MOCETINOSTAT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H20N6O
Molecular Weight	396.4445
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=C(NC(=O)C2=CC=C(CNC3=NC=CC(=N3)C4=CN=CC=C4)C=C2)C=CC=C1

InChI

InChIKey=HRNLUBSXIHFDHP-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C23H20N6O
Molecular Weight	396.4445
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=486941
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800020983 | http://mirati.com/programs/mocetinostat/ | http://meetinglibrary.asco.org/content/117882-132

Mocetinostat is an rationally designed, orally available, Class 1-selective, small molecule, 2-aminobenzamide HDAC inhibitor with potential antineoplastic activity. Mocetinostat binds to and inhibits Class 1 isoforms of HDAC, specifically HDAC 1, 2 and 3, which may result in epigenetic changes in tumor cells and so tumor cell death; although the exact mechanism has yet to be defined, tumor cell death may occur through the induction of apoptosis, differentiation, cell cycle arrest, inhibition of DNA repair, upregulation of tumor suppressors, down regulation of growth factors, oxidative stress, and autophagy, among others. It is undergoing clinical trials for treatment of various cancers including bladder cancer, diffuse large B cell lymphoma, follicular lymphoma, myelodysplastic syndromes, non-small cell lung cancer. Fatigue, weight loss or anorexia were most common treatment-related adverse events.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Histone deacetylase 1 51 Target ID: CHEMBL325 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18413790	Inhibitor 8297	0.15 µM [IC50]
Histone deacetylase 2 37 Target ID: CHEMBL1937 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18413790	Inhibitor 8297	0.29 µM [IC50]
Histone deacetylase 3 35 Target ID: CHEMBL1829 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18413790	Inhibitor 8297	1.66 µM [IC50]
Histone deacetylase 11 8 Target ID: CHEMBL3310 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18413790	Inhibitor 8297	0.59 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Chronic lymphocytic leukemia 59 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19747365	Primary	Phase II 1132	Unknown Approved Use Unknown
Myelodysplastic syndromes 58 Sources: http://adisinsight.springer.com/drugs/800020983 https://clinicaltrials.gov/ct2/show/NCT02018926	Primary	Phase II 1132	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: http://mirati.com/programs/mocetinostat/ http://adisinsight.springer.com/drugs/800020983	Primary	Phase II 1132	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
110 mg 3 times / week multiple, oral Highest studied dose Dose: 110 mg, 3 times / week Route: oral Route: multiple Dose: 110 mg, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/22033282 Page: p.6	unhealthy, ADULT n = 23 Health Status: unhealthy Condition: Hodgkin's lymphoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 23 Sources: https://pubmed.ncbi.nlm.nih.gov/22033282 Page: p.6	Disc. AE: Neutropenic infection... AEs leading to discontinuation/dose reduction: Neutropenic infection (grade 5, 4.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/22033282 Page: p.6
110 mg 3 times / week multiple, oral Highest studied dose Dose: 110 mg, 3 times / week Route: oral Route: multiple Dose: 110 mg, 3 times / week Co-administed with:: gemcitabine(1000 mg/m2, day 1 of three consecutive weeks, 4-week cycles) Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5	DLT: Nausea, Deep vein thrombosis... Dose limiting toxicities: Nausea (grade 3, 25%) Deep vein thrombosis (grade 3, 25%) Vomiting (grade 3, 25%) Abdominal pain (grade 3, 25%) Mental status changes (grade 3, 25%) Diarrhea (grade 3, 25%) Fatigue (grade 3, 25%) Fatigue (grade 4, 25%) Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5
90 mg 3 times / day multiple, oral MTD Dose: 90 mg, 3 times / day Route: oral Route: multiple Dose: 90 mg, 3 times / day Co-administed with:: gemcitabine(1000 mg/m2, day 1 of three consecutive weeks, 4-week cycles) Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5	Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5

