RIBOCICLIB

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Synonyms
Status
Molecule Category Free-form
ATC L01EF02
UNII TK8ERE8P56

Structure

InChI Key RHXHGRAEPCAFML-UHFFFAOYSA-N
Smiles CN(C)C(=O)c1cc2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n1C1CCCC1
InChI
InChI=1S/C23H30N8O/c1-29(2)22(32)19-13-16-14-26-23(28-21(16)31(19)17-5-3-4-6-17)27-20-8-7-18(15-25-20)30-11-9-24-10-12-30/h7-8,13-15,17,24H,3-6,9-12H2,1-2H3,(H,25,26,27,28)

Physicochemical Descriptors

Property Name Value
Molecular Formula C23H30N8O
Molecular Weight 434.55
AlogP 2.8
Hydrogen Bond Acceptor 8.0
Hydrogen Bond Donor 2.0
Number of Rotational Bond 5.0
Polar Surface Area 91.21
Molecular species BASE
Aromatic Rings 3.0
Heavy Atoms 32.0

Bioactivity

Mechanism of Action Action Reference
Cyclin-dependent kinase 4 inhibitor INHIBITOR Other PubMed
Protein: Cyclin-dependent kinase 4
Description: Cyclin-dependent kinase 4
Organism : Homo sapiens
P11802 ENSG00000135446
Protein: Cyclin-dependent kinase 6
Description: Cyclin-dependent kinase 6
Organism : Homo sapiens
Q00534 ENSG00000105810
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Kinase Protein Kinase CMGC protein kinase group CMGC protein kinase CDK family CMGC protein kinase CDC2 subfamily
- 76000 - - -
Enzyme Kinase Protein Kinase CMGC protein kinase group CMGC protein kinase CDK family CMGC protein kinase CDK9 subfamily
- 197-3900 - - 84
Enzyme Kinase Protein Kinase CMGC protein kinase group
- 10-30 - - 101
Other cytosolic protein
- 10-30 - - 101
Assay Description Organism Bioactivity Reference
Inhibition of CDK4 (unknown origin) Homo sapiens 10.0 nM
Inhibition of CDK6 (unknown origin) Homo sapiens 39.0 nM
TR-FRET (Time-Resolved-Fluorescence Energy Transfer) Endpoint Assay: A 384-well microtiter Lance TR-FRET (time-resolved-fluorescence energy transfer) endpoint assay was used for CDK4/cyclin D1 kinase activity measurements. The same assay was used for IC50 determination of small molecule inhibitors. In general, the kinase reactions were carried out in 30 uL volumes in the reaction solution containing the following: 2 uL compound (in 20% DMSO), 18 uL CDK4/cyclin D1 in Assay Buffer (50 mM HEPES, pH 7.5, 5 mM MgCl2, 2 mM MnCl2, 1 mM DTT, 0.05% BSA, 0.02% Tween-20), 10 uL of the mixture of pRb152 and ATP. The final reaction mixture contains compound (inhibitor) with the concentration varying from 0.005-10 uM, 2% DMSO, 0.3 nM CDK4/cyclin D1, 175 nM pRb152, and 3 uM ATP (Amersham Pharmacia, Cat. No. 27-2056-01). All reactions were run at room temperature in 384-well white flat-bottom OptiPlates (Perkin Elmer, Cat. No. 6007290) for 60 min then were quenched by the addition of 10 uL of 120 mM EDTA. Homo sapiens 10.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 293.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 247.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 497.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 658.0 nM
Inhibition of recombinant human full length C-terminal 6His-tagged CDK9/Cyclin-T1 co-expressed in baculovirus infected sf21 cells using PDKtide substrate in presence of [gamma33P]ATP after 10 mins by scintillation counting method Homo sapiens 197.0 nM
Inhibition of recombinant human full length N-terminal GST-tagged CDK4/Cyclin-D3 co-expressed in baculovirus infected sf21 cells using Rb substrate in presence of [gamma33P]ATP after 10 mins by scintillation counting method Homo sapiens 13.0 nM
Inhibition of human CDK4/CyclinD3 by enzymatic radiometric assay Homo sapiens 13.0 nM
Inhibition of human CDK9/CyclinT1 by enzymatic radiometric assay Homo sapiens 197.0 nM
