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Dinaciclib

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Also known as Mk-7965SCH 727965SCH-727965SCH727965DINACICLIB (SCH727965)Dinaciclip

Summary

Dinaciclib (CHEMBL2103840) is a phase-3 clinical-stage small-molecule EC 2.7.11.22 (cyclin-dependent kinase) inhibitor targeting CDK1, CDK2, and CDK5; indicated across 12 conditions including b-cell chronic lymphocytic leukemia and plasma cell myeloma.

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • Targets: 4 (CDK1, CDK2, CDK5…)
  • Indications: 12 conditions
  • Clinical trials: 18
  • Chemistry: 396.5 Da · C21H28N6O2

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL2103840
NameDinaciclib
TypeSmall molecule
Max phase3
FDA approvedno
PubChem CID46926350
ChEBICHEBI:95060
Molecular formulaC21H28N6O2
Molecular weight396.5
InChIKeyPIMQWRZWLQKKBJ-SFHVURJKSA-N

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

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

ChEBI definition: A pyrazolopyrimidine that is pyrazolo[1,5-a]pyrimidine substituted by ethyl, (2S)-2-(2-hydroxyethyl)piperidin-1-yl, and [(1-oxidopyridin-3-yl)methyl]amino groups at positions 3, 5, and 7, respectively. It is a potent pan-cyclin dependent kinase inhibitor that exhibits antineoplastic activity.

Pharmacological roles (ChEBI): EC 2.7.11.22 (cyclin-dependent kinase) inhibitor, antineoplastic agent, apoptosis inducer.

Also known as: Dinaciclib, Mk-7965, SCH 727965, SCH-727965, SCH727965, DINACICLIB, dinaciclib, DINACICLIB (SCH727965), Dinaciclib (SCH727965), Dinaciclip

Patent coverage: 900 distinct patent families (2,257 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 2,248 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
CDK1cyclin dependent kinase 1Inhibition8.52100% (common-essential)P06493
CDK2cyclin dependent kinase 2Inhibition8.771.1%P24941
CDK5cyclin dependent kinase 5Inhibition90.7%Q00535
CDK9cyclin dependent kinase 9Inhibition8.499.3% (common-essential)P50750

Broader ChEMBL bioactivity targets: 41 (assay-derived). Sample: Serine/threonine-protein kinase TAO2, Bromodomain-containing protein 4, Serine/threonine-protein kinase ICK, Bromodomain testis-specific protein, Cyclin-dependent kinase 13, Cyclin-dependent kinase 5/CDK5 activator 1, Cyclin-dependent kinase 4/cyclin D1, Cyclin-dependent kinase 1/cyclin B1, Cyclin-dependent kinase 2/cyclin E1, Cyclin-dependent kinase 2/cyclin E.

Bioactivity

ChEMBL activities: 154 potent at pChembl ≥ 5 of 159 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
CDK59IC501nMCHEMBL_ACT_16737083
CDK29IC501nMCHEMBL_ACT_16737084
CDK59IC501nMCHEMBL_ACT_16737208
CCNA29IC501nMCHEMBL_ACT_16737209
CDK29IC501nMCHEMBL_ACT_16844138
CDK59IC501nMCHEMBL_ACT_16844139
CDK29IC501nMCHEMBL_ACT_18299187
CDK59IC501nMCHEMBL_ACT_18299188
CDK59IC501nMCHEMBL_ACT_19016018
CDK29IC501nMCHEMBL_ACT_19016063
CDK29IC501nMCHEMBL_ACT_19027227
CDK59IC501nMCHEMBL_ACT_19027228
CDK29IC501nMCHEMBL_ACT_19258253
CDK59IC501nMCHEMBL_ACT_19258254
CDK29IC501nMCHEMBL_ACT_22758205
CDK59IC501nMCHEMBL_ACT_22758215
CDK29IC501nMCHEMBL_ACT_22930712
CDK59IC501nMCHEMBL_ACT_22930713
CDK29IC501nMCHEMBL_ACT_23159497
CDK19IC501nMCHEMBL_ACT_23297712
CDK29IC501nMCHEMBL_ACT_23297713
CDK49IC501nMCHEMBL_ACT_23297714
CDK59IC501nMCHEMBL_ACT_23297715
CDK99IC501nMCHEMBL_ACT_23297716
CDK59IC501nMCHEMBL_ACT_24759627
CDK49IC501nMCHEMBL_ACT_24788463
CDK19IC501nMCHEMBL_ACT_24788533
CDK29IC501nMCHEMBL_ACT_24788537
CDK59IC501nMCHEMBL_ACT_24788546
CDK29IC501nMCHEMBL_ACT_24975181

