Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM0214E)

• Drug Name: NSC-401077 Drug Info
• Synonyms: NSC401077; MLS000757170; DNA Methyltransferase Inhibitor; CHEMBL383475; NSC-401077; 32675-71-1; 2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-(1H-indol-3-yl)-propionic acid; 2-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)-3-(1H-indol-3-yl)propanoic acid; 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-(1H-indol-3-yl)propanoic acid; 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-(1H-indol-3-yl)propionic acid; SMR000413613; AC1Q71QA; Oprea1_475901; Oprea1_410805; MLS000777218; MLS006011919; SCHEMBL562060

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 344265
  CAS Number: CAS 32675-71-1
  TTD Drug ID: DM0214E

Molecule-Related Drug Atlas

Drug(s) Targeting DNA [cytosine-5]-methyltransferase 3B (DNMT3B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[1]
PMID27376512-Compound-MTC-424	DMGNRZU	N. A.	N. A.	Patented	[3]
PMID27376512-Compound-MTC-427	DMWXEZD	N. A.	N. A.	Patented	[3]
PMID27376512-Compound-MTC-422	DM1MVQD	N. A.	N. A.	Patented	[3]
PMID27376512-Compound-MTC-423	DM9RSDX	N. A.	N. A.	Patented	[3]
(L-)-S-adenosyl-L-homocysteine	DMDUN83	Discovery agent	N.A.	Investigative	[4]
NSC-622445	DME35CB	Discovery agent	N.A.	Investigative	[1]
NSC-622444	DMM5UT9	Discovery agent	N.A.	Investigative	[1]
NSC-138419	DMH684Q	Discovery agent	N.A.	Investigative	[1]
NSC-319745	DMF3G06	Discovery agent	N.A.	Investigative	[1]

Drug(s) Targeting DNA [cytosine-5]-methyltransferase (DNMT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Azacitidine	DMTA5OE	Acute myelogenous leukaemia	2A41	Approved	[5]
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[1]
S-110	DMXY34J	Acute myeloid leukaemia	2A60	Phase 3	[6]
ASTX727	DM4HK8Z	Chronic myelogenous leukaemia	2A20.0	Phase 3	[7]
PMID27376512-Compound-PG-11047	DM5K4YF	N. A.	N. A.	Patented	[3]
PMID27376512-Compound-PG-11048	DM3U7RN	N. A.	N. A.	Patented	[3]
PMID27376512-Compound-MTC-434	DM70CTE	N. A.	N. A.	Patented	[3]
PMID27376512-Compound-CROs	DMBFUTL	N. A.	N. A.	Patented	[3]
(L-)-S-adenosyl-L-homocysteine	DMDUN83	Discovery agent	N.A.	Investigative	[4]
NSC-622445	DME35CB	Discovery agent	N.A.	Investigative	[1]

Drug(s) Affected By DNA cytosine-5)-methyltransferase 1 (DNMT1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[8]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[9]
Cladribine	DM3JDRP	Hairy cell leukaemia	2A82.2	Approved	[10]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[11]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[12]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[13]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[14]
Acetic Acid, Glacial	DM4SJ5Y	infection in the ear canal	AA0Y	Approved	[15]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[16]
Hydroquinone	DM6AVR4	Melasma	ED60.1	Approved	[17]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
DNA [cytosine-5]-methyltransferase (DNMT)	TTHVCUP	NOUNIPROTAC	Inhibitor	[1]
DNA [cytosine-5]-methyltransferase 3B (DNMT3B)	TT6VZ78	DNM3B_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
DNA cytosine-5)-methyltransferase 1 (DNMT1)	OTM2DGTK	DNMT1_HUMAN	Gene/Protein Processing	[2]

References

• [1] Novel and selective DNA methyltransferase inhibitors: Docking-based virtual screening and experimental evaluation. Bioorg Med Chem. 2010 Jan 15;18(2):822-9.
• [2] Discovery of two novel, small-molecule inhibitors of DNA methylation. J Med Chem. 2006 Jan 26;49(2):678-83. doi: 10.1021/jm050844z.
• [3] DNA methyltransferase inhibitors: an updated patent review (2012-2015).Expert Opin Ther Pat. 2016 Sep;26(9):1017-30.
• [4] Constrained (l-)-S-adenosyl-l-homocysteine (SAH) analogues as DNA methyltransferase inhibitors. Bioorg Med Chem Lett. 2009 May 15;19(10):2742-6.
• [5] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid l... Leukemia. 2009 Jun;23(6):1019-28.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] mTOR inhibition reverses acquired endocrine therapy resistance of breast cancer cells at the cell proliferation and gene-expression levels. Cancer Sci. 2008 Oct;99(10):1992-2003. doi: 10.1111/j.1349-7006.2008.00955.x.
• [9] Oxidative stress-induced epigenetic changes associated with malignant transformation of human kidney epithelial cells. Oncotarget. 2017 Feb 14;8(7):11127-11143. doi: 10.18632/oncotarget.12091.
• [10] Comparative effects of retinoic acid, vitamin D and resveratrol alone and in combination with adenosine analogues on methylation and expression of phosphatase and tensin homologue tumour suppressor gene in breast cancer cells. Br J Nutr. 2012 Mar;107(6):781-90. doi: 10.1017/S0007114511003631. Epub 2011 Aug 1.
• [11] Multifaceted preventive effects of single agent quercetin on a human prostate adenocarcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy. Med Oncol. 2011 Dec;28(4):1395-404. doi: 10.1007/s12032-010-9603-3. Epub 2010 Jul 2.
• [12] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [13] The low-toxicity 9-cis UAB30 novel retinoid down-regulates the DNA methyltransferases and has anti-telomerase activity in human breast cancer cells. Int J Oncol. 2007 Mar;30(3):641-50.
• [14] Cyclophosphamide perturbs cytosine methylation in Jurkat-T cells through LSD1-mediated stabilization of DNMT1 protein. Chem Res Toxicol. 2011 Nov 21;24(11):2040-3. doi: 10.1021/tx2003849. Epub 2011 Nov 1.
• [15] DNA methyltransferase inhibitors coordinately induce expression of the human reelin and glutamic acid decarboxylase 67 genes. Mol Pharmacol. 2007 Mar;71(3):644-53. doi: 10.1124/mol.106.030635. Epub 2006 Oct 25.
• [16] Arsenic trioxide inhibits DNA methyltransferase and restores methylation-silenced genes in human liver cancer cells. Hum Pathol. 2006 Mar;37(3):298-311.
• [17] Hypomethylation mediated by decreased DNMTs involves in the activation of proto-oncogene MPL in TK6 cells treated with hydroquinone. Toxicol Lett. 2012 Mar 25;209(3):239-45. doi: 10.1016/j.toxlet.2011.12.020. Epub 2012 Jan 8.