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Talazoparib [1207456-01-6]

Imprimer

Référence HY-16106-5mg

Conditionnement : 5mg

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Marque : MedChemExpress

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Description

Talazoparib (BMN-673) is a highly potent, orally active PARP1/2 inhibitor.Talazoparib inhibits PARP1 and PARP2 enzyme activity with K_is of 1.2 nM and 0.87 nM, respectively. Talazoparib has antitumor activity^[1].

IC₅₀ & Target^[1]

PARP2

0.87 nM (Ki)

PARP1

1.2 nM (Ki)

Cellular Effect

Cell Line	Type	Value	Description	References
CAPAN-1	EC₅₀	5 nM Compound: (8S,9R)-47; BMN 673; Talazoparib	Cytotoxicity against BRCA2-deficient human Capan1 cells Cytotoxicity against BRCA2-deficient human Capan1 cells	[PMID: 26652717]
CAPAN-1	IC₅₀	1.8 nM Compound: 5; BMN-673	Antiproliferative activity against human Capan1 cells after 7 days by CCK8 or SRB assay Antiproliferative activity against human Capan1 cells after 7 days by CCK8 or SRB assay	[PMID: 28692916]
CAPAN-1	IC₅₀	686.09 nM Compound: TP	Antiproliferative activity against human Olaparib-resistant CAPAN-1 cells assessed as cell proliferation inhibition incubated for 7 days by SRB assay Antiproliferative activity against human Olaparib-resistant CAPAN-1 cells assessed as cell proliferation inhibition incubated for 7 days by SRB assay	[PMID: 37605459]
CAPAN-1	IC₅₀	7.77 nM Compound: TP	Antiproliferative activity against human CAPAN-1 cells assessed as cell proliferation inhibition incubated for 7 days by SRB assay Antiproliferative activity against human CAPAN-1 cells assessed as cell proliferation inhibition incubated for 7 days by SRB assay	[PMID: 37605459]
CAPAN-1	IC₅₀	906.45 nM Compound: TP	Antiproliferative activity against human Talazoparib-resistant CAPAN-1 cells assessed as cell proliferation inhibition incubated for 7 days by SRB assay Antiproliferative activity against human Talazoparib-resistant CAPAN-1 cells assessed as cell proliferation inhibition incubated for 7 days by SRB assay	[PMID: 37605459]
DLD-1	IC₅₀	0.002 μM Compound: 4	Antiproliferative activity against human DLD-1 deficient in BRCA-2 cells measured after 7 days Antiproliferative activity against human DLD-1 deficient in BRCA-2 cells measured after 7 days	[PMID: 34570508]
DLD-1	IC₅₀	0.003 μM Compound: Talazoparib	Cytotoxicity against human DLD-1 cells with BRCA2 knockout assessed as reduction in cell proliferation incubated for 5 days by sulforhodamine B analysis Cytotoxicity against human DLD-1 cells with BRCA2 knockout assessed as reduction in cell proliferation incubated for 5 days by sulforhodamine B analysis	[PMID: 37484567]
DLD-1	IC₅₀	0.004 μM Compound: Talazoparib	Cytotoxicity against human DLD1 cells expressing BRCA2 knockout assessed as reduction in cell proliferation incubated for 4 hrs under oxic condition followed by incubation for 5 days under oxic condition by sulforhodamine B staining based analysis Cytotoxicity against human DLD1 cells expressing BRCA2 knockout assessed as reduction in cell proliferation incubated for 4 hrs under oxic condition followed by incubation for 5 days under oxic condition by sulforhodamine B staining based analysis	[PMID: 37484567]
DLD-1	IC₅₀	0.006 μM Compound: Talazoparib	Cytotoxicity against human DLD1 cells expressing BRCA2 knockout assessed as reduction in cell proliferation incubated for 4 hrs under hypoxic condition followed by incubation for 5 days under oxic condition by sulforhodamine B staining based analysis Cytotoxicity against human DLD1 cells expressing BRCA2 knockout assessed as reduction in cell proliferation incubated for 4 hrs under hypoxic condition followed by incubation for 5 days under oxic condition by sulforhodamine B staining based analysis	[PMID: 37484567]
DLD-1	IC₅₀	0.122 μM Compound: Talazoparib	Cytotoxicity against human DLD-1 cells expressing BRCA2 assessed as reduction in cell proliferation incubated for 5 days by sulforhodamine B analysis Cytotoxicity against human DLD-1 cells expressing BRCA2 assessed as reduction in cell proliferation incubated for 5 days by sulforhodamine B analysis	[PMID: 37484567]
DLD-1	IC₅₀	0.65 μM Compound: Talazoparib	Cytotoxicity against human DLD1 cells assessed as reduction in cell proliferation incubated for 4 hrs under oxic condition followed by incubation for 5 days under oxic condition by sulforhodamine B staining based analysis Cytotoxicity against human DLD1 cells assessed as reduction in cell proliferation incubated for 4 hrs under oxic condition followed by incubation for 5 days under oxic condition by sulforhodamine B staining based analysis	[PMID: 37484567]
DLD-1	IC₅₀	0.86 μM Compound: Talazoparib	Cytotoxicity against human DLD1 cells assessed as reduction in cell proliferation incubated for 4 hrs under hypoxic condition followed by incubation for 5 days under oxic condition by sulforhodamine B staining based analysis Cytotoxicity against human DLD1 cells assessed as reduction in cell proliferation incubated for 4 hrs under hypoxic condition followed by incubation for 5 days under oxic condition by sulforhodamine B staining based analysis	[PMID: 37484567]
HCC1395	IC₅₀	0.46 nM Compound: Talazoparib	Anticancer activity against human HCC1395 cells assessed as cell growth inhibition Anticancer activity against human HCC1395 cells assessed as cell growth inhibition	[PMID: 38838546]
