DINACICLIB

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 Search

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
Sources: http://adisinsight.springer.com/drugs/800026277
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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclin-dependent kinase 1 27 Target ID: CHEMBL308 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20663931	Inhibitor 8297	3.0 nM [IC50]
Cyclin-dependent kinase 2 22 Target ID: CHEMBL301 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20663931	Inhibitor 8297	1.0 nM [IC50]
Cyclin-dependent kinase 5 8 Target ID: CHEMBL4036 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20663931	Inhibitor 8297	1.0 nM [IC50]
Cyclin-dependent kinase 9 19 Target ID: CHEMBL3116 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20663931	Inhibitor 8297	4.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Chronic lymphocytic leukemia 59 Sources: http://adisinsight.springer.com/drugs/800026277	Primary	Phase III 656	Unknown Approved Use Unknown
Melanoma 88 Sources: http://adisinsight.springer.com/drugs/800026277	Primary	Phase II 1132	Unknown Approved Use Unknown
Breast cancer 434 Sources: http://adisinsight.springer.com/drugs/800026277	Primary	Phase II 1132	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: http://adisinsight.springer.com/drugs/800026277	Primary	Phase II 1132	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 Page: p.1260	DLT: Pancytopenia, Pneumonia... Dose limiting toxicities: Pancytopenia (25%) Pneumonia (25%) Neutropenic fever (25%) Sources: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/25395429	unhealthy, ADULT n = 15 Health Status: unhealthy Condition: multiple myeloma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/25395429	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: https://pubmed.ncbi.nlm.nih.gov/25395429
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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 Page: p.1261	DLT: Neutropenic fever, Neutropenia... Dose limiting toxicities: Neutropenic fever (50%) Neutropenia (50%) Sources: https://pubmed.ncbi.nlm.nih.gov/28859059 Page: p.1261

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/25395429	unhealthy, ADULT n = 15 Health Status: unhealthy Condition: multiple myeloma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/25395429
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: https://pubmed.ncbi.nlm.nih.gov/25395429	unhealthy, ADULT n = 15 Health Status: unhealthy Condition: multiple myeloma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/25395429
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: https://pubmed.ncbi.nlm.nih.gov/25395429	unhealthy, ADULT n = 15 Health Status: unhealthy Condition: multiple myeloma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/25395429
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: https://pubmed.ncbi.nlm.nih.gov/25395429	unhealthy, ADULT n = 15 Health Status: unhealthy Condition: multiple myeloma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/25395429
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: https://pubmed.ncbi.nlm.nih.gov/25395429	unhealthy, ADULT n = 15 Health Status: unhealthy Condition: multiple myeloma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/25395429
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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 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: https://pubmed.ncbi.nlm.nih.gov/28859059 Page: p.1261

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P003B0P	https://www.1pchem.com/search?query=1P003B0P
AChemBlock	P51693	http://www.achemblock.com/catalogsearch/result/?q=P51693
AK Scientific	SYN5716	https://aksci.com/item_detail.php?cat=SYN5716
AK Scientific	Y0347	https://aksci.com/item_detail.php?cat=Y0347
AOBIOUS INC	AOB87336	http://aobious.com/aobious/search?search_query=AOB87336
ApexBio Technology	A8412	https://www.apexbt.com/catalogsearch/result/?q=A8412
AstaTech	40210	http://astatechinc.com/CPSResult.php?CRNO=40210
Axon MedChem	1776	https://www.axonmedchem.com/product/1776
BLD Pharm	BD630863	http://www.bldpharm.com/search/Search.html?keyword=BD630863
BOC Sciences	779353-01-4	http://www.bocsci.com/description.asp?cas=779353-01-4
BioSynth	J-501008	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/J-501008
Cayman Chemical	14707	http://www.caymanchem.com/app/template/Product.vm/catalog/14707
Chem Scene	CS-0541	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0541
ChemShuttle	111884	https://www.chemshuttle.com/catalogsearch/result/?q=111884
Hairui	DIXM014	http://www.hairuichem.com/en/product/search.do?q=DIXM014
KeyOrganics	AS-17017	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17017
Lab Network	LN01296654	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01296654
Matrix Scientific	147226	http://www.matrixscientific.com/147226.html
MedChem Express	HY-10492	https://www.medchemexpress.com/search.html?q=HY-10492&ft=&fa=&fp=
MolPort	MolPort-023-293-537	https://www.molport.com/shop/molecule-link/MolPort-023-293-537
Molnova	M15942	https://www.molnova.com/en/serch-list.html?keywords=M15942
ShangHai Biochempartner	BCP000492	http://www.biochempartner.com/search_BCP000492
TargetMol	T1912	https://www.targetmol.com/search?keyword=T1912
Toronto Research Chemicals	B680677	https://www.trc-canada.com/product-detail/?CatNum=B680677
Toronto Research Chemicals	D479725	https://www.trc-canada.com/product-detail/?CatNum=D479725
eMolecules	108760520	https://orderbb.emolecules.com/search/#?query=108760520
eMolecules	300651804	https://orderbb.emolecules.com/search/#?query=300651804
eMolecules	42777432	https://orderbb.emolecules.com/search/#?query=42777432
eNovation Chemicals	D522268	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D522268&searchbtn.x=0&searchbtn.y=0

PubMed

Title	Date	PubMed
Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor.	2010 Aug	20663931
Discovery of Dinaciclib (SCH 727965): A Potent and Selective Inhibitor of Cyclin-Dependent Kinases.	2010 Aug 12	24900195
The landscape of somatic copy-number alteration across human cancers.	2010 Feb 18	20164920
A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma.	2010 Jul 13	20609353
Therapeutic response to CDK4/6 inhibition in breast cancer defined by ex vivo analyses of human tumors.	2012 Jul 15	22767154
Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia.	2012 Oct 16	23079656
The requirement for cyclin D function in tumor maintenance.	2012 Oct 16	23079655
A CDK4/6 inhibitor enhances cytotoxicity of paclitaxel in lung adenocarcinoma cells harboring mutant KRAS as well as wild-type KRAS.	2013 Jul	23792647
Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains.	2013 Nov 15	24007471
Dinaciclib Induces Anaphase Catastrophe in Lung Cancer Cells via Inhibition of Cyclin-Dependent Kinases 1 and 2.	2016 Nov	27550941
Pro-survival signal inhibition by CDK inhibitor dinaciclib in Chronic Lymphocytic Leukaemia.	2016 Nov	27469405

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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

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Name

Type

Language

DINACICLIB

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