Drug Information

Drug General Information
Drug ID
D0D3PX
Former ID
DCL001081
Drug Name
SCH 727965
Synonyms
Dinaciclib; SCH-727965
Drug Type
Small molecular drug
Indication Acute lymphoblastic leukemia [ICD9: 204.0, 556; ICD10:C91.0] Discontinued in Phase 3 [1], [2], [3]
Company
Schering-Plough
Structure
Download
2D MOL

3D MOL
Formula
C21H28N6O2
InChI
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
InChIKey
PIMQWRZWLQKKBJ-SFHVURJKSA-N
PubChem Compound ID
46926350
PubChem Substance ID
99431612, 120930394, 124490344, 131407186, 134339476, 135264288, 136345849, 136367504, 136920416, 141002406, 152159564, 152258233, 160647069, 160692470, 162011589, 162205183, 172131336, 172918929, 174530706, 178103951, 185972567, 189622864, 198972887, 223387655, 223405957, 223681485, 223705097, 237165571, 242744373, 251910607, 251971097, 252110195, 252160440, 252215289, 252451690
Target and Pathway
Target(s) Cell division protein kinase 9 Target Info Inhibitor [4]
Cell division protein kinase 2 Target Info Inhibitor [4]
Cell division control protein 2 homolog Target Info Inhibitor [4]
KEGG Pathway Transcriptional misregulation in cancerhsa04068:FoxO signaling pathway
Cell cycle
Oocyte meiosis
p53 signaling pathway
PI3K-Akt signaling pathway
Progesterone-mediated oocyte maturation
Hepatitis B
Measles
Herpes simplex infection
Epstein-Barr virus infection
Pathways in cancer
Viral carcinogenesis
Prostate cancer
Small cell lung cancerhsa04110:Cell cycle
Gap junction
NetPath Pathway EGFR1 Signaling PathwayNetPath_11:TCR Signaling PathwayNetPath_21:RANKL Signaling Pathway
PANTHER Pathway p53 pathway
p53 pathway feedback loops 2
Pathway Interaction Database Regulation of nuclear SMAD2/3 signaling
Signaling events mediated by PRL
p73 transcription factor network
E2F transcription factor network
ATR signaling pathway
mTOR signaling pathway
IL2-mediated signaling events
FoxO family signaling
FOXM1 transcription factor network
BARD1 signaling events
p53 pathway
Regulation of retinoblastoma proteinp73pathway:p73 transcription factor network
PLK1 signaling events
AP-1 transcription factor network
Retinoic acid receptors-mediated signaling
Reactome SMAD2/SMAD3:SMAD4 heterotrimer regulates transcriptionR-HSA-1538133:G0 and Early G1
Activation of ATR in response to replication stress
Regulation of APC/C activators between G1/S and early anaphase
SCF(Skp2)-mediated degradation of p27/p21
Senescence-Associated Secretory Phenotype (SASP)
DNA Damage/Telomere Stress Induced Senescence
Processing of DNA double-strand break ends
G2 Phase
Orc1 removal from chromatin
Cyclin E associated events during G1/S transition
Cyclin A/B1 associated events during G2/M transition
p53-Dependent G1 DNA Damage Response
Cyclin A:Cdk2-associated events at S phase entry
Meiotic recombination
Factors involved in megakaryocyte development and platelet productionR-HSA-110056:MAPK3 (ERK1) activation
E2F mediated regulation of DNA replication
G0 and Early G1
Cyclin B2 mediated events
Golgi Cisternae Pericentriolar Stack Reorganization
Cdc20:Phospho-APC/C mediated degradation of Cyclin A
Phosphorylation of the APC/C
Phosphorylation of Emi1
Condensation of Prophase Chromosomes
MASTL Facilitates Mitotic Progression
Resolution of Sister Chromatid Cohesion
Condensation of Prometaphase Chromosomes
Regulation of PLK1 Activity at G2/M Transition
Activation of NIMA Kinases NEK9, NEK6, NEK7
Loss of Nlp from mitotic centrosomes
Recruitment of mitotic centrosome proteins and complexes
Loss of proteins required for interphase microtubule organization?from the centrosome
Recruitment of NuMA to mitotic centrosomes
Depolymerisation of the Nuclear Lamina
Anchoring of the basal body to the plasma membrane
MAPK6/MAPK4 signaling
G1/S-Specific Transcription
G2/M DNA replication checkpoint
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
WikiPathways Cardiac Hypertrophic Response
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
Host Interactions of HIV factors
HIV Life Cycle
IL-9 Signaling Pathway
RNA Polymerase II Transcription
MicroRNAs in cardiomyocyte hypertrophyWP707:DNA Damage Response
ID signaling pathway
DNA Replication
G1 to S cell cycle control
M/G1 Transition
S Phase
Meiotic Recombination
Aryl Hydrocarbon Receptor
ATM Signaling Pathway
Retinoblastoma (RB) in Cancer
Spinal Cord Injury
Integrated Pancreatic Cancer Pathway
Oncostatin M Signaling Pathway
Prostate Cancer
Signaling Pathways in Glioblastoma
TSH signaling pathway
Integrated Breast Cancer Pathway
Integrated Cancer pathway
Synthesis of DNA
Regulation of DNA replication
Mitotic G2-G2/M phases
Mitotic G1-G1/S phases
Factors involved in megakaryocyte development and platelet production
Cell Cycle
APC/C-mediated degradation of cell cycle proteins
Cell Cycle Checkpoints
miRNA Regulation of DNA Damage ResponseWP707:DNA Damage Response
TGF beta Signaling Pathway
PPAR Alpha Pathway
MAP kinase activation in TLR cascade
RAF/MAP kinase cascade
Mitotic Prophase
Mitotic Prometaphase
BMI1
Regulation of Microtubule Cytoskeleton
miRNA Regulation of DNA Damage Response
References
REF 1Cyclin-dependent kinase inhibitor Dinaciclib (SCH727965) inhibits pancreatic cancer growth and progression in murine xenograft models. Cancer Biol Ther. 2011 Oct 1;12(7):598-609. Epub 2011 Oct 1.
REF 2Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma. Blood. 2015 Jan 15;125(3):443-8.
REF 3(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7379).
REF 4Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.

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