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
SMILES
NC1=CC=CC=C1NC(=O)C2=CC=C(CNC3=NC(=CC=N3)C4=CC=CN=C4)C=C2
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)
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 |
DescriptionCurator'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
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 | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL325 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18413790 |
0.15 µM [IC50] | ||
Target ID: CHEMBL1937 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18413790 |
0.29 µM [IC50] | ||
Target ID: CHEMBL1829 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18413790 |
1.66 µM [IC50] | ||
Target ID: CHEMBL3310 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18413790 |
0.59 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
161 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18495956 |
60 mg/m² single, oral dose: 60 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
MOCETINOSTAT plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1000 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18495956 |
60 mg/m² single, oral dose: 60 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
MOCETINOSTAT plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
10.9 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18495956 |
60 mg/m² single, oral dose: 60 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
MOCETINOSTAT plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Disc. AE: Neutropenic infection... AEs leading to discontinuation/dose reduction: Neutropenic infection (grade 5, 4.3%) Sources: |
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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
DLT: Nausea, Vomiting... Dose limiting toxicities: Nausea (grade 3, 25%) Sources: Vomiting (grade 3, 25%) Abdominal pain (grade 3, 25%) Diarrhea (grade 3, 25%) Fatigue (grade 3, 25%) Fatigue (grade 4, 25%) Deep vein thrombosis (grade 3, 25%) Mental status changes (grade 3, 25%) |
90 mg 3 times / day multiple, oral MTD Dose: 90 mg, 3 times / day Route: oral Route: multiple Dose: 90 mg, 3 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
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 Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
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 Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
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 Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
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 Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
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 Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
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 Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
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 Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
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 Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
Evaluation of the pharmacodynamic effects of MGCD0103 from preclinical models to human using a novel HDAC enzyme assay. | 2008 Jun 1 |
|
Histone deacetylase inhibitors in lymphoma and solid malignancies. | 2008 Mar |
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New clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer. | 2009 Jun 1 |
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Chemical phylogenetics of histone deacetylases. | 2010 Mar |
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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 |
|
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 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19747365
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18413790
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
Edited
Wed Apr 02 09:19:36 GMT 2025
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on
Wed Apr 02 09:19:36 GMT 2025
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Record UNII |
A6GWB8T96J
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Record Status |
Validated (UNII)
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Record Version |
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EU-Orphan Drug |
EU/3/07/526
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FDA ORPHAN DRUG |
435414
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FDA ORPHAN DRUG |
441514
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NCI_THESAURUS |
C1946
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UU-107
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MOCETINOSTAT
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Related Record | Type | Details | ||
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TARGET->NON-INHIBITOR |
Mocetinostat (MGCD0103) is a potent HDAC inhibitor but with no activity to HDAC8. Phase 2.
INHIBITOR
NOT CLINICALLY SIGNIFICANT
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TARGET -> INHIBITOR |
Potent HDAC inhibitor with most potency for HDAC1 in a cell-free assay.
INHIBITOR
IC50
|
||
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TARGET->NON-INHIBITOR |
Mocetinostat (MGCD0103) is a potent HDAC inhibitor but had no activity to HDAC5. Phase 2.
INHIBITOR
NOT CLINICALLY SIGNIFICANT
|
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TARGET -> INHIBITOR |
Mocetinostat (MGCD0103) is a potent HDAC inhibitor with a 2- to 10- fold selectivity against HDAC11. Phase 2.
INHIBITOR
|
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SALT/SOLVATE -> PARENT | |||
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TARGET->NON-INHIBITOR |
Mocetinostat (MGCD0103) is a potent HDAC inhibitor but with no activity to HDAC7. Phase 2.
INHIBITOR
NOT CLINICALLY SIGNIFICANT
|
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TARGET->NON-INHIBITOR |
Mocetinostat (MGCD0103) is a potent HDAC inhibitor but had no activity to HDAC4. Phase 2.
INHIBITOR
NOT CLINICALLY SIGNIFICANT
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TARGET -> INHIBITOR |
Mocetinostat (MGCD0103) is a potent HDAC inhibitor with a
2- to 10- fold selectivity against HDAC3. Phase 2.
INHIBITOR
|
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TARGET -> INHIBITOR |
Mocetinostat (MGCD0103) is a potent HDAC inhibitor with a 2- to 10- fold selectivity against HDAC2. Phase 2.
INHIBITOR
|
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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 | ||
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ACTIVE MOIETY |