RUCAPARIB

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Synonyms
Status
Molecule Category Free-form
ATC L01XK03
UNII 8237F3U7EH
EPA CompTox DTXSID10182563

Structure

InChI Key HMABYWSNWIZPAG-UHFFFAOYSA-N
Smiles CNCc1ccc(-c2[nH]c3cc(F)cc4c3c2CCNC4=O)cc1
InChI
InChI=1S/C19H18FN3O/c1-21-10-11-2-4-12(5-3-11)18-14-6-7-22-19(24)15-8-13(20)9-16(23-18)17(14)15/h2-5,8-9,21,23H,6-7,10H2,1H3,(H,22,24)

Physicochemical Descriptors

Property Name Value
Molecular Formula C19H18FN3O
Molecular Weight 323.37
AlogP 2.98
Hydrogen Bond Acceptor 2.0
Hydrogen Bond Donor 3.0
Number of Rotational Bond 3.0
Polar Surface Area 56.92
Molecular species BASE
Aromatic Rings 3.0
Heavy Atoms 24.0

Bioactivity

Mechanism of Action Action Reference
PARP 1, 2 and 3 inhibitor INHIBITOR PubMed
Protein: PARP 1, 2 and 3
Description: Poly [ADP-ribose] polymerase 1
Organism : Homo sapiens
P09874 ENSG00000143799
Protein: PARP 1, 2 and 3
Description: Poly [ADP-ribose] polymerase 2
Organism : Homo sapiens
Q9UGN5 ENSG00000129484
Protein: PARP 1, 2 and 3
Description: Protein mono-ADP-ribosyltransferase PARP3
Organism : Homo sapiens
Q9Y6F1 ENSG00000041880
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Transferase
17 1-302 - 1-1 -
Assay Description Organism Bioactivity Reference
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: DYRK1A None 501.19 nM
SANGER: Inhibition of human COLO-800 cell growth in a cell viability assay. Homo sapiens 631.98 nM
SANGER: Inhibition of human MHH-ES-1 cell growth in a cell viability assay. Homo sapiens 500.56 nM
SANGER: Inhibition of human NB69 cell growth in a cell viability assay. Homo sapiens 945.52 nM
Inhibition of human N-terminal 6xhis-tagged ARTD6 (873 to 1161) expressed in Escherichia coli Rosetta2 (DE3) cells using NAD+ as substrate by fluorescence assay Homo sapiens 14.13 nM Inhibition of human N-terminal 6xhis-tagged ARTD6 (873 to 1161) expressed in Escherichia coli Rosetta2 (DE3) cells using NAD+ as substrate by fluorescence assay Homo sapiens 14.0 nM
Inhibition of human 6xhis-tagged ARTD5 (1030 to 1317) expressed in Escherichia coli Rosetta2 (DE3) cells using NAD+ as substrate by fluorescence assay Homo sapiens 25.12 nM Inhibition of human 6xhis-tagged ARTD5 (1030 to 1317) expressed in Escherichia coli Rosetta2 (DE3) cells using NAD+ as substrate by fluorescence assay Homo sapiens 25.0 nM
Inhibition of human full-length recombinant ARTD1 assessed as incorporation of [32P]NAD+ by scintillation counting analysis Homo sapiens 1.4 nM
In vivo inhibition of PARP activity in peripheral blood mononuclear cells of advanced solid tumor patient at 12 mg/m2 co-treated with rucaparib and temzolomide Homo sapiens 74.0 %
Inhibition of PARP1 (unknown origin) Homo sapiens 500.0 nM
Inhibition of PARP1 (unknown origin) Homo sapiens 0.8044 nM
Inhibition of human PARP1 using [3H]NAD as substrate after 1 min by microplate scintillation counting analysis Homo sapiens 1.98 nM
Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay Homo sapiens 4.69 nM
Cytotoxicity against BRCA2-deficient human Capan1 cells Homo sapiens 609.0 nM
Cytotoxicity against BRCA1-deficient human MX1 cells Homo sapiens 5.3 nM
Inhibition of full length recombinant human His6-tagged PARP1 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 3.162 nM Inhibition of full length recombinant human His6-tagged PARP1 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 3.2 nM
Inhibition of recombinant human His6-tagged PARP1 C-3-zinc finger domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 302.0 nM Inhibition of recombinant human His6-tagged PARP1 C-3-zinc finger domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 301.0 nM
Inhibition of recombinant human His6-tagged PARP1 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 39.81 nM Inhibition of recombinant human His6-tagged PARP1 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 39.8 nM
Inhibition of full length recombinant human His6-tagged PARP2 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 28.18 nM Inhibition of full length recombinant human His6-tagged PARP2 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 28.2 nM
Inhibition of recombinant human His6-tagged PARP2 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 138.04 nM Inhibition of recombinant human His6-tagged PARP2 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 138.0 nM