Target pathways

Aggregated over 4 target gene(s): CDK1, CDK2, CDK5, CDK9.

Top Reactome pathways

190 total, by targets touching each:

PathwayTargetsGenes
Signal Transduction4CDK1, CDK2, CDK5, CDK9
Generic Transcription Pathway4CDK1, CDK2, CDK5, CDK9
Transcriptional Regulation by TP534CDK1, CDK2, CDK5, CDK9
RNA Polymerase II Transcription4CDK1, CDK2, CDK5, CDK9
Gene expression (Transcription)4CDK1, CDK2, CDK5, CDK9
Disease3CDK2, CDK5, CDK9
Regulation of TP53 Activity3CDK1, CDK2, CDK5
Hemostasis2CDK2, CDK5
Developmental Biology2CDK2, CDK5
G0 and Early G12CDK1, CDK2
Cell Cycle2CDK1, CDK2
APC/C-mediated degradation of cell cycle proteins2CDK1, CDK2
Regulation of APC/C activators between G1/S and early anaphase2CDK1, CDK2
Mitotic G2-G2/M phases2CDK1, CDK2
Regulation of mitotic cell cycle2CDK1, CDK2
Mitotic G1 phase and G1/S transition2CDK1, CDK2
TP53 Regulates Transcription of Cell Cycle Genes2CDK1, CDK2
Regulation of TP53 Activity through Phosphorylation2CDK2, CDK5
Regulation of TP53 Degradation2CDK1, CDK2
Regulation of TP53 Expression and Degradation2CDK1, CDK2
G1/S Transition2CDK1, CDK2
Cyclin A/B1/B2 associated events during G2/M transition2CDK1, CDK2
G2/M Transition2CDK1, CDK2
Cell Cycle, Mitotic2CDK1, CDK2
G2/M Checkpoints2CDK1, CDK2
Cell Cycle Checkpoints2CDK1, CDK2
Factors involved in megakaryocyte development and platelet production2CDK2, CDK5
MAPK3 (ERK1) activation1CDK1
Opioid Signalling1CDK5
Formation of RNA Pol II elongation complex1CDK9

Dominant GO biological processes

GO termTargets
protein phosphorylation4
DNA repair3
DNA damage response3
cell division3
regulation of cell cycle3
G1/S transition of mitotic cell cycle2
G2/M transition of mitotic cell cycle2
microtubule cytoskeleton organization2
DNA replication2
apoptotic process2
cell migration2
negative regulation of protein ubiquitination2
positive regulation of DNA replication2
rhythmic process2
regulation of heterochromatin organization2

Indications & clinical

Indications

12 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
B-cell chronic lymphocytic leukemia3MONDO:0004948EFO:0000095
plasma cell myeloma2MONDO:0009693EFO:0001378
acute lymphoblastic leukemia2MONDO:0004967EFO:0000220
acute myeloid leukemia2MONDO:0018874EFO:0000222
melanoma1MONDO:0005105EFO:0000756
male breast carcinoma1MONDO:0005628EFO:0006861
neoplasm1MONDO:0005070EFO:0000616
prolymphocytic leukemia1MONDO:0001023MONDO:0001023
breast neoplasm1MONDO:0021100MONDO:0007254
exocrine pancreatic carcinoma1MONDO:0005192EFO:0002618
lymphoid leukemia1MONDO:0005402EFO:0004289
non-Hodgkin lymphoma1MONDO:0018908EFO:0005952

Clinical trials

Total trials: 18.

