MOCETINOSTAT

Investigational

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 8228	0.15 µM [IC50]
Histone deacetylase 2 37 Target ID: CHEMBL1937 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18413790	Inhibitor 8228	0.29 µM [IC50]
Histone deacetylase 3 35 Target ID: CHEMBL1829 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18413790	Inhibitor 8228	1.66 µM [IC50]
Histone deacetylase 11 8 Target ID: CHEMBL3310 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18413790	Inhibitor 8228	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 1144	Unknown Approved Use Unknown
Myelodysplastic syndromes 57 Sources: http://adisinsight.springer.com/drugs/800020983 https://clinicaltrials.gov/ct2/show/NCT02018926	Primary	Phase II 1144	Unknown Approved Use Unknown
Non-small cell lung cancer 201 Sources: http://mirati.com/programs/mocetinostat/ http://adisinsight.springer.com/drugs/800020983	Primary	Phase II 1144	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
Promising antitumor activity with MGCD0103, a novel isotype-selective histone deacetylase inhibitor.	2008 Aug	18616420
Effects of a selection of histone deacetylase inhibitors on mast cell activation and airway and colonic smooth muscle contraction.	2008 Dec 20	18805511
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
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 in Hodgkin lymphoma.	2010 Dec	21127943
Chemical phylogenetics of histone deacetylases.	2010 Mar	20139990
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
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
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

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 `Thu Jul 06 22:56:43 UTC 2023` Edited by `admin` on `Thu Jul 06 22:56:43 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