HCT-116	IC₅₀	0.009 μM Compound: Talazoparib	Cytotoxicity against human HCT-116 cells assessed as reduction in cell proliferation incubated for 4 hrs under oxic condition followed by incubation for 5 days under oxic condition by sulforhodamine B staining based analysis Cytotoxicity against human HCT-116 cells assessed as reduction in cell proliferation incubated for 4 hrs under oxic condition followed by incubation for 5 days under oxic condition by sulforhodamine B staining based analysis	[PMID: 37484567]
HCT-116	IC₅₀	0.013 μM Compound: Talazoparib	Cytotoxicity against human HCT-116 cells assessed as reduction in cell proliferation incubated for 4 hrs under hypoxic condition followed by incubation for 5 days under oxic condition by sulforhodamine B staining based analysis Cytotoxicity against human HCT-116 cells assessed as reduction in cell proliferation incubated for 4 hrs under hypoxic condition followed by incubation for 5 days under oxic condition by sulforhodamine B staining based analysis	[PMID: 37484567]
HCT-116	IC₅₀	0.018 μM Compound: Talazoparib	Cytotoxicity against human HCT-116 cells expressing N-terminally truncated POR/copGFP/puramycin resistance genes assessed as reduction in cell proliferation incubated for 4 hrs under hypoxic condition followed by incubation for 5 days under oxic condition Cytotoxicity against human HCT-116 cells expressing N-terminally truncated POR/copGFP/puramycin resistance genes assessed as reduction in cell proliferation incubated for 4 hrs under hypoxic condition followed by incubation for 5 days under oxic condition	[PMID: 37484567]
HCT-116	IC₅₀	0.019 μM Compound: Talazoparib	Cytotoxicity against human HCT-116 cells expressing N-terminally truncated POR/copGFP/puramycin resistance genes assessed as reduction in cell proliferation incubated for 4 hrs under oxic condition followed by incubation for 5 days under oxic condition by Cytotoxicity against human HCT-116 cells expressing N-terminally truncated POR/copGFP/puramycin resistance genes assessed as reduction in cell proliferation incubated for 4 hrs under oxic condition followed by incubation for 5 days under oxic condition by	[PMID: 37484567]
HEK293	IC₅₀	4.95 nM Compound: 2; BMN-673	Cytotoxicity against HEK293 cells assessed as inhibition of cell viability Cytotoxicity against HEK293 cells assessed as inhibition of cell viability	[PMID: 33120078]
LoVo	EC₅₀	2.5 nM Compound: 9, BMN 673	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 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	[PMID: 25761096]
LoVo	EC₅₀	2.51 nM Compound: (8S,9R)-47; BMN 673; Talazoparib	Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay	[PMID: 26652717]
LoVo	GI₅₀	4 nM Compound: (8S,9R)-47; BMN 673; Talazoparib	Potentiation of temozolomide-induced cytotoxicity in human LoVo cells assessed as temozolomide GI50 at 0.4 uM after 5 days by Celltiter-Glo assay Potentiation of temozolomide-induced cytotoxicity in human LoVo cells assessed as temozolomide GI50 at 0.4 uM after 5 days by Celltiter-Glo assay	[PMID: 26652717]
MDA-MB-157	IC₅₀	0.37 nM Compound: Talazoparib	Anticancer activity against human MDA-MB-157 cells assessed as cell growth inhibition Anticancer activity against human MDA-MB-157 cells assessed as cell growth inhibition	[PMID: 38838546]
MDA-MB-436	IC₅₀	0.012 nM Compound: 2; BMN-673	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 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	[PMID: 33120078]
MDA-MB-436	IC₅₀	0.38 nM Compound: 2; BMN-673	Cytotoxicity against human MDA-MB-436 cells assessed as inhibition of cell viability incubated for 4 days by CellTiterGlo luminescence assay Cytotoxicity against human MDA-MB-436 cells assessed as inhibition of cell viability incubated for 4 days by CellTiterGlo luminescence assay	[PMID: 33120078]
MDA-MB-436	IC₅₀	0.7 nM Compound: 5; BMN-673	Antiproliferative activity against human MDA-MB-436 cells after 7 days by CCK8 or SRB assay Antiproliferative activity against human MDA-MB-436 cells after 7 days by CCK8 or SRB assay	[PMID: 28692916]
MRC5	EC₅₀	0.31 μM Compound: (8S,9R)-47; BMN 673; Talazoparib	Cytotoxicity against human MRC5 cells Cytotoxicity against human MRC5 cells	[PMID: 26652717]
MX1	EC₅₀	0.3 nM Compound: (8S,9R)-47; BMN 673; Talazoparib	Cytotoxicity against BRCA1-deficient human MX1 cells Cytotoxicity against BRCA1-deficient human MX1 cells	[PMID: 26652717]
SUM149PT	EC₅₀	1.6 nM Compound: Talazoparib	Cytotoxicity against BRCA1-deficient human SUM149 cells measured after 6 days by microscopic analysis Cytotoxicity against BRCA1-deficient human SUM149 cells measured after 6 days by microscopic analysis	[PMID: 31042381]
SUM149PT	EC₅₀	23.2 nM Compound: Talazoparib	Cytotoxicity against BRCA1-proficient human SUM149 cells measured after 6 days by microscopic analysis Cytotoxicity against BRCA1-proficient human SUM149 cells measured after 6 days by microscopic analysis	[PMID: 31042381]
V79	IC₅₀	5011.4 nM Compound: 5; BMN-673	Cytotoxicity against BRCA2 expressing Chinese hamster V79 cells after 3 days by CCK8 or SRB assay Cytotoxicity against BRCA2 expressing Chinese hamster V79 cells after 3 days by CCK8 or SRB assay	[PMID: 28692916]

