General Information of the Drug (ID: M6APDG01196)
Name
PP121
Synonyms
PP-121; PP 121
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Status
Investigative
Structure
Formula
C17H17N7
InChI
1S/C17H17N7/c18-15-13-14(11-7-10-5-6-19-16(10)20-8-11)23-24(12-3-1-2-4-12)17(13)22-9-21-15/h5-9,12H,1-4H2,(H,19,20)(H2,18,21,22)
InChIKey
NVRXTLZYXZNATH-UHFFFAOYSA-N
PubChem CID
24905142
TTD Drug ID
D03EHM
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 PP121. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of PP121 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 PP121. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of PP121 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 PP121. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of PP121 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 PP121. The YTH domain-containing family protein 1 (YTHDF1) has potential in affecting the response of PP121 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 PP121. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of PP121 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 PP121. The YTH domain-containing family protein 3 (YTHDF3) has potential in affecting the response of PP121 through regulating the expression of Epidermal growth factor receptor (EGFR). [2], [7]
PI3-kinase beta (PIK3CB)
Methyltransferase-like 13 (METTL13)
In total 1 mechanisms lead to this potential drug response
Response Summary PI3-kinase beta (PIK3CB) is a therapeutic target for PP121. The Methyltransferase-like 13 (METTL13) has potential in affecting the response of PP121 through regulating the expression of PI3-kinase beta (PIK3CB). [8], [9]
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
Response Summary PI3-kinase beta (PIK3CB) is a therapeutic target for PP121. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of PP121 through regulating the expression of PI3-kinase beta (PIK3CB). [8], [9]
Wilms tumor 1-associating protein (WTAP)
In total 1 mechanisms lead to this potential drug response
Response Summary PI3-kinase beta (PIK3CB) is a therapeutic target for PP121. The Wilms tumor 1-associating protein (WTAP) has potential in affecting the response of PP121 through regulating the expression of PI3-kinase beta (PIK3CB). [8], [9]
YTH domain-containing family protein 2 (YTHDF2)
In total 1 mechanisms lead to this potential drug response
Response Summary PI3-kinase beta (PIK3CB) is a therapeutic target for PP121. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of PP121 through regulating the expression of PI3-kinase beta (PIK3CB). [8], [9]
Platelet-derived growth factor receptor alpha (PDGFRA)
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
Response Summary Platelet-derived growth factor receptor alpha (PDGFRA) is a therapeutic target for PP121. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of PP121 through regulating the expression of Platelet-derived growth factor receptor alpha (PDGFRA). [10], [11]
Serine/threonine-protein kinase mTOR (mTOR)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
Response Summary Serine/threonine-protein kinase mTOR (mTOR) is a therapeutic target for PP121. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of PP121 through regulating the expression of Serine/threonine-protein kinase mTOR (mTOR). [12], [13]
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
Response Summary Serine/threonine-protein kinase mTOR (mTOR) is a therapeutic target for PP121. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of PP121 through regulating the expression of Serine/threonine-protein kinase mTOR (mTOR). [13], [14]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
Response Summary Serine/threonine-protein kinase mTOR (mTOR) is a therapeutic target for PP121. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of PP121 through regulating the expression of Serine/threonine-protein kinase mTOR (mTOR). [13], [15]
YTH domain-containing family protein 1 (YTHDF1)
In total 1 mechanisms lead to this potential drug response
Response Summary Serine/threonine-protein kinase mTOR (mTOR) is a therapeutic target for PP121. The YTH domain-containing family protein 1 (YTHDF1) has potential in affecting the response of PP121 through regulating the expression of Serine/threonine-protein kinase mTOR (mTOR). [13], [16]
YTH domain-containing family protein 2 (YTHDF2)
In total 1 mechanisms lead to this potential drug response
Response Summary Serine/threonine-protein kinase mTOR (mTOR) is a therapeutic target for PP121. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of PP121 through regulating the expression of Serine/threonine-protein kinase mTOR (mTOR). [12], [13]
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 Tyrosine kinase inhibitors. 8. An unusually steep structure-activity relationship for analogues of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a potent inhibitor of the epidermal growth factor receptor. J Med Chem. 1996 Jan 5;39(1):267-76. doi: 10.1021/jm9503613.
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 N(6)-methyladenosine mRNA methylation of PIK3CB regulates AKT signalling to promote PTEN-deficient pancreatic cancer progression. Gut. 2020 Dec;69(12):2180-2192. doi: 10.1136/gutjnl-2019-320179. Epub 2020 Apr 20.
Ref 9 Human target validation of phosphoinositide 3-kinase (PI3K)beta: effects on platelets and insulin sensitivity, using AZD6482 a novel PI3Kbeta inhibitor. J Thromb Haemost. 2012 Oct;10(10):2127-36.
Ref 10 METTL3-mediated N (6)-methyladenosine modification governs pericyte dysfunction during diabetes-induced retinal vascular complication. Theranostics. 2022 Jan 1;12(1):277-289. doi: 10.7150/thno.63441. eCollection 2022.
Ref 11 Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3743-8. doi: 10.1016/j.bmcl.2011.04.060. Epub 2011 Apr 22.
Ref 12 Targeting ATF4-dependent pro-survival autophagy to synergize glutaminolysis inhibition. Theranostics. 2021 Jul 25;11(17):8464-8479. doi: 10.7150/thno.60028. eCollection 2021.
Ref 13 Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9. doi: 10.1038/nchembio.117. Epub 2008 Oct 12.
Ref 14 The m6A methyltransferase METTL14 inhibits the proliferation, migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway. J Clin Lab Anal. 2021 Mar;35(3):e23655. doi: 10.1002/jcla.23655. Epub 2020 Dec 12.
Ref 15 Methyltransferase-like 3 promotes the progression of lung cancer via activating PI3K/AKT/mTOR pathway. Clin Exp Pharmacol Physiol. 2022 Jul;49(7):748-758. doi: 10.1111/1440-1681.13647. Epub 2022 May 23.
Ref 16 YTHDF1 promotes hepatocellular carcinoma progression via activating PI3K/AKT/mTOR signaling pathway and inducing epithelial-mesenchymal transition. Exp Hematol Oncol. 2021 Jun 4;10(1):35. doi: 10.1186/s40164-021-00227-0.