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Details

Stereochemistry ACHIRAL
Molecular Formula C20H30N4O2
Molecular Weight 358.4786
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of PRACINOSTAT

SMILES

CCCCc1nc2cc(ccc2n1CCN(CC)CC)/C(/[H])=C(\[H])/C(=NO)O

InChI

InChIKey=JHDKZFFAIZKUCU-ZRDIBKRKSA-N
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+

HIDE SMILES / InChI

Molecular Formula C20H30N4O2
Molecular Weight 358.4786
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Pracinostat is a pan-histone deacetylase inhibitor being tested in phase II of clinical trials for the treatment of sarcoma, prostate cancer, acute myeloid leukemia, myelofibrosis, myelodysplastic syndrome. The drug was shown to be active in vitro on HCT116 and HL-60 cells.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
120 mg 3 times / week multiple, oral
MTD
Dose: 120 mg, 3 times / week
Route: oral
Route: multiple
Dose: 120 mg, 3 times / week
Sources: Page: p.5
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: Hematological tumors
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.5
DLT: febrile neutropeni...
Dose limiting toxicities:
febrile neutropeni (16.7%)
Sources: Page: p.5
80 mg 3 times / week multiple, oral
MTD
Dose: 80 mg, 3 times / week
Route: oral
Route: multiple
Dose: 80 mg, 3 times / week
Sources: Page: p.2518
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 6
Sources: Page: p.2518
DLT: Fatigue, Troponin T increased...
Dose limiting toxicities:
Fatigue (grade 3, 16.7%)
Troponin T increased (grade 3, 16.7%)
QTc interval prolongation (grade 3, 16.7%)
Sources: Page: p.2518
AEs

AEs

AESignificanceDosePopulation
febrile neutropeni 16.7%
DLT
120 mg 3 times / week multiple, oral
MTD
Dose: 120 mg, 3 times / week
Route: oral
Route: multiple
Dose: 120 mg, 3 times / week
Sources: Page: p.5
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: Hematological tumors
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.5
Fatigue grade 3, 16.7%
DLT
80 mg 3 times / week multiple, oral
MTD
Dose: 80 mg, 3 times / week
Route: oral
Route: multiple
Dose: 80 mg, 3 times / week
Sources: Page: p.2518
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 6
Sources: Page: p.2518
Troponin T increased grade 3, 16.7%
DLT
80 mg 3 times / week multiple, oral
MTD
Dose: 80 mg, 3 times / week
Route: oral
Route: multiple
Dose: 80 mg, 3 times / week
Sources: Page: p.2518
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 6
Sources: Page: p.2518
QTc interval prolongation grade 3, 16.7%
DLT, Disc. AE
80 mg 3 times / week multiple, oral
MTD
Dose: 80 mg, 3 times / week
Route: oral
Route: multiple
Dose: 80 mg, 3 times / week
Sources: Page: p.2518
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 6
Sources: Page: p.2518
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Deactylase inhibition in myeloproliferative neoplasms.
2010 Dec
A novel histone deacetylase inhibitor Chidamide induces apoptosis of human colon cancer cells.
2010 Feb 5
SB939, a novel potent and orally active histone deacetylase inhibitor with high tumor exposure and efficacy in mouse models of colorectal cancer.
2010 Mar
Vorinostat in acute myeloid leukemia and myelodysplastic syndromes.
2011 Feb
Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors.
2011 Jul 14
Discovery of (2E)-3-{2-butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl}-N-hydroxyacrylamide (SB939), an orally active histone deacetylase inhibitor with a superior preclinical profile.
2011 Jul 14
Antimalarial activity of the anticancer histone deacetylase inhibitor SB939.
2012 Jul
Synthesis, antimalarial properties, and SAR studies of alkoxyurea-based HDAC inhibitors.
2014 Mar
Patents

