Details of the Drug

General Information of Drug (ID: DMH7W9X)

Drug Name

SNDX-275

Synonyms

Entinostat; Histone Deacetylase Inhibitor I; IN1470; MS 275; SNDX 275; MS 27-275; Ms-275; Entinostat (USAN/INN); MS-27-275; Pyridin-3-ylmethyl 4-(2-aminophenylcarbamoyl)benzylcarbamate; Pyridin-3-ylmethyl N-[[4-[(2-aminophenyl)carbamoyl]phenyl]methyl]carbamate; Pyridin-3-ylmethyl {4-[(2-aminophenyl)carbamoyl]benzyl}carbamate; Pyridin-3-ylmethyl{4-[(2-aminophenyl)carbamoyl]benzyl}carbamate; Carbamic acid, [[4-[[(2-aminophenyl)amino]carbonyl]phenyl] methyl]-, 3-pyridinylmethyl ester; Carbamic acid, [[4-[[(2-aminophenyl)carbaonyl]phenyl]methyl]-, 3-pyridinylmethyl ester; Entinostat, SNDX-275, MS-27-275, MS-275; N-(2-Aminophenyl)-4-[N-(pyridin-3-yl-methoxycarbonyl)aminomethyl]benzamide; N-(2-aminophenyl)-4-(N-(pyridin-3-ylmethoxycarbonyl)aminomethyl)benzamide; Carbamic acid, ((4-(((2-aminophenyl)amino)carbonyl)phenyl)methyl)-, 3-pyridinylmethyl ester; 3-Pyridinylmethyl ((4-(((2-aminophenyl)amino)carbonyl)phenyl)methyl)carbamate

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 3	[1]
Colorectal cancer	2B91.Z	Phase 2	[2]
Melanoma	2C30	Phase 2	[2], [3]
Non-small-cell lung cancer	2C25.Y	Phase 2	[2]
Ovarian cancer	2C73	Phase 2	[2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

376.4

Topological Polar Surface Area (xlogp)

2

Rotatable Bond Count (rotbonds)

7

Hydrogen Bond Donor Count (hbonddonor)

3

Hydrogen Bond Acceptor Count (hbondacc)

5

Chemical Identifiers

Formula: C21H20N4O3
IUPAC Name: pyridin-3-ylmethyl N-[[4-[(2-aminophenyl)carbamoyl]phenyl]methyl]carbamate
Canonical SMILES: C1=CC=C(C(=C1)N)NC(=O)C2=CC=C(C=C2)CNC(=O)OCC3=CN=CC=C3
InChI: InChI=1S/C21H20N4O3/c22-18-5-1-2-6-19(18)25-20(26)17-9-7-15(8-10-17)13-24-21(27)28-14-16-4-3-11-23-12-16/h1-12H,13-14,22H2,(H,24,27)(H,25,26)
InChIKey: INVTYAOGFAGBOE-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 4261
ChEBI ID: CHEBI:132082
CAS Number: 209783-80-2
DrugBank ID: DB11841
TTD ID: D0M8FD
VARIDT ID: DR00732

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Histone deacetylase (HDAC)	TTBH0VX	NOUNIPROTAC	Inhibitor	[2], [3]
Histone deacetylase 1 (HDAC1)	TT6R7JZ	HDAC1_HUMAN	Inhibitor	[4]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Breast cancer

ICD Disease Classification

2C60-2C65

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Histone deacetylase 1 (HDAC1)	DTT	HDAC1	6.73E-02	0.24	0.59

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	ClinicalTrials.gov (NCT03538171) Ph3 Study of Exemestane With or Without Entinostat in Chinese Patients With Hormone Receptor-Positive, Locally Advanced or Metastatic Breast Cancer. U.S. National Institutes of Health.
2	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
5	Transcription-independent heritability of induced histone modifications in the mouse preimplantation embryo. PLoS One. 2009 Jun 30;4(6):e6086.
6	Histone Deacetylase inhibitors: new promise in the treatment of immune and inflammatory diseases. Curr Drug Targets. 2010 Nov;11(11):1430-8.
7	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
8	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8365).
9	US patent application no. 2012,0302,505, Cyclodextrin-based polymers for therapeutic delivery.
10	Phase 1 study of the oral histone deacetylase inhibitor abexinostat in patients with Hodgkin lymphoma, non-Hodgkin lymphoma, or chronic lymphocytic leukaemia. Invest New Drugs. 2015 Apr;33(2):423-31.
11	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
12	Protein methyltransferases as a target class for drug discovery. Nat Rev Drug Discov. 2009 Sep;8(9):724-32.
13	Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
14	Emerging drugs for the therapy of primary and post essential thrombocythemia, post polycythemia vera myelofibrosis. Expert Opin Emerg Drugs. 2009 Sep;14(3):471-9.
15	NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma. Blood. 2003 Oct 1;102(7):2615-22.
16	Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.
17	2011 Pipeline of 4SC AG.
18	Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov. 2006 Sep;5(9):769-84.