AEs

AE	Significance	Dose	Population
Neutropenic infection	grade 5, 4.3% Disc. AE	110 mg 3 times / week multiple, oral Highest studied dose Dose: 110 mg, 3 times / week Route: oral Route: multiple Dose: 110 mg, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/22033282 Page: p.6	unhealthy, ADULT n = 23 Health Status: unhealthy Condition: Hodgkin's lymphoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 23 Sources: https://pubmed.ncbi.nlm.nih.gov/22033282 Page: p.6
Abdominal pain	grade 3, 25% DLT	110 mg 3 times / week multiple, oral Highest studied dose Dose: 110 mg, 3 times / week Route: oral Route: multiple Dose: 110 mg, 3 times / week Co-administed with:: gemcitabine(1000 mg/m2, day 1 of three consecutive weeks, 4-week cycles) Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5
Deep vein thrombosis	grade 3, 25% DLT	110 mg 3 times / week multiple, oral Highest studied dose Dose: 110 mg, 3 times / week Route: oral Route: multiple Dose: 110 mg, 3 times / week Co-administed with:: gemcitabine(1000 mg/m2, day 1 of three consecutive weeks, 4-week cycles) Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5
Diarrhea	grade 3, 25% DLT	110 mg 3 times / week multiple, oral Highest studied dose Dose: 110 mg, 3 times / week Route: oral Route: multiple Dose: 110 mg, 3 times / week Co-administed with:: gemcitabine(1000 mg/m2, day 1 of three consecutive weeks, 4-week cycles) Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5
Fatigue	grade 3, 25% DLT	110 mg 3 times / week multiple, oral Highest studied dose Dose: 110 mg, 3 times / week Route: oral Route: multiple Dose: 110 mg, 3 times / week Co-administed with:: gemcitabine(1000 mg/m2, day 1 of three consecutive weeks, 4-week cycles) Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5
Mental status changes	grade 3, 25% DLT	110 mg 3 times / week multiple, oral Highest studied dose Dose: 110 mg, 3 times / week Route: oral Route: multiple Dose: 110 mg, 3 times / week Co-administed with:: gemcitabine(1000 mg/m2, day 1 of three consecutive weeks, 4-week cycles) Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5
Nausea	grade 3, 25% DLT	110 mg 3 times / week multiple, oral Highest studied dose Dose: 110 mg, 3 times / week Route: oral Route: multiple Dose: 110 mg, 3 times / week Co-administed with:: gemcitabine(1000 mg/m2, day 1 of three consecutive weeks, 4-week cycles) Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5
Vomiting	grade 3, 25% DLT	110 mg 3 times / week multiple, oral Highest studied dose Dose: 110 mg, 3 times / week Route: oral Route: multiple Dose: 110 mg, 3 times / week Co-administed with:: gemcitabine(1000 mg/m2, day 1 of three consecutive weeks, 4-week cycles) Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5
Fatigue	grade 4, 25% DLT	110 mg 3 times / week multiple, oral Highest studied dose Dose: 110 mg, 3 times / week Route: oral Route: multiple Dose: 110 mg, 3 times / week Co-administed with:: gemcitabine(1000 mg/m2, day 1 of three consecutive weeks, 4-week cycles) Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/29238851 Page: p.5

