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

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H28N6O2
Molecular Weight 396.486
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DINACICLIB

SMILES

CCC1=C2N=C(C=C(NCC3=C[N+]([O-])=CC=C3)N2N=C1)N4CCCC[C@H]4CCO

InChI

InChIKey=PIMQWRZWLQKKBJ-SFHVURJKSA-N
InChI=1S/C21H28N6O2/c1-2-17-14-23-27-19(22-13-16-6-5-9-25(29)15-16)12-20(24-21(17)27)26-10-4-3-7-18(26)8-11-28/h5-6,9,12,14-15,18,22,28H,2-4,7-8,10-11,13H2,1H3/t18-/m0/s1

HIDE SMILES / InChI

Molecular Formula C21H28N6O2
Molecular Weight 396.486
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20663931 https://www.ncbi.nlm.nih.gov/pubmed/25349887

Dinaciclib (SCH 727965) is a small molecule inhibitor of cyclin-dependent kinases. Dinaciclib demostrates potent and selective inhibition of CDK2, CDK5, CDK1, and CDK9 activity. Dinaciclib inhibits cell cycle progression and proliferation in various tumor cell lines in vitro. Dinaciclib is a product of a drug discovery collaboration between Pharmacopeia (later Ligand Pharmaceuticals) and Schering-Plough (later Merck & Co.) that began in 1998. Dinaciclib showed promising effect in treating haematological malignancies and solid tumors.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
3.0 nM [IC50]
1.0 nM [IC50]
1.0 nM [IC50]
4.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
58 mg/m2 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 58 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 58 mg/m2, 1 times / 3 weeks
Sources: Page: p.1260
unhealthy, ADULT
n = 4
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources: Page: p.1260
DLT: Pancytopenia, Pneumonia...
Dose limiting toxicities:
Pancytopenia (25%)
Pneumonia (25%)
Neutropenic fever (25%)
Sources: Page: p.1260
50 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 50 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 50 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, ADULT
n = 15
Health Status: unhealthy
Condition: multiple myeloma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 15
Sources:
Other AEs: Thrombocytopenia, Leukopenia...
Other AEs:
Thrombocytopenia (grade 4, 6.7%)
Leukopenia (grade 4, 6.7%)
Neutropenia (grade 4, 6.7%)
Diarrhea (grade 4, 6.7%)
Vision blurred (grade 4, 6.7%)
Sources:
50 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 50 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 50 mg/m2, 1 times / 3 weeks
Sources: Page: p.1260
unhealthy, ADULT
n = 15
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 15
Sources: Page: p.1260
DLT: Arterial hypotension, Blood uric acid increased...
Dose limiting toxicities:
Arterial hypotension (6.7%)
Blood uric acid increased (6.7%)
ALT increased (6.7%)
AST increased (13.3%)
Sources: Page: p.1260
50 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 50 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 50 mg/m2, 1 times / 3 weeks
Sources: Page: p.1261
unhealthy, ADULT
n = 2
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2
Sources: Page: p.1261
DLT: Neutropenic fever, Neutropenia...
Dose limiting toxicities:
Neutropenic fever (50%)
Neutropenia (50%)
Sources: Page: p.1261
AEs