In Vitro

Talazoparib shows an EC₅₀ of 2.51 nM in cellular PARylation assay^[1].
Talazoparib shows EC₅₀s of 0.3 nM, 5 nM and 0.31 for MX-1 cells (BRCA1 mutant), Capan-1 cells (BRCA2 mutant) and MRC-5 cells (normal)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Talazoparib (0.33 mg/kg; i.g.; once daily; for 28 days) exhibits antitumor activity against BRCA1 mutant breast cancer model in mice^[1].
Talazoparib exhibits moderate oral bioavailability (rat 56%) and C_max (rat 7948 ng/mL) following oral administration (rat 10 mg/kg)^[1]. Talazoparib exhibits the terminal elimination half-life (rat 2.25 h) due to plasma clearance (2 mL/min/kg) following intravenous administration (rat 5 mg/kg)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Female athymic nu/nu mice (8-10 weeks old), with MX-1 xenograft-bearing mice^[1]
Dosage:	0.33 mg/kg
Administration:	Oral gavage, once daily, for 28 days
Result:	Significantly inhibited xenograft MX-1 tumor growth.

Animal Model:	Sprague-Dawley rats^[1]
Dosage:	5mg/kg for i.v.; 10 mg/kg for oral (Pharmacokinetic Analysis)
Administration:	Intravenous administration and oral administration
Result:	Oral bioavailability (56%), C_max (7948 ng/mL), T_1/2 (2.25 h).

Masse moléculaire

380.35

Formule

C₁₉H₁₄F₂N₆O

CAS No.

1207456-01-6

Appearance

Solid

Color

White to off-white

SMILES

O=C1NN=C2C3=C1C=C(F)C=C3N[C@H](C4=CC=C(F)C=C4)[C@H]2C5=NC=NN5C

Livraison

Room temperature in continental US; may vary elsewhere.

Stockage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	1 year
	-20°C	6 months

Solvant et solubilité

In Vitro:

DMSO : 25 mg/mL (65.73 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.6292 mL	13.1458 mL	26.2916 mL
5 mM	0.5258 mL	2.6292 mL	5.2583 mL
10 mM	0.2629 mL	1.3146 mL	2.6292 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (6.57 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 5% DMSO 95% (20% SBE-β-CD in Saline)
Solubility: 1.25 mg/mL (3.29 mM); Suspended solution; Need ultrasonic
Protocol 3

Add each solvent one by one: 2% DMSO 40% PEG300 5% Tween-80 53% Saline
Solubility: ≥ 0.5 mg/mL (1.31 mM); Clear solution
Protocol 4

Add each solvent one by one: 1% DMSO 99% Saline
Solubility: ≥ 0.25 mg/mL (0.66 mM); Clear solution

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMAc 6% Solutol HS-15 84% PBS
Solubility: 5 mg/mL (13.15 mM); Suspended solution; Need ultrasonic

Pureté et documentation

Purity: 99.89%

Fiche technique (282 KB) SDS (393 KB)

COA (254 KB) LCMS (125 KB) Elemental Analysis Report (112 KB)

Instruction de manipulation (2659 KB)

Références

[1]. Wang B, et al. Discovery and Characterization of (8S,9R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one (BMN 673, Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymerase-1/2 Inhibitor, as an Anticancer Agent. J Med Chem. 2016 Jan 14;59(1):335-57. [Content Brief]

[2]. Shen Y, et al. BMN 673, a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency.Clin Cancer Res. 2013 Sep 15;19(18):5003-15. [Content Brief]

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Référence HY-16106-5mg

Contactez votre distributeur local :

Marque : MedChemExpress

Contactez votre distributeur local :

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