Pracinostat

Identification

Name
Pracinostat
Accession Number
DB05223
Type
Small Molecule
Groups
Investigational
Description

Pracinostat is a novel HDAC inhibitor with improved in vivo properties compared to other HDAC inhibitors currently in clinical trials, allowing oral dosing. Data demonstrate that Pracinostat is a potent and effective anti-tumor drug with potential as an oral therapy for a variety of human hematological and solid tumors.

Structure
Thumb
Synonyms
Not Available
External IDs
SB 939 / SB-939 / SB939
Categories
UNII
GPO2JN4UON
CAS number
Not Available
Weight
Average: 358.486
Monoisotopic: 358.236876222
Chemical Formula
C20H30N4O2
InChI Key
JHDKZFFAIZKUCU-ZRDIBKRKSA-N
InChI
InChI=1S/C20H30N4O2/c1-4-7-8-19-21-17-15-16(10-12-20(25)22-26)9-11-18(17)24(19)14-13-23(5-2)6-3/h9-12,15,26H,4-8,13-14H2,1-3H3,(H,22,25)/b12-10+
IUPAC Name
(2E)-3-{2-butyl-1-[2-(diethylamino)ethyl]-1H-1,3-benzodiazol-5-yl}-N-hydroxyprop-2-enamide
SMILES
CCCCC1=NC2=CC(\C=C\C(=O)NO)=CC=C2N1CCN(CC)CC

Pharmacology

Indication

For the treatment of various forms of cancer.

Structured Indications
Not Available
Pharmacodynamics

SB939 is a novel compound with superior pharmaceutical, metabolic and pharmacokinetic properties. SB939 has demonstrated excellent in vivo anti-tumour activity in various animal models with dose proportional pharmacodynamic effects. The pharmacokinetics and pharmacodynamic attributes of SB939 explain and differentiate it as the best in class HDAC inhibitor.

Mechanism of action

Inhibition of HDAC activity allows for the accumulation of acetyl groups on the histone lysine residues resulting in an open chromatin structure and transcriptional activation. In vitro, SB939 causes the accumulation of acetylated histones and induces cell cycle arrest and/or apoptosis of some transformed cells. The mechanism of the antineoplastic effect of SB939 has not been fully characterized.

TargetActionsOrganism
UHistone deacetylase 1Not AvailableHuman
UHistone deacetylase 2Not AvailableHuman
UHistone deacetylase 3Not AvailableHuman
UHistone deacetylase 6Not AvailableHuman
Absorption

Oral bioavailability in mice is 34%.

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
  • Humans and other mammals
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 Pracinostat.Approved
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
49855250
PubChem Substance
347827719
ChemSpider
25027185
BindingDB
50353227
ChEMBL
CHEMBL1851943

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedOtherHealthy Volunteers / Moderate to Heavy Smokers / Non-Smokers1
1CompletedOtherHealthy Volunteers / Non-Smokers1
1CompletedTreatmentLeukemias / Tumors, Solid1
1CompletedTreatmentMalignancies, Hematologic / Myelodysplastic Syndrome / Tumors, Solid1
2Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2Active Not RecruitingTreatmentMyelodysplastic Syndrome1
2Active Not RecruitingTreatmentMyeloproliferative Disorders1
2CompletedTreatmentMetastatic Sarcoma1
2CompletedTreatmentMyelodysplastic Syndrome / Smith-Magenis Syndrome1
2CompletedTreatmentMyeloproliferative Disorders1
2CompletedTreatmentProstate Cancer1
2RecruitingTreatmentMyelodysplastic Syndromes1
3RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0306 mg/mLALOGPS
logP3.98ALOGPS
logP2.57ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)9.3ChemAxon
pKa (Strongest Basic)9.9ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area70.39 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity106.24 m3·mol-1ChemAxon
Polarizability42.85 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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 cinnamic acids and derivatives. These are organic aromatic compounds containing a benzene and a carboxylic acid group (or a derivative thereof) forming 3-phenylprop-2-enoic acid.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Cinnamic acids and derivatives
Sub Class
Not Available
Direct Parent
Cinnamic acids and derivatives
Alternative Parents
Benzimidazoles / Styrenes / N-substituted imidazoles / Heteroaromatic compounds / Trialkylamines / Hydroxamic acids / Amino acids and derivatives / Azacyclic compounds / Organic oxides / Hydrocarbon derivatives
show 1 more
Substituents
Cinnamic acid or derivatives / Benzimidazole / Styrene / Benzenoid / N-substituted imidazole / Azole / Heteroaromatic compound / Imidazole / Amino acid or derivatives / Hydroxamic acid
show 14 more
Molecular Framework
Aromatic heteropolycyclic 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
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
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion 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
HDAC6
Uniprot ID
Q9UBN7
Uniprot Name
Histone deacetylase 6
Molecular Weight
131418.19 Da

Drug created on October 21, 2007 16:24 / Updated on December 01, 2017 15:35