Phase distribution

PhaseTrials
PHASE110
PHASE25
PHASE1/PHASE22
PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT01580228PHASE3COMPLETEDA Phase 3 Study Comparing Dinaciclib Versus Ofatumumab in Patients With Refractory Chronic Lymphocytic Leukemia (P07714)
NCT00937937PHASE2ACTIVE_NOT_RECRUITINGDinaciclib in Treating Patients With Stage IV Melanoma
NCT00732810PHASE2COMPLETEDSCH 727965 in Patients With Advanced Breast and Lung Cancers (Study P04716)
NCT00798213PHASE2TERMINATEDSCH 727965 in Patients With Acute Myelogenous Leukemia and Acute Lymphoblastic Leukemia (P04717AM2)(TERMINATED)
NCT00871546PHASE2TERMINATEDSCH 727965 in Patients With Mantle Cell Lymphoma or B-Cell Chronic Lymphocytic Leukemia (Study P04715)
NCT01026324PHASE1/PHASE2TERMINATEDDinaciclib in Treating Patients With Stage III-IV Melanoma
NCT01096342PHASE2COMPLETEDDinaciclib in Treating Patients With Relapsed or Refractory Multiple Myeloma
NCT01515176PHASE1/PHASE2COMPLETEDOfatumumab and Dinaciclib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-Cell Prolymphocytic Leukemia
NCT01434316PHASE1ACTIVE_NOT_RECRUITINGVeliparib and Dinaciclib in Treating Patients With Advanced Solid Tumors
NCT00871663PHASE1COMPLETEDPhase 1 Weekly Dosing of SCH 727965 in Patients With Advanced Cancer (Study P04629AM6)
NCT00871910PHASE1COMPLETEDPhase 1 Every-3-Week Dosing of SCH 727965 in Patients With Advanced Cancer (Study P04630)
NCT01624441PHASE1COMPLETEDDinaciclib and Epirubicin Hydrochloride in Treating Patients With Metastatic Triple-Negative Breast Cancer
NCT01650727PHASE1COMPLETEDA Study of Dinaciclib in Combination With Rituximab in Participants With Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (P07974)
NCT01676753PHASE1COMPLETEDPhase 1b Trial of Dinaciclib With Pembrolizumab for Advanced Breast Cancer
NCT01711528PHASE1COMPLETEDDinaciclib, Bortezomib, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma
NCT01783171PHASE1COMPLETEDDinaciclib and Akt Inhibitor MK2206 in Treating Patients With Pancreatic Cancer That Cannot Be Removed by Surgery
NCT02684617PHASE1TERMINATEDStudy of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Hematologic Malignancies (MK-3475-155/KEYNOTE-155)
NCT03484520PHASE1TERMINATEDA Study of Venetoclax and Dinaciclib (MK7965) in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

96 molecules share ≥1 primary target. Top 60 by shared-target count:

