Mocetinostat

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Mocetinostat
Accession Number
DB11830  (DB05651)
Type
Small Molecule
Groups
Investigational
Description

Mocetinostat has been used in trials studying the treatment of Lymphoma, Urothelial Carcinoma, Relapsed and Refractory, Myelodysplastic Syndrome, and Metastatic Leiomyosarcoma, among others.

Structure
Thumb
Synonyms
Not Available
External IDs
MGCD-0103 / MGCD0103
Categories
UNII
A6GWB8T96J
CAS number
726169-73-9
Weight
Average: 396.454
Monoisotopic: 396.169859288
Chemical Formula
C23H20N6O
InChI Key
HRNLUBSXIHFDHP-UHFFFAOYSA-N
InChI
InChI=1S/C23H20N6O/c24-19-5-1-2-6-21(19)28-22(30)17-9-7-16(8-10-17)14-27-23-26-13-11-20(29-23)18-4-3-12-25-15-18/h1-13,15H,14,24H2,(H,28,30)(H,26,27,29)
IUPAC Name
N-(2-aminophenyl)-4-({[4-(pyridin-3-yl)pyrimidin-2-yl]amino}methyl)benzamide
SMILES
NC1=CC=CC=C1NC(=O)C1=CC=C(CNC2=NC=CC(=N2)C2=CC=CN=C2)C=C1

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics

All HDAC inhibitors induce histone H3 hyperacetylation, correlating with inhibition of proliferation, induction of cell differentiation and apoptosis.

Mechanism of action

Mocetinostat is a novel isotypic-selective inhibitor of the enzyme histone deacetylase (HDAC). HDAC inhibitors act by turning on tumour suppressor genes that have been inappropriately turned off. Tumour suppressor genes are a natural defense against cancer. It is therefore hypothesized that specifically inhibiting those HDACs involved in cancer with Mocetinostat may restore normal cell function and reduce or inhibit tumour growth.

TargetActionsOrganism
UHistone deacetylase 1Not AvailableHuman
UHistone deacetylase 3Not AvailableHuman
UHistone deacetylase 2Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Mocetinostat.Approved
Food Interactions
Not Available

References

General References
  1. Kell J: Drug evaluation: MGCD-0103, a histone deacetylase inhibitor for the treatment of cancer. Curr Opin Investig Drugs. 2007 Jun;8(6):485-92. [PubMed:17621879]
  2. Beckers T, Burkhardt C, Wieland H, Gimmnich P, Ciossek T, Maier T, Sanders K: Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group. Int J Cancer. 2007 Sep 1;121(5):1138-48. [PubMed:17455259]
  3. Khan N, Jeffers M, Kumar S, Hackett C, Boldog F, Khramtsov N, Qian X, Mills E, Berghs SC, Carey N, Finn PW, Collins LS, Tumber A, Ritchie JW, Jensen PB, Lichenstein HS, Sehested M: Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. Biochem J. 2008 Jan 15;409(2):581-9. [PubMed:17868033]
External Links
PubChem Compound
9865515
PubChem Substance
347828176
ChemSpider
8041206
BindingDB
24624
ChEBI
94525
ChEMBL
CHEMBL272980

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentLeukemias / Myelodysplastic Syndromes2
1CompletedTreatmentNon Hodgkin Lymphoma (NHL) / Tumors1
1Not Yet RecruitingTreatmentResectable Squamous Cell Carcinoma of Oral Cavity / Squamous Cell Carcinoma Mouth / Squamous Cell Carcinoma, Head And Neck1
1RecruitingTreatmentLung Cancers1
1, 2Active Not RecruitingTreatmentDiffuse Large B-Cell Lymphoma and Follicular Lymphoma / Malignant Lymphomas / Relapsed and Refractory1
1, 2Active Not RecruitingTreatmentLymphoma, Hodgkins1
1, 2CompletedTreatmentAcute Myelogenous Leukaemia (AML) / Myelodysplastic Syndrome1
1, 2CompletedTreatmentMyelodysplastic Syndrome1
1, 2CompletedTreatmentTumors1
1, 2RecruitingTreatmentCancer, Advanced1
2CompletedTreatmentLymphocytic Leukemia, Chronic1
2CompletedTreatmentMalignant Lymphomas1
2CompletedTreatmentMetastatic Leiomyosarcoma1
2CompletedTreatmentTransitional Cell Carcinoma1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2TerminatedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes (MDS)1
2TerminatedTreatmentLymphoma, Hodgkins1
2TerminatedTreatmentLymphoma, Hodgkins / Non-Hodgkin Lymphoma (Follicular or Large Diffuse B-cell Lymphoma or Mantle Cell Lymphoma)1
2TerminatedTreatmentMyelodysplastic Syndromes / Myelogenous Leukemia, Acute1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00854 mg/mLALOGPS
logP3.01ALOGPS
logP3ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)13.98ChemAxon
pKa (Strongest Basic)4.37ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area105.82 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity120.32 m3·mol-1ChemAxon
Polarizability42.56 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzanilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with a benzene ring. They have the general structure RNC(=O)R', where R,R'= benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Benzanilides
Alternative Parents
Pyridinylpyrimidines / Benzamides / Aniline and substituted anilines / Benzylamines / Benzoyl derivatives / Secondary alkylarylamines / Aminopyrimidines and derivatives / Pyridines and derivatives / Heteroaromatic compounds / Secondary carboxylic acid amides
show 7 more
Substituents
Benzanilide / Pyridinylpyrimidine / Benzamide / Benzoic acid or derivatives / Benzoyl / Benzylamine / Aniline or substituted anilines / Aminopyrimidine / Secondary aliphatic/aromatic amine / Pyridine
show 19 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transcription regulatory region sequence-specific dna binding
Specific Function
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...
Gene Name
HDAC1
Uniprot ID
Q13547
Uniprot Name
Histone deacetylase 1
Molecular Weight
55102.615 Da
References
  1. Beckers T, Burkhardt C, Wieland H, Gimmnich P, Ciossek T, Maier T, Sanders K: Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group. Int J Cancer. 2007 Sep 1;121(5):1138-48. [PubMed:17455259]
  2. Khan N, Jeffers M, Kumar S, Hackett C, Boldog F, Khramtsov N, Qian X, Mills E, Berghs SC, Carey N, Finn PW, Collins LS, Tumber A, Ritchie JW, Jensen PB, Lichenstein HS, Sehested M: Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. Biochem J. 2008 Jan 15;409(2):581-9. [PubMed:17868033]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transcription factor binding
Specific Function
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. Histone deacetylation gives a tag for ...
Gene Name
HDAC3
Uniprot ID
O15379
Uniprot Name
Histone deacetylase 3
Molecular Weight
48847.385 Da
References
  1. Beckers T, Burkhardt C, Wieland H, Gimmnich P, Ciossek T, Maier T, Sanders K: Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group. Int J Cancer. 2007 Sep 1;121(5):1138-48. [PubMed:17455259]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transcription factor binding
Specific Function
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...
Gene Name
HDAC2
Uniprot ID
Q92769
Uniprot Name
Histone deacetylase 2
Molecular Weight
55363.855 Da
References
  1. Khan N, Jeffers M, Kumar S, Hackett C, Boldog F, Khramtsov N, Qian X, Mills E, Berghs SC, Carey N, Finn PW, Collins LS, Tumber A, Ritchie JW, Jensen PB, Lichenstein HS, Sehested M: Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. Biochem J. 2008 Jan 15;409(2):581-9. [PubMed:17868033]

Drug created on October 20, 2016 14:51 / Updated on December 01, 2017 16:24