General Information of the Drug (ID: M6ADRUG0064)
Name
Asparagine inhibitor
Synonyms
Agedoite; Altheine; Crystal VI
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Status Approved [1]
Structure
Formula
C4H8N2O3
InChI
InChI=1S/C4H8N2O3/c5-2(4(8)9)1-3(6)7/h2H,1,5H2,(H2,6,7)(H,8,9)/t2-/m0/s1
InChIKey
DCXYFEDJOCDNAF-REOHCLBHSA-N
PubChem CID
6267
TTD Drug ID
D03MYY
DrugBank ID
DB00174
Full List of m6A Targets Related to This Drug
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.
Responsed Disease Colorectal cancer ICD-11: 2B91
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
Target Regulation Down regulation
Pathway Response mTOR signaling pathway hsa04150
Cell Process RNA decay
Cell growth and death
Cell autophagy
In-vitro Model HCT 116 Colon carcinoma Homo sapiens CVCL_0291
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.
Responsed Disease Colorectal cancer ICD-11: 2B91
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Pathway Response mTOR signaling pathway hsa04150
Cell Process RNA decay
Cell growth and death
Cell autophagy
In-vitro Model HCT 116 Colon carcinoma Homo sapiens CVCL_0291
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
Serine/threonine-protein kinase mTOR (MTOR)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.
Responsed Disease Colorectal cancer ICD-11: 2B91
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
Target Regulation Up regulation
Pathway Response mTOR signaling pathway hsa04150
Autophagy hsa04140
Cell Process RNA decay
Cell growth and death
Cell autophagy
In-vitro Model HCT 116 Colon carcinoma Homo sapiens CVCL_0291
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.
Responsed Disease Colorectal cancer ICD-11: 2B91
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Pathway Response mTOR signaling pathway hsa04150
Autophagy hsa04140
Cell Process RNA decay
Cell growth and death
Cell autophagy
In-vitro Model HCT 116 Colon carcinoma Homo sapiens CVCL_0291
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
References
Ref 1 Structural and biochemical properties of L-asparaginase. FEBS J. 2021 Jul;288(14):4183-4209. doi: 10.1111/febs.16042. Epub 2021 Jun 19.
Ref 2 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.