1
TTD Drug ID
DV8I4Q
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
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for MCLA-158. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of MCLA-158 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
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for MCLA-158. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of MCLA-158 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
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for MCLA-158. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of MCLA-158 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
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for MCLA-158. The YTH domain-containing family protein 1 (YTHDF1) has potential in affecting the response of MCLA-158 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
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for MCLA-158. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of MCLA-158 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
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for MCLA-158. The YTH domain-containing family protein 3 (YTHDF3) has potential in affecting the response of MCLA-158 through regulating the expression of Epidermal growth factor receptor (EGFR). [2], [7]
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 Clinical pipeline report, company report or official report of Shionogi (2011).
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.