m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG02897)
Name
LY3039478
Synonyms
LY3039478; Crenigacestat; 1421438-81-4; LY-3039478; UNII-923X28214S; 4,4,4-Trifluoro-N-((S)-1-(((S)-5-(2-hydroxyethyl)-6-oxo-6,7-dihydro-5H-benzo[d]pyrido[2,3-b]azepin-7-yl)amino)-1-oxopropan-2-yl)butanamide; 923X28214S; butanamide, n-[(1s)-2-[[(7s)-6,7-dihydro-5-(2-hydroxyethyl)-6-oxo-5h-pyrido[3,2-a][3]benzazepin-7-yl]amino]-1-methyl-2-oxoethyl]-4,4,4-trifluoro-; Butanamide, N-((1S)-2-(((7S)-6,7-dihydro-5-(2-hydroxyethyl)-6-oxo-5H-pyrido(3,2-a)(3)benzazepin-7-yl)amino)-1-methyl-2-oxoethyl)-4,4,4-trifluoro-
    Click to Show/Hide
Status
Phase 1/2
Structure
Formula
C22H23F3N4O4
InChI
1S/C22H23F3N4O4/c1-13(27-17(31)8-9-22(23,24)25)20(32)28-18-15-6-3-2-5-14(15)16-7-4-10-26-19(16)29(11-12-30)21(18)33/h2-7,10,13,18,30H,8-9,11-12H2,1H3,(H,27,31)(H,28,32)/t13-,18-/m0/s1
InChIKey
YCBAQKQAINQRFW-UGSOOPFHSA-N
PubChem CID
71236992
TTD Drug ID
D08WOW
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.
Notch-1 receptor (NOTCH1)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Notch-1 receptor (NOTCH1) is a therapeutic target for LY3039478. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of LY3039478 through regulating the expression of Notch-1 receptor (NOTCH1). [1], [2]
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Notch-1 receptor (NOTCH1) is a therapeutic target for LY3039478. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of LY3039478 through regulating the expression of Notch-1 receptor (NOTCH1). [2], [3]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Notch-1 receptor (NOTCH1) is a therapeutic target for LY3039478. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of LY3039478 through regulating the expression of Notch-1 receptor (NOTCH1). [2], [4]
YTH domain-containing family protein 2 (YTHDF2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Notch-1 receptor (NOTCH1) is a therapeutic target for LY3039478. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of LY3039478 through regulating the expression of Notch-1 receptor (NOTCH1). [2], [5]
Notch-4 receptor (NOTCH4)
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Notch-4 receptor (NOTCH4) is a therapeutic target for LY3039478. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of LY3039478 through regulating the expression of Notch-4 receptor (NOTCH4). [6], [7]
References
Ref 1 The tumor-suppressive effects of alpha-ketoglutarate-dependent dioxygenase FTO via N6-methyladenosine RNA methylation on bladder cancer patients. Bioengineered. 2021 Dec;12(1):5323-5333. doi: 10.1080/21655979.2021.1964893.
Ref 2 EIAV-based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1B: development of UshStat. PLoS One. 2014 Apr 4;9(4):e94272. doi: 10.1371/journal.pone.0094272. eCollection 2014.
Ref 3 Mettl14 inhibits bladder TIC self-renewal and bladder tumorigenesis through N(6)-methyladenosine of Notch1. Mol Cancer. 2019 Nov 25;18(1):168. doi: 10.1186/s12943-019-1084-1.
Ref 4 METTL3-mediated m(6)A mRNA modification promotes esophageal cancer initiation and progression via Notch signaling pathway. Mol Ther Nucleic Acids. 2021 Jul 21;26:333-346. doi: 10.1016/j.omtn.2021.07.007. eCollection 2021 Dec 3.
Ref 5 YTHDF2 Suppresses Notch Signaling through Post-transcriptional Regulation on Notch1. Int J Biol Sci. 2021 Aug 28;17(14):3776-3785. doi: 10.7150/ijbs.61573. eCollection 2021.
Ref 6 N?-Methyladenosine Landscape of Glioma Stem-Like Cells: METTL3 Is Essential for the Expression of Actively Transcribed Genes and Sustenance of the Oncogenic Signaling. Genes (Basel). 2019 Feb 13;10(2):141. doi: 10.3390/genes10020141.
Ref 7 Discovery of novel CDK1 inhibitors by combining pharmacophore modeling, QSAR analysis and in silico screening followed by in vitro bioassay. Eur J Med Chem. 2010 Sep;45(9):4316-30. doi: 10.1016/j.ejmech.2010.06.034. Epub 2010 Jun 30.