AEs

AESignificanceDosePopulation
Neutropenic fever 25%
DLT
58 mg/m2 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 58 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 58 mg/m2, 1 times / 3 weeks
Sources: Page: p.1260
unhealthy, ADULT
n = 4
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources: Page: p.1260
Pancytopenia 25%
DLT
58 mg/m2 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 58 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 58 mg/m2, 1 times / 3 weeks
Sources: Page: p.1260
unhealthy, ADULT
n = 4
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources: Page: p.1260
Pneumonia 25%
DLT
58 mg/m2 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 58 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 58 mg/m2, 1 times / 3 weeks
Sources: Page: p.1260
unhealthy, ADULT
n = 4
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources: Page: p.1260
Diarrhea grade 4, 6.7%
50 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 50 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 50 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, ADULT
n = 15
Health Status: unhealthy
Condition: multiple myeloma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 15
Sources:
Leukopenia grade 4, 6.7%
50 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 50 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 50 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, ADULT
n = 15
Health Status: unhealthy
Condition: multiple myeloma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 15
Sources:
Neutropenia grade 4, 6.7%
50 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 50 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 50 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, ADULT
n = 15
Health Status: unhealthy
Condition: multiple myeloma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 15
Sources:
Thrombocytopenia grade 4, 6.7%
50 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 50 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 50 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, ADULT
n = 15
Health Status: unhealthy
Condition: multiple myeloma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 15
Sources:
Vision blurred grade 4, 6.7%
50 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 50 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 50 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, ADULT
n = 15
Health Status: unhealthy
Condition: multiple myeloma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 15
Sources:
AST increased 13.3%
DLT
50 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 50 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 50 mg/m2, 1 times / 3 weeks
Sources: Page: p.1260
unhealthy, ADULT
n = 15
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 15
Sources: Page: p.1260
ALT increased 6.7%
DLT
50 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 50 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 50 mg/m2, 1 times / 3 weeks
Sources: Page: p.1260
unhealthy, ADULT
n = 15
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 15
Sources: Page: p.1260
Arterial hypotension 6.7%
DLT
50 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 50 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 50 mg/m2, 1 times / 3 weeks
Sources: Page: p.1260
unhealthy, ADULT
n = 15
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 15
Sources: Page: p.1260
Blood uric acid increased 6.7%
DLT
50 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 50 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 50 mg/m2, 1 times / 3 weeks
Sources: Page: p.1260
unhealthy, ADULT
n = 15
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 15
Sources: Page: p.1260
Neutropenia 50%
DLT, Disc. AE
50 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 50 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 50 mg/m2, 1 times / 3 weeks
Sources: Page: p.1261
unhealthy, ADULT
n = 2
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2
Sources: Page: p.1261
Neutropenic fever 50%
DLT, Disc. AE
50 mg/m2 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 50 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 50 mg/m2, 1 times / 3 weeks
Sources: Page: p.1261
unhealthy, ADULT
n = 2
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2
Sources: Page: p.1261
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
The landscape of somatic copy-number alteration across human cancers.
2010 Feb 18
Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains.
2013 Nov 15
Inhibition of cyclin dependent kinase 9 by dinaciclib suppresses cyclin B1 expression and tumor growth in triple negative breast cancer.
2016 Aug 30
Patents

Sample Use Guides

The maximum administered dose was found to be 14 mg/m2 and the recommended phase 2 dose was determined to be 12 mg/m2. Dinaciclib administered every week for 3 weeks (on days 1, 8, and 15 of a 28-day cycle) was generally safe and well tolerated.
Route of Administration: Intravenous
Asynchronously growing A2780 cells exposed to 125 to 250 nmol/L Dinaciclib (SCH 727965) for 2 hours partially suppressed DNA synthesis and BrdUrd incorporation for 24 hours. Higher exposures (≤500 nmol/L) were sufficient to completely suppress DNA synthesis for 24 hours and were correlated with the accumulation of apoptotic (sub-G1) cells.
Substance Class Chemical
Created
by admin
on Fri Dec 15 17:30:41 GMT 2023
Edited
by admin
on Fri Dec 15 17:30:41 GMT 2023
Record UNII
4V8ECV0NBQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DINACICLIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
Dinaciclib [WHO-DD]
Common Name English
SCH727965
Code English
3-[[[3-Ethyl-5-[(2S)-2-(2-hydroxyethyl)piperidin-1-yl]pyrazolo[1,5-a]pyrimidin-7-yl]amino]methyl]pyridine 1-oxide
Systematic Name English
DINACICLIB [USAN]
Common Name English
SCH-727965
Code English
dinaciclib [INN]
Common Name English
2-PIPERIDINEETHANOL, 1-(3-ETHYL-7-(((1-OXIDO-3-PYRIDINYL)METHYL)AMINO)PYRAZOLO(1,5- A)PYRIMIDIN-5-YL)-, (2S)-
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C2185
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
FDA ORPHAN DRUG 347211
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
NCI_THESAURUS C129825
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
EU-Orphan Drug EU/3/11/901
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
Code System Code Type Description
MESH
C553669
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
PRIMARY
NCI_THESAURUS
C78854
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
PRIMARY
EPA CompTox
DTXSID90999131
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
PRIMARY
WIKIPEDIA
Dinaciclib
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
PRIMARY
SMS_ID
100000134800
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
PRIMARY
USAN
UU-88
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
PRIMARY
ChEMBL
CHEMBL2103840
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
PRIMARY
CAS
779353-01-4
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
PRIMARY
DRUG BANK
DB12021
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
PRIMARY
FDA UNII
4V8ECV0NBQ
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
PRIMARY
EVMPD
SUB64819
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
PRIMARY
PUBCHEM
46926350
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
PRIMARY
INN
9157
Created by admin on Fri Dec 15 17:30:42 GMT 2023 , Edited by admin on Fri Dec 15 17:30:42 GMT 2023
PRIMARY
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