Details of the Drug

General Information of Drug (ID: DMFZBNE)

Drug Name
ITF2357
Synonyms Givinostat; Carbamic acid, N-(4-((hydroxyamino)carbonyl)phenyl)-, (6-((diethylamino)methyl)-2-naphthalenyl)methyl ester, hydrochloride (1:1)
Indication
Disease Entry ICD 11 Status REF
Duchenne dystrophy 8C70 Phase 3 [1]
Essential thrombocythemia 3B63.1Z Phase 2 [2], [3]
Myelofibrosis 2A20.2 Phase 2 [2], [3]
Polycythemia vera 2A20.4 Phase 2 [2], [3]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 421.5
Topological Polar Surface Area (xlogp) 3.6
Rotatable Bond Count (rotbonds) 9
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 5
Chemical Identifiers
Formula
C24H27N3O4
IUPAC Name
[6-(diethylaminomethyl)naphthalen-2-yl]methyl N-[4-(hydroxycarbamoyl)phenyl]carbamate
Canonical SMILES
CCN(CC)CC1=CC2=C(C=C1)C=C(C=C2)COC(=O)NC3=CC=C(C=C3)C(=O)NO
InChI
InChI=1S/C24H27N3O4/c1-3-27(4-2)15-17-5-7-21-14-18(6-8-20(21)13-17)16-31-24(29)25-22-11-9-19(10-12-22)23(28)26-30/h5-14,30H,3-4,15-16H2,1-2H3,(H,25,29)(H,26,28)
InChIKey
YALNUENQHAQXEA-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
9804992
ChEBI ID
CHEBI:94187
CAS Number
497833-27-9
DrugBank ID
DB12645
TTD ID
D0GH3Q

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Histone deacetylase (HDAC) TTBH0VX NOUNIPROTAC Inhibitor [1]
Histone deacetylase 1 (HDAC1) TT6R7JZ HDAC1_HUMAN Inhibitor [3], [4]
Janus kinase 2 (JAK-2) TTRMX3V JAK2_HUMAN Inhibitor [3], [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Duchenne dystrophy
ICD Disease Classification 8C70
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Histone deacetylase 1 (HDAC1) DTT HDAC1 5.21E-01 0.1 0.23
Molecular Expression Atlas (MEA) 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 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: 7490).
3 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.
4 Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
5 Selective JAK inhibitors in development for rheumatoid arthritis. Expert Opin Investig Drugs. 2014 Aug;23(8):1067-77.
6 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
8 Genetic determinants of response and survival in momelotinib-treated patients with myelofibrosis.Leukemia.2015 Mar;29(3):741-4.
9 National Cancer Institute Drug Dictionary (drug id 609888).
10 Company report (Portola Pharmaceuticals)
11 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
12 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. (Target id: 2048).
13 Clinical pipeline report, company report or official report of Concert Pharmaceuticals.
14 Transcription-independent heritability of induced histone modifications in the mouse preimplantation embryo. PLoS One. 2009 Jun 30;4(6):e6086.
15 Histone Deacetylase inhibitors: new promise in the treatment of immune and inflammatory diseases. Curr Drug Targets. 2010 Nov;11(11):1430-8.
16 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
17 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).
18 US patent application no. 2012,0302,505, Cyclodextrin-based polymers for therapeutic delivery.
19 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.
20 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
21 Protein methyltransferases as a target class for drug discovery. Nat Rev Drug Discov. 2009 Sep;8(9):724-32.
22 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
23 NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma. Blood. 2003 Oct 1;102(7):2615-22.
24 Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.
25 2011 Pipeline of 4SC AG.
26 Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov. 2006 Sep;5(9):769-84.