Patents

Sample Use Guides

The recommended dose is 60 mg given by mouth every other day, three times weekly for 3 weeks
Route of Administration: Oral
Three micrograms of protein lysate from either HCT116 or HL-60 cells were treated for 24 hours with 2 uM pracinostat to obtain a strong acetylation of K9 and K14 of histone H3. The lowest concentration of the drug leading to acH3 was 22 ng/mL (0.06 uM) for both HCT-116 and HL-60 cells treated for 24 hours with pracinostat. In HL-60 cells, maximal acH3 levels were reached at 1 uM not increasing further after treatment with 2 uM.
Substance Class Chemical
Created
by admin
on Sat Jun 26 10:27:41 UTC 2021
Edited
by admin
on Sat Jun 26 10:27:41 UTC 2021
Record UNII
GPO2JN4UON
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PRACINOSTAT
INN   WHO-DD  
INN  
Official Name English
SB-939
Code English
SB939
Common Name English
SB 939
Code English
KAEMPFEROL 3-O-.BETA.-D-(6-E-P-COUMAROYLGLUCOSIDE)
Common Name English
(2E)-3-(2-BUTYL-1-(2-(DIMETHYLAMINO)ETHYL)-1H-BENZIMIDAZOL-5-YL)-N-HYDROXYPROP-2-ENAMIDE
Systematic Name English
PRACINOSTAT [INN]
Common Name English
PRACINOSTAT [WHO-DD]
Common Name English
(E)-3-(2-BUTYL-1-(2-DIETHYLAMINOETHYL)-1H-BENZIMIDAZOL-5-YL)-N-HYDROXY-2-PROPENAMIDE
Systematic Name English
2-PROPENAMIDE, 3-(2-BUTYL-1-(2-(DIETHYLAMINO)ETHYL)-1H-BENZIMIDAZOL-5-YL)-N-HYDROXY-, (2E)-
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C1946
Created by admin on Sat Jun 26 10:27:41 UTC 2021 , Edited by admin on Sat Jun 26 10:27:41 UTC 2021
FDA ORPHAN DRUG 421313
Created by admin on Sat Jun 26 10:27:41 UTC 2021 , Edited by admin on Sat Jun 26 10:27:41 UTC 2021
EU-Orphan Drug EU/3/17/1927
Created by admin on Sat Jun 26 10:27:41 UTC 2021 , Edited by admin on Sat Jun 26 10:27:41 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C71708
Created by admin on Sat Jun 26 10:27:41 UTC 2021 , Edited by admin on Sat Jun 26 10:27:41 UTC 2021
PRIMARY
PUBCHEM
49855250
Created by admin on Sat Jun 26 10:27:41 UTC 2021 , Edited by admin on Sat Jun 26 10:27:41 UTC 2021
PRIMARY
CAS
929016-96-6
Created by admin on Sat Jun 26 10:27:41 UTC 2021 , Edited by admin on Sat Jun 26 10:27:41 UTC 2021
PRIMARY
FDA UNII
GPO2JN4UON
Created by admin on Sat Jun 26 10:27:41 UTC 2021 , Edited by admin on Sat Jun 26 10:27:41 UTC 2021
PRIMARY
DRUG BANK
DB05223
Created by admin on Sat Jun 26 10:27:41 UTC 2021 , Edited by admin on Sat Jun 26 10:27:41 UTC 2021
PRIMARY
INN
9386
Created by admin on Sat Jun 26 10:27:41 UTC 2021 , Edited by admin on Sat Jun 26 10:27:41 UTC 2021
PRIMARY
EPA CompTox
929016-96-6
Created by admin on Sat Jun 26 10:27:41 UTC 2021 , Edited by admin on Sat Jun 26 10:27:41 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
MAJOR
METABOLIC ENZYME -> SUBSTRATE
MAJOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC ORAL SINGLE DOSE ADMINISTRATION

Tmax PHARMACOKINETIC ORAL SINGLE DOSE ADMINISTRATION

blood-toplasma ratio PHARMACOKINETIC