U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of MOCETINOSTAT

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
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.15 µM [IC50]
0.29 µM [IC50]
1.66 µM [IC50]
0.59 µM [IC50]
Conditions
Doses

Doses

DosePopulationAdverse 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: 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: Page: p.6
Disc. AE: Neutropenic infection...
AEs leading to
discontinuation/dose reduction:
Neutropenic infection (grade 5, 4.3%)
Sources: 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: 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: 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: 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: 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: Page: p.5
AEs

AEs

AESignificanceDosePopulation
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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: Page: p.5
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Promising antitumor activity with MGCD0103, a novel isotype-selective histone deacetylase inhibitor.
2008 Aug
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
New clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer.
2009 Jun 1
Clinical studies of histone deacetylase inhibitors.
2009 Jun 15
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
Histone deacetylase inhibitors: potential targets responsible for their anti-cancer effect.
2010 Dec
Chemical phylogenetics of histone deacetylases.
2010 Mar
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
Histone deacetylase inhibitors in the treatment of lymphoma.
2010 Nov
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
Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors.
2011 Jul 14
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
Patents

Sample Use Guides

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
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 GMT 2023
Edited
by admin
on Sat Dec 16 17:34:19 GMT 2023
Record UNII
A6GWB8T96J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MOCETINOSTAT
INN   USAN   WHO-DD  
INN   USAN  
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
Created by admin on Sat Dec 16 17:34:19 GMT 2023 , Edited by admin on Sat Dec 16 17:34:19 GMT 2023
FDA ORPHAN DRUG 435414
Created by admin on Sat Dec 16 17:34:19 GMT 2023 , Edited by admin on Sat Dec 16 17:34:19 GMT 2023
FDA ORPHAN DRUG 441514
Created by admin on Sat Dec 16 17:34:19 GMT 2023 , Edited by admin on Sat Dec 16 17:34:19 GMT 2023
NCI_THESAURUS C1946
Created by admin on Sat Dec 16 17:34:19 GMT 2023 , Edited by admin on Sat Dec 16 17:34:19 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID80222945
Created by admin on Sat Dec 16 17:34:19 GMT 2023 , Edited by admin on Sat Dec 16 17:34:19 GMT 2023
PRIMARY
USAN
UU-107
Created by admin on Sat Dec 16 17:34:19 GMT 2023 , Edited by admin on Sat Dec 16 17:34:19 GMT 2023
PRIMARY
ChEMBL
CHEMBL272980
Created by admin on Sat Dec 16 17:34:19 GMT 2023 , Edited by admin on Sat Dec 16 17:34:19 GMT 2023
PRIMARY
SMS_ID
100000141555
Created by admin on Sat Dec 16 17:34:19 GMT 2023 , Edited by admin on Sat Dec 16 17:34:19 GMT 2023
PRIMARY
PUBCHEM
9865515
Created by admin on Sat Dec 16 17:34:19 GMT 2023 , Edited by admin on Sat Dec 16 17:34:19 GMT 2023
PRIMARY
EVMPD
SUB93367
Created by admin on Sat Dec 16 17:34:19 GMT 2023 , Edited by admin on Sat Dec 16 17:34:19 GMT 2023
PRIMARY
NCI_THESAURUS
C62521
Created by admin on Sat Dec 16 17:34:19 GMT 2023 , Edited by admin on Sat Dec 16 17:34:19 GMT 2023
PRIMARY
WIKIPEDIA
MOCETINOSTAT
Created by admin on Sat Dec 16 17:34:19 GMT 2023 , Edited by admin on Sat Dec 16 17:34:19 GMT 2023
PRIMARY
FDA UNII
A6GWB8T96J
Created by admin on Sat Dec 16 17:34:19 GMT 2023 , Edited by admin on Sat Dec 16 17:34:19 GMT 2023
PRIMARY
INN
9086
Created by admin on Sat Dec 16 17:34:19 GMT 2023 , Edited by admin on Sat Dec 16 17:34:19 GMT 2023
PRIMARY
DRUG BANK
DB11830
Created by admin on Sat Dec 16 17:34:19 GMT 2023 , Edited by admin on Sat Dec 16 17:34:19 GMT 2023
PRIMARY
CAS
726169-73-9
Created by admin on Sat Dec 16 17:34:19 GMT 2023 , Edited by admin on Sat Dec 16 17:34:19 GMT 2023
PRIMARY
Related Record Type Details
TARGET->NON-INHIBITOR
Mocetinostat (MGCD0103) is a potent HDAC inhibitor but with no activity to HDAC8. Phase 2.
INHIBITOR
NOT CLINICALLY SIGNIFICANT
TARGET -> INHIBITOR
Potent HDAC inhibitor with most potency for HDAC1 in a cell-free assay.
INHIBITOR
IC50
TARGET->NON-INHIBITOR
Mocetinostat (MGCD0103) is a potent HDAC inhibitor but had no activity to HDAC5. Phase 2.
INHIBITOR
NOT CLINICALLY SIGNIFICANT
TARGET -> INHIBITOR
Mocetinostat (MGCD0103) is a potent HDAC inhibitor with a 2- to 10- fold selectivity against HDAC11. Phase 2.
INHIBITOR
SALT/SOLVATE -> PARENT
TARGET->NON-INHIBITOR
Mocetinostat (MGCD0103) is a potent HDAC inhibitor but with no activity to HDAC7. Phase 2.
INHIBITOR
NOT CLINICALLY SIGNIFICANT
TARGET->NON-INHIBITOR
Mocetinostat (MGCD0103) is a potent HDAC inhibitor but had no activity to HDAC4. Phase 2.
INHIBITOR
NOT CLINICALLY SIGNIFICANT
TARGET -> INHIBITOR
Mocetinostat (MGCD0103) is a potent HDAC inhibitor with a 2- to 10- fold selectivity against HDAC3. Phase 2.
INHIBITOR
TARGET -> INHIBITOR
Mocetinostat (MGCD0103) is a potent HDAC inhibitor with a 2- to 10- fold selectivity against HDAC2. Phase 2.
INHIBITOR
TARGET->NON-INHIBITOR
Mocetinostat (MGCD0103) is a potent HDAC inhibitor with no activity to HDAC6. Phase 2.
INHIBITOR
NOT CLINICALLY SIGNIFICANT
Related Record Type Details
ACTIVE MOIETY