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY116244	https://www.001chemical.com/chem/search?q=DY116244
1PlusChem LLC	1P0039R9	https://www.1pchem.com/search?query=1P0039R9
A2B Chem	AB51813	http://a2bchem.com/prod/AB51813
AK Scientific	X7532	https://aksci.com/item_detail.php?cat=X7532
AOBIOUS INC	AOB87751	http://aobious.com/aobious/search?search_query=AOB87751
Ambeed	A102453	http://www.ambeed.com/search/Search.html?keyword=A102453
Angene	AGN-PC-0MUSW4	http://www.angenechemical.com/productshow/AGN-PC-0MUSW4.html
ApexBio Technology	A4089	https://www.apexbt.com/catalogsearch/result/?q=A4089
AstaTech	40645	http://astatechinc.com/CPSResult.php?CRNO=40645
Axon MedChem	2505	https://www.axonmedchem.com/product/2505
BLD Pharm	BD305950	http://www.bldpharm.com/search/Search.html?keyword=BD305950
BOC Sciences	726169-73-9	http://www.bocsci.com/description.asp?cas=726169-73-9
Capot Chemical	24623	https://www.capotchem.com/search.do?q=24623
Cayman Chemical	18287	http://www.caymanchem.com/app/template/Product.vm/catalog/18287
Chem Scene	CS-0502	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0502
ChemShuttle	101210	https://www.chemshuttle.com/catalogsearch/result/?q=101210
Excenen	EX-A049	http://www.excenen.com/searchresultlist.php?id=EX-A049
Exclusive Chemistry	2284	http://www.exchemistry.com/chem-catalog/product-2284.html
KeyOrganics	BD-0114	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=BD-0114
Lab Network	LN01306423	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01306423
Lab Seeker	SC-85911	http://www.labseeker.com/search.php?keywords=SC-85911&category=0
LabSeeker	SC-85911	http://www.labseeker.com/search.php?keywords=SC-85911&category=0
Matrix Scientific	143829	http://www.matrixscientific.com/143829.html
MedChem Express	HY-12164	https://www.medchemexpress.com/search.html?q=HY-12164&ft=&fa=&fp=
MolPort	MolPort-009-679-400	https://www.molport.com/shop/molecule-link/MolPort-009-679-400
Molcore	MC116244	http://www.molcore.com/CatMC116244.html
Molnova	M15781	https://www.molnova.com/en/serch-list.html?keywords=M15781
MuseChem	I004705	https://www.musechem.com/product/I004705.html
Ryan Scientific	Macitentan	https://ryansci.com/products?q=Macitentan&list_q=&search_type=exact
ShangHai Biochempartner	BCP000119	http://www.biochempartner.com/search_BCP000119
ShangHai Biochempartner	BCP01814	http://www.biochempartner.com/search_BCP01814
TargetMol	T2512	https://www.targetmol.com/search?keyword=T2512
Toronto Research Chemicals	D435235	https://www.trc-canada.com/product-detail/?CatNum=D435235
Toronto Research Chemicals	M481090	https://www.trc-canada.com/product-detail/?CatNum=M481090
eMolecules	32176474	https://orderbb.emolecules.com/search/#?query=32176474
eMolecules	85163381	https://orderbb.emolecules.com/search/#?query=85163381
eNovation Chemicals	D619806	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D619806&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-2367278974	https://mcule.com/MCULE-2367278974/
mcule	MCULE-4492645927	https://mcule.com/MCULE-4492645927/