Antiproliferative activity against human KOPN8 cells after 72 hrs by CelTiter-Glo assay Homo sapiens 500.8 nM
Antiproliferative activity against human SEM cells after 72 hrs by CelTiter-Glo assay Homo sapiens 460.5 nM
Antiproliferative activity against human HepG2 cells after 72 hrs by CelTiter-Glo assay Homo sapiens 286.2 nM
Inhibition of CDK6/Cyclin-D3 (unknown origin) using histoneH1 as substrate after 90 mins by ADP-Glo assay Homo sapiens 28.0 nM
Inhibition of CDK4 (unknown origin) Homo sapiens 2.0 nM
Inhibition of CDK6 (unknown origin) Homo sapiens 6.0 nM
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Homo sapiens -12.64 %
Inhibition of GST-tagged CDK4/cyclin D1 (unknown origin) expressed in Baculovirus infected Sf9 cells using RPPTLSPIPHIPR peptide as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay Homo sapiens 30.0 nM
Inhibition of CDK4 (unknown origin) Homo sapiens 10.0 nM
Inhibition of CDK6 (unknown origin) Homo sapiens 39.0 nM
Inhibition of CDK4/CyclinD1 (unknown origin) assessed as reduction in retinoblastoma phosphorylation at S473 residue by ELISA Homo sapiens 10.0 nM
Inhibition of recombinant full-length human CDK4/cyclinD3 at 1 uM using Rb fragment as substrate measured after 40 mins in presence of [gamma33P]ATP by scintillation counting method relative to control Homo sapiens 101.0 %
Inhibition of recombinant full-length human CDK4/cyclinD3 using Rb fragment as substrate measured after 40 mins in presence of [gamma33P]ATP by scintillation counting method Homo sapiens 13.0 nM
Inhibition of recombinant full-length human CDK6/cyclinD3 at 1 uM using histone H1 as substrate measured after 40 mins in presence of [gamma33P]ATP by scintillation counting method relative to control Homo sapiens 86.0 %
Inhibition of recombinant full-length human CDK6/cyclinD3 using histone H1 as substrate measured after 40 mins in presence of [gamma33P]ATP by scintillation counting method Homo sapiens 71.0 nM
Inhibition of recombinant full-length human CDK9/cyclinT1 at 1 uM using KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC peptide as substrate measured after 40 mins in presence of [gamma33P]ATP by scintillation counting method relative to control Homo sapiens 84.0 %
Inhibition of recombinant full-length human CDK9/cyclinT1 using KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC peptide as substrate measured after 40 mins in presence of [gamma33P]ATP by scintillation counting method Homo sapiens 197.0 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 19.18 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 11.2 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.74 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 1.7 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 1.7 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.74 %
Inhibition of CDK6/cyclin D1 (unknown origin) Homo sapiens 19.5 nM
Inhibition of CDK4/cyclin D1 (unknown origin) Homo sapiens 22.5 nM
Inhibition of CDK6/Cyclin D (unknown origin) Homo sapiens 73.0 nM
Inhibition of CDK4/cyclin D1 (unknown origin) Homo sapiens 29.0 nM
Inhibition of human CDK4/cyclin D (unknown origin) using FAM-labeled peptide and ATP as substrate preincubated for 10 mins followed by substrate addition by mobility shift assay Homo sapiens 30.0 nM

Related Entries

Cross References

Resources Reference
ChEMBL CHEMBL3545110
DrugBank DB11730
DrugCentral 5218
FDA SRS TK8ERE8P56
Guide to Pharmacology 7383
PDB 6ZZ
PharmGKB PA166153470
PubChem 44631912
SureChEMBL SCHEMBL302310
ZINC ZINC000072316335
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