Inhibition of full length recombinant human His6-tagged PARP3 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 407.38 nM Inhibition of full length recombinant human His6-tagged PARP3 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 512.0 nM
Inhibition of recombinant human His6-tagged PARP4 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 839.0 nM Inhibition of recombinant human His6-tagged PARP4 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 831.76 nM
Inhibition of recombinant human TNKS1 ADP-ribosyltransferase/sterile alpha motif domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 144.0 nM Inhibition of recombinant human TNKS1 ADP-ribosyltransferase/sterile alpha motif domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 144.54 nM
Inhibition of recombinant human TNKS2 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 890.0 nM Inhibition of recombinant human TNKS2 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 891.25 nM
Inhibition of full length recombinant human His6-tagged PARP10 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 570.0 nM Inhibition of full length recombinant human His6-tagged PARP10 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay Homo sapiens 562.34 nM
Inhibition of recombinant human GST-tagged PARP1 expressed in Escherichia coli using damaged DNA as substrate after 30 mins in presence of NAD+ by resazurin dye based fluorescence assay Homo sapiens 26.0 nM
Inhibition of PARP1 (unknown origin) Homo sapiens 0.8 nM
Inhibition of PARP2 (unknown origin) Homo sapiens 0.5 nM
Inhibition of PARP1 (unknown origin) Homo sapiens 1.4 nM
Inhibition of human recombinant full-length PARP1 after 4 mins by [32P]NAD+ incorporation assay Homo sapiens 4.7 nM Inhibition of human recombinant full-length PARP1 after 4 mins by [32P]NAD+ incorporation assay Homo sapiens 1.4 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 98.35 %
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 0.49 % 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 0.49 %
Inhibition of N-terminal GST-tagged human full length PARP1 (2 to 1041 residues) expressed in baculovirus infected Sf9 cells using histone mixture (H2A and H2B) and biotinylated NAD+ as substrate in presence of activated DNA incubated for 60 mins by chemiluminescence assay Homo sapiens 0.7 nM Inhibition of N-terminal GST-tagged human full length PARP1 (2 to 1041 residues) expressed in baculovirus infected Sf9 cells using histone mixture (H2A and H2B) and biotinylated NAD+ as substrate in presence of activated DNA incubated for 60 mins by chemiluminescence assay Homo sapiens 1.4 nM
Inhibition of N-terminal GST-tagged human PARP2 (2 to 583 residues) expressed in baculovirus infected Sf9 cells using histone mixture (H2A and H2B) and biotinylated NAD+ as substrate in presence of activated DNA incubated for 60 mins by chemiluminescence assay Homo sapiens 0.8 nM Inhibition of N-terminal GST-tagged human PARP2 (2 to 583 residues) expressed in baculovirus infected Sf9 cells using histone mixture (H2A and H2B) and biotinylated NAD+ as substrate in presence of activated DNA incubated for 60 mins by chemiluminescence assay Homo sapiens 0.7 nM
Potentiation of anticancer activity against human MDA-MB-436 cells harboring BRCA mutant xenografted in SCID/nude mouse assessed as tumor growth inhibition at 3 mg/kg, po bid for 12 days co-administered with TMZ measured up to 9 weeks post-drug administration Homo sapiens 95.0 %
Potentiation of anticancer activity against human CAPAN-1 cells harboring BRCA mutant xenografted in SCID/nude mouse assessed as tumor growth inhibition at 3 mg/kg, po bid for 12 days co-administered with TMZ measured up to 9 weeks post-drug administration Homo sapiens 46.0 %
Potentiation of anticancer activity against human SK-ES-1 cells harboring EWSF1 translocation xenografted in SCID/nude mouse assessed as tumor growth inhibition at 3 mg/kg, po bid for 12 days co-administered with TMZ measured up to 9 weeks post drug administration Homo sapiens 20.62 %
Inhibition of human PARP-1 catalytic domain (662 to 1011 residues) expressed in Escherichia coli BL21(DE3) cells incubated for 0.5 hrs by fluorescence polarization assay based DNA trapping activity assay Homo sapiens 17.0 nM

Cross References

Resources Reference
ChEBI 134689
ChEMBL CHEMBL1173055
DrugBank DB12332
DrugCentral 5203
FDA SRS 8237F3U7EH
Guide to Pharmacology 7736
PDB RPB
PharmGKB PA166163418
PubChem 9931954
SureChEMBL SCHEMBL844585
ZINC ZINC000000025958
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