PubMed

Title	Date	PubMed
Drug evaluation: MGCD-0103, a histone deacetylase inhibitor for the treatment of cancer.	2007 Jun	17621879
MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo.	2008 Apr	18413790
Phase I study of MGCD0103 given as a three-times-per-week oral dose in patients with advanced solid tumors.	2008 Apr 20	18421048
Promising antitumor activity with MGCD0103, a novel isotype-selective histone deacetylase inhibitor.	2008 Aug	18616420
Phase 1 study of the oral isotype specific histone deacetylase inhibitor MGCD0103 in leukemia.	2008 Aug 15	18495956
Effects of a selection of histone deacetylase inhibitors on mast cell activation and airway and colonic smooth muscle contraction.	2008 Dec 20	18805511
Design and synthesis of 4-[(s-triazin-2-ylamino)methyl]-N-(2-aminophenyl)-benzamides and their analogues as a novel class of histone deacetylase inhibitors.	2008 Feb 1	18160287
Discovery of N-(2-aminophenyl)-4-[(4-pyridin-3-ylpyrimidin-2-ylamino)methyl]benzamide (MGCD0103), an orally active histone deacetylase inhibitor.	2008 Jul 24	18570366
Evaluation of the pharmacodynamic effects of MGCD0103 from preclinical models to human using a novel HDAC enzyme assay.	2008 Jun 1	18519775
Histone deacetylase inhibitors in lymphoma and solid malignancies.	2008 Mar	18366289
Probing the elusive catalytic activity of vertebrate class IIa histone deacetylases.	2008 Mar 15	18308563
SAR and biological evaluation of analogues of a small molecule histone deacetylase inhibitor N-(2-aminophenyl)-4-((4-(pyridin-3-yl)pyrimidin-2-ylamino)methyl)benzamide (MGCD0103).	2009 Feb 1	19114304
Acquired vorinostat resistance shows partial cross-resistance to 'second-generation' HDAC inhibitors and correlates with loss of histone acetylation and apoptosis but not with altered HDAC and HAT activities.	2009 Jun	19322073
New clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer.	2009 Jun 1	19486511
Clinical studies of histone deacetylase inhibitors.	2009 Jun 15	19509172
A systematic assessment of radiation dose enhancement by 5-Aza-2'-deoxycytidine and histone deacetylase inhibitors in head-and-neck squamous cell carcinoma.	2009 Mar 1	19215824
Phase II study of the histone deacetylase inhibitor MGCD0103 in patients with previously treated chronic lymphocytic leukaemia.	2009 Nov	19747365
The combination of a histone deacetylase inhibitor with the Bcl-2 homology domain-3 mimetic GX15-070 has synergistic antileukemia activity by activating both apoptosis and autophagy.	2010 Aug 1	20538760
Histone deacetylase inhibitors: potential targets responsible for their anti-cancer effect.	2010 Dec	21161327
Histone deacetylase inhibitors in Hodgkin lymphoma.	2010 Dec	21127943
Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents.	2010 Feb 4	20132536
Chemical phylogenetics of histone deacetylases.	2010 Mar	20139990
Effect of endogenous and synthetic antioxidants on hydrogen peroxide-induced guinea-pig colon contraction.	2010 Mar	20033256
Effect of antioxidants on airway smooth muscle contraction: action of lipoic acid and some of its novel derivatives on guinea pig tracheal smooth muscle.	2010 Mar	20013027
[New approach to determine the pharmacodynamic effects of histone deacetylases inhibitors].	2010 May	20425766
The histone deacetylase inhibitor MGCD0103 induces apoptosis in B-cell chronic lymphocytic leukemia cells through a mitochondria-mediated caspase activation cascade.	2010 May	20406947
The class I HDAC inhibitor MGCD0103 induces cell cycle arrest and apoptosis in colon cancer initiating cells by upregulating Dickkopf-1 and non-canonical Wnt signaling.	2010 Nov	21317455
Histone deacetylase inhibitors in the treatment of lymphoma.	2010 Nov	21122478
The class-I HDAC inhibitor MGCD0103 induces apoptosis in Hodgkin lymphoma cell lines and synergizes with proteasome inhibitors by an HDAC6-independent mechanism.	2010 Nov	20880107
The combination of a histone deacetylase inhibitor with the BH3-mimetic GX15-070 has synergistic antileukemia activity by activating both apoptosis and autophagy.	2010 Oct	20729640
The histone deacetylase inhibitor MGCD0103 has both deacetylase and microtubule inhibitory activity.	2010 Sep	20538840
Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors.	2011 Jul 14	21650221
Epigenetic modulation of MAGE-A3 antigen expression in multiple myeloma following treatment with the demethylation agent 5-azacitidine and the histone deacetlyase inhibitor MGCD0103.	2011 May	21171821
Natural indoles, indole-3-carbinol and 3,3'-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression.	2014 Jan 1	24200994
Induction of USP17 by combining BET and HDAC inhibitors in breast cancer cells.	2015 Oct 20	26378038

Patents

Sample Use Guides

In Vivo Use Guide

Starting dose of 85 mg three times per week for four weeks. Dose escalation to 110 mg three times per week was permitted beginning with cycle 2 in patients who failed to achieve a complete response.

Route of Administration: Oral

In Vitro Use Guide

The inhibitory activity of MGCD0103 reaches the maximum plateau at 6 μM, and the maximal inhibitable enzyme pool affected by MGCD0103 is 75% of the total enzyme activity in HCT116 cells.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:34:19 UTC 2023` Edited by `admin` on `Sat Dec 16 17:34:19 UTC 2023`
Record UNII	A6GWB8T96J
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MOCETINOSTAT

Official Name

English

MGCD-0103

Code

English

BENZAMIDE, N-(2-AMINOPHENYL)-4-(((4-(3-PYRIDINYL)-2-PYRIMIDINYL)AMINO)METHYL)-

Systematic Name

English

Mocetinostat [WHO-DD]

Common Name

English

mocetinostat [INN]

Common Name

English

N-(2-Aminophenyl)-4-({[4-(pyridin-3-yl)pyrimidin-2-yl]amino}methyl)benzamide

Systematic Name

English

MOCETINOSTAT [USAN]

Common Name

English

MGCD0103

Code

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/07/526