Details of the Drug

General Information of Drug (ID: DMCJLD1)

Drug Name
SCH 727965
Synonyms Dinaciclib; SCH-727965
Indication
Disease Entry ICD 11 Status REF
Acute lymphoblastic leukaemia 2A85 Discontinued in Phase 3 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 396.5
Logarithm of the Partition Coefficient (xlogp) 1.9
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C21H28N6O2
IUPAC Name
2-[(2S)-1-[3-ethyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidin-2-yl]ethanol
Canonical SMILES
CCC1=C2N=C(C=C(N2N=C1)NCC3=C[N+](=CC=C3)[O-])N4CCCC[C@H]4CCO
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
Cross-matching ID
PubChem CID
46926350
ChEBI ID
CHEBI:95060
CAS Number
779353-01-4
DrugBank ID
DB12021
TTD ID
D0D3PX
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Cyclin-dependent kinase 1 (CDK1) TTH6V3D CDK1_HUMAN Inhibitor [2]
Cyclin-dependent kinase 2 (CDK2) TT7HF4W CDK2_HUMAN Inhibitor [2]
Cyclin-dependent kinase 9 (CDK9) TT1LVF2 CDK9_HUMAN Inhibitor [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Breast cancer type 1 susceptibility protein (BRCA1) OT5BN6VH BRCA1_HUMAN Gene/Protein Processing [3]
Breast cancer type 2 susceptibility protein (BRCA2) OTF1XSV1 BRCA2_HUMAN Gene/Protein Processing [3]
Cyclin-dependent kinase 12 (CDK12) OTZUDGNU CDK12_HUMAN Gene/Protein Processing [3]
DNA repair protein RAD51 homolog 1 (RAD51) OTNVWGC1 RAD51_HUMAN Gene/Protein Processing [3]
Fanconi anemia group D2 protein (FANCD2) OTVEB5LF FACD2_HUMAN Gene/Protein Processing [3]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Protein Interaction/Cellular Processes [4]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Post-Translational Modifications [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Acute lymphoblastic leukaemia
ICD Disease Classification 2A85
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Cyclin-dependent kinase 1 (CDK1) DTT CDK1 5.27E-108 1.97 3.12
Cyclin-dependent kinase 2 (CDK2) DTT CDK2 2.28E-06 0.12 0.19
Cyclin-dependent kinase 9 (CDK9) DTT CDK9 4.38E-01 -0.04 -0.1
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: 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).
2 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
3 CDK12 Inhibition Reverses De Novo and Acquired PARP Inhibitor Resistance in BRCA Wild-Type and Mutated Models of Triple-Negative Breast Cancer. Cell Rep. 2016 Nov 22;17(9):2367-2381. doi: 10.1016/j.celrep.2016.10.077.
4 Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor. Mol Cancer Ther. 2010 Aug;9(8):2344-53. doi: 10.1158/1535-7163.MCT-10-0324. Epub 2010 Jul 27.