MoleculeSourceStatusShared targets
ABEMACICLIBChEMBLPhase 4 (approved)CDK1, CDK2, CDK5, CDK9
PALBOCICLIBChEMBLPhase 4 (approved)CDK1, CDK2, CDK5, CDK9
ALVOCIDIBChEMBLPhase 3CDK1, CDK2, CDK5, CDK9
CRENOLANIBChEMBLPhase 3CDK1, CDK2, CDK5, CDK9
DEFACTINIBChEMBLPhase 3CDK1, CDK2, CDK5, CDK9
AT-7519ChEMBLPhase 2CDK1, CDK2, CDK5, CDK9
CT-7001ChEMBLPhase 2CDK1, CDK2, CDK5, CDK9
CULMERCICLIBChEMBLPhase 2CDK1, CDK2, CDK5, CDK9
CYC-065ChEMBLPhase 2CDK1, CDK2, CDK5, CDK9
INDIRUBINChEMBLPhase 2CDK1, CDK2, CDK5, CDK9
ISTISOCICLIBChEMBLPhase 2CDK1, CDK2, CDK5, CDK9
MILCICLIBChEMBLPhase 2CDK1, CDK2, CDK5, CDK9
NARAZACICLIBChEMBLPhase 2CDK1, CDK2, CDK5, CDK9
RG-547ChEMBLPhase 2CDK1, CDK2, CDK5, CDK9
SELICICLIBChEMBLPhase 2CDK1, CDK2, CDK5, CDK9
VORUCICLIBChEMBLPhase 2CDK1, CDK2, CDK5, CDK9
ZEMIRCICLIBChEMBLPhase 2CDK1, CDK2, CDK5, CDK9
ZOTIRACICLIBChEMBLPhase 2CDK1, CDK2, CDK5, CDK9
AfatinibPubChemApprovedCDK1, CDK2, CDK5, CDK9
BinimetinibPubChemApprovedCDK1, CDK2, CDK5, CDK9
CrizotinibPubChemApprovedCDK1, CDK2, CDK5, CDK9
dacomitinibPubChemApprovedCDK1, CDK2, CDK5, CDK9
FostamatinibPubChemApprovedCDK1, CDK2, CDK5, CDK9
IdelalisibPubChemApprovedCDK1, CDK2, CDK5, CDK9
PazopanibPubChemApprovedCDK1, CDK2, CDK5, CDK9
regorafenibPubChemApprovedCDK1, CDK2, CDK5, CDK9
SelumetinibPubChemApprovedCDK1, CDK2, CDK5, CDK9
TrametinibPubChemApprovedCDK1, CDK2, CDK5, CDK9
DABRAFENIBChEMBLPhase 4 (approved)CDK1, CDK2, CDK5
LESTAURTINIBChEMBLPhase 3CDK2, CDK5, CDK9
QUERCETINChEMBLPhase 3CDK1, CDK2, CDK5
ASNUCICLIBChEMBLPhase 2CDK1, CDK2, CDK9
CENISERTIBChEMBLPhase 2CDK1, CDK2, CDK5
EBVACICLIBChEMBLPhase 2CDK1, CDK2, CDK9
FISETINChEMBLPhase 2CDK1, CDK2, CDK5
INIXACICLIBChEMBLPhase 2CDK2, CDK5, CDK9
LUTEOLINChEMBLPhase 2CDK1, CDK2, CDK5
LY-2090314ChEMBLPhase 2CDK1, CDK2, CDK5
R-406ChEMBLPhase 2CDK1, CDK2, CDK5
REBASTINIBChEMBLPhase 2CDK1, CDK2, CDK5
RIVICICLIBChEMBLPhase 2CDK1, CDK2, CDK9
RONICICLIBChEMBLPhase 2CDK1, CDK2, CDK9
SILMITASERTIBChEMBLPhase 2CDK1, CDK2, CDK5
SOTRASTAURINChEMBLPhase 2CDK1, CDK2, CDK5
TEGTOCICLIBChEMBLPhase 2CDK1, CDK2, CDK9
BelzutifanPubChemApprovedCDK1, CDK5, CDK9
GefitinibPubChemApprovedCDK1, CDK5, CDK9
MOMELOTINIBChEMBLPhase 4 (approved)CDK2, CDK9
PACRITINIBChEMBLPhase 4 (approved)CDK2, CDK9
RIBOCICLIBChEMBLPhase 4 (approved)CDK2, CDK9
SORAFENIBChEMBLPhase 4 (approved)CDK2, CDK5
TRILACICLIBChEMBLPhase 4 (approved)CDK2, CDK9
6-O-BENZYLGUANINEChEMBLPhase 3CDK1, CDK2
ENZASTAURINChEMBLPhase 3CDK2, CDK9
FASUDILChEMBLPhase 3CDK5, CDK9
LEROCICLIBChEMBLPhase 3CDK2, CDK9
LINIFANIBChEMBLPhase 3CDK1, CDK9
AT-9283ChEMBLPhase 2CDK5, CDK9
CROZBACICLIBChEMBLPhase 2CDK1, CDK2
LAUROGUADINEChEMBLPhase 2CDK1, CDK2

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot