Details of the Drug

General Information of Drug (ID: DMTNQB0)

Drug Name

CC-486

Synonyms

AG-14361; AG14361; 328543-09-5; UNII-48N0U0K50I; AG 14361; CHEMBL65892; 48N0U0K50I; Imidazo[4,5,1-jk][1,4]benzodiazepin-7(4H)-one, 2-[4-[(dimethylamino)methyl]phenyl]-5,6-dihydro-; AG-014361; 1-(4-((dimethylamino)methyl)phenyl)-8,9-dihydro-2,7,9a-triazabenzo[cd]azulen-6(7H)-one; Imidazo(4,5,1-jk)(1,4)benzodiazepin-7(4H)-one, 2-(4-((dimethylamino)methyl)phenyl)-5,6-dihydro-; 2-[4-[(Dimethylamino)methyl]phenyl]-5,6-dihydroimidazo[4,5,1-jk][1,4]benzodiazepin-7(4H)-one; SMR000486393; MLS006011157; MLS001065917; Nucleoside analogue

Indication

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Phase 3	[1]
Myelodysplastic syndrome	2A37	Phase 3	[2]
Diffuse large B-cell lymphoma	2A81	Phase 1	[1]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

320.4

Topological Polar Surface Area (xlogp)

1.9

Rotatable Bond Count (rotbonds)

3

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

3

Chemical Identifiers

Formula: C19H20N4O
IUPAC Name: 2-[4-[(dimethylamino)methyl]phenyl]-1,3,10-triazatricyclo[6.4.1.04,13]trideca-2,4,6,8(13)-tetraen-9-one
Canonical SMILES: CN(C)CC1=CC=C(C=C1)C2=NC3=CC=CC4=C3N2CCNC4=O
InChI: InChI=1S/C19H20N4O/c1-22(2)12-13-6-8-14(9-7-13)18-21-16-5-3-4-15-17(16)23(18)11-10-20-19(15)24/h3-9H,10-12H2,1-2H3,(H,20,24)
InChIKey: SEKJSSBJKFLZIT-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 9840076
ChEBI ID: CHEBI:92015
CAS Number: 328543-09-5
TTD ID: D09NTC

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
DNA [cytosine-5]-methyltransferase 1 (DNMT1)	TT6S2FE	DNMT1_HUMAN	Inhibitor	[3]
Poly [ADP-ribose] polymerase 1 (PARP1)	TTVDSZ0	PARP1_HUMAN	Inhibitor	[4]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Acute myeloid leukaemia

ICD Disease Classification

2A60

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Poly [ADP-ribose] polymerase 1 (PARP1)	DTT	PARP1	1.62E-122	0.77	3
DNA [cytosine-5]-methyltransferase 1 (DNMT1)	DTT	DNMT1	1.56E-81	0.73	2.22

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2	J Clin Oncol 33, 2015 (suppl, abstr TPS7097).
3	Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes. Leukemia. 2016 Apr;30(4):889-96.
4	Tricyclic benzimidazoles as potent poly(ADP-ribose) polymerase-1 inhibitors. J Med Chem. 2003 Jan 16;46(2):210-3.
5	beta-1,2,3-Triazolyl-nucleosides as nicotinamide riboside mimics. Nucleosides Nucleotides Nucleic Acids. 2009 Mar;28(3):238-59.
6	Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3. J Med Chem. 2009 May 14;52(9):3108-11.
7	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
8	Inhibition of poly (ADP-ribose) polymerase as a protective effect of nicaraven in ionizing radiation- and ara-C-induced cell death. Anticancer Res. 2006 Sep-Oct;26(5A):3421-7.
9	PARP inhibitors as antitumor agents: a patent update (2013-2015).Expert Opin Ther Pat. 2017 Mar;27(3):363-382.
10	Clinical pipeline report, company report or official report of Allarity Therapeutics.
11	Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors. Nat Rev Drug Discov. 2005 May;4(5):421-40.
12	AMXI-5001, a novel dual parp1/2 and microtubule polymerization inhibitor for the treatment of human cancers. Am J Cancer Res. 2020 Aug 1;10(8):2649-2676.
13	NMS-P293, a PARP-1 selective inhibitor with no trapping activity and high CNS penetration, possesses potent in vivo efficacy and represents a novel therapeutic option for brain localized metastases and glioblastoma. Cancer Res 2018;78(13 Suppl):Abstract nr 4843.
14	S110, a 5-Aza-2'-deoxycytidine-containing dinucleotide, is an effective DNA methylation inhibitor in vivo and can reduce tumor growth. Mol Cancer Ther. 2010 May;9(5):1443-50.
15	Immunomodulatory action of the DNA methyltransferase inhibitor SGI-110 in epithelial ovarian cancer cells and xenografts. Epigenetics. 2015;10(3):237-46.
16	Anticancer activity of stabilized palifosfamide in vivo: schedule effects, oral bioavailability, and enhanced activity with docetaxel and doxorubicin. Anticancer Drugs. 2012 Feb;23(2):173-84.
17	Metabolism, mechanism of action and sensitivity profile of fluorocyclopentenylcytosine (RX-3117; TV-1360). Invest New Drugs. 2013 Dec;31(6):1444-57.
18	Antroquinonol D, isolated from Antrodia camphorata, with DNA demethylation and anticancer potential. J Agric Food Chem. 2014 Jun 18;62(24):5625-35.
19	DNA methyltransferase inhibitors: an updated patent review (2012-2015).Expert Opin Ther Pat. 2016 Sep;26(9):1017-30.