TALAZOPARIB

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Synonyms
Status
Molecule Category Free-form
ATC L01XK04
UNII 9QHX048FRV

Structure

InChI Key HWGQMRYQVZSGDQ-HZPDHXFCSA-N
Smiles Cn1ncnc1[C@H]1c2n[nH]c(=O)c3cc(F)cc(c23)N[C@@H]1c1ccc(F)cc1
InChI
InChI=1S/C19H14F2N6O/c1-27-18(22-8-23-27)15-16(9-2-4-10(20)5-3-9)24-13-7-11(21)6-12-14(13)17(15)25-26-19(12)28/h2-8,15-16,24H,1H3,(H,26,28)/t15-,16-/m1/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C19H14F2N6O
Molecular Weight 380.36
AlogP 2.63
Hydrogen Bond Acceptor 6.0
Hydrogen Bond Donor 2.0
Number of Rotational Bond 2.0
Polar Surface Area 88.49
Molecular species NEUTRAL
Aromatic Rings 4.0
Heavy Atoms 28.0

Bioactivity

Mechanism of Action Action Reference
Poly [ADP-ribose] polymerase 2 inhibitor INHIBITOR PubMed
Protein: Poly [ADP-ribose] polymerase-1
Description: Poly [ADP-ribose] polymerase 1
Organism : Homo sapiens
P09874 ENSG00000143799
Protein: Poly [ADP-ribose] polymerase 2
Description: Poly [ADP-ribose] polymerase 2
Organism : Homo sapiens
Q9UGN5 ENSG00000129484
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Transferase
3-3 1-7 - 1-1 91
Assay Description Organism Bioactivity Reference
Inhibition of PARP1 (unknown origin) Homo sapiens 0.6 nM
Inhibition of PARP in human LoVo cells assessed as inhibition of hydrogen peroxide-induced PARylation treated for 30 mins prior to incubation with H2O2 for 5 mins by fluorescence analysis Homo sapiens 2.5 nM
Inhibition of CYP2C19 (unknown origin) at 10 uM Homo sapiens 12.0 %
Inhibition of CYP2C9 (unknown origin) at 10 uM Homo sapiens 12.0 %
Inhibition of CYP2D6 (unknown origin) at 10 uM Homo sapiens 12.0 %
Inhibition of CYP3A4 (unknown origin) at 10 uM Homo sapiens 12.0 %
Inhibition of CYP1A2 (unknown origin) at 10 uM Homo sapiens 12.0 %
Inhibition of human PARP1 using [3H]NAD as substrate after 1 min by microplate scintillation counting analysis Homo sapiens 0.57 nM Inhibition of human PARP1 using [3H]NAD as substrate after 1 min by microplate scintillation counting analysis Homo sapiens 1.2 nM
Inhibition of human PARP2 using [3H]NAD as substrate after 1 min by microplate scintillation counting analysis Homo sapiens 0.85 nM
Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay Homo sapiens 2.51 nM
Cytotoxicity against BRCA2-deficient human Capan1 cells Homo sapiens 5.0 nM
Cytotoxicity against BRCA1-deficient human MX1 cells Homo sapiens 0.3 nM
Cytotoxicity against human MRC5 cells Homo sapiens 310.0 nM
Inhibition of PARP1 (unknown origin) by ELISA Homo sapiens 7.2 nM
Antiproliferative activity against human MDA-MB-436 cells after 7 days by CCK8 or SRB assay Homo sapiens 0.7 nM
Cytotoxicity against BRCA2 deficient Chinese hamster VC8 cells after 3 days by CCK8 or SRB assay Cricetulus griseus 4.2 nM
Antiproliferative activity against human Capan1 cells after 7 days by CCK8 or SRB assay Homo sapiens 1.8 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 4.62 %
Cytotoxicity against BRCA1-proficient human SUM149 cells measured after 6 days by microscopic analysis Homo sapiens 23.2 nM
Cytotoxicity against BRCA1-deficient human SUM149 cells measured after 6 days by microscopic analysis Homo sapiens 1.6 nM
Inhibition of PARP1 (unknown origin) Homo sapiens 0.58 nM
Inhibition of PARP1 (unknown origin) after 1 min in presence of NAD by top count analysis Homo sapiens 1.2 nM Inhibition of PARP1 (unknown origin) after 1 min in presence of NAD by top count analysis Homo sapiens 0.57 nM
Inhibition of PARP2 (unknown origin) after 1 min in presence of NAD by top count analysis Homo sapiens 0.9 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 20.59 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 15.89 %
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 -0.08 % 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 -0.25 % 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 -0.25 % 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 -0.08 %
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 1.0 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 0.6 nM
Inhibition of PARP1 in human MDA-MB-436 cells assessed as inhibition of PARylation at 10 nM incubated for 1 hr by chemiluminescence assay Homo sapiens 91.0 %
Cytotoxicity against human MDA-MB-436 cells assessed as inhibition of cell viability incubated for 4 days by CellTiterGlo luminescence assay Homo sapiens 0.38 nM
Cytotoxicity against human MDA-MB-436 cells assessed as inhibition of cell viability incubated for 14 days with three intermittent intervals by CellTiterGlo luminescence assay Homo sapiens 0.012 nM
Cytotoxicity against HEK293 cells assessed as inhibition of cell viability Homo sapiens 4.95 nM
Anticancer activity against human MDA-MB-436 cells harboring BRCA mutant xenografted in SCID/nude mouse assessed as tumor growth regression at 0.15 mg/kg, po bid and measured up to 5 weeks post-drug administration Homo sapiens 65.0 %
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 3.2 nM

Cross References

Resources Reference
ChEMBL CHEMBL3137320
DrugBank DB11760
DrugCentral 5300
FDA SRS 9QHX048FRV
Guide to Pharmacology 8313
PDB 2YQ
PubChem 135565082
SureChEMBL SCHEMBL2299348
ZINC ZINC000072318110
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