1. Cell Cycle/DNA Damage
    Epigenetics
  2. PARP

BMN-673 (Synonyms: Talazoparib; LT-673)

Cat. No.: HY-16106 Purity: 99.83%
Data Sheet SDS Handling Instructions

BMN-673 is a novel PARP1/2 inhibitor with IC50 of 0.57 nM for PARP1.

For research use only. We do not sell to patients.
BMN-673 Chemical Structure

BMN-673 Chemical Structure

CAS No. : 1207456-01-6

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $165 In-stock
5 mg $150 In-stock
10 mg $240 In-stock
50 mg $650 In-stock
100 mg $1100 In-stock
200 mg $1700 In-stock
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Other Forms of BMN-673:

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

BMN-673 is a novel PARP1/2 inhibitor with IC50 of 0.57 nM for PARP1.

IC50 & Target

IC50: 0.57 nM (PARP1)[1]
Ki: 1.2/0.87 nM (PARP1/2)[1]

In Vitro

BMN-673 demonstrates excellent potency, inhibiting PARP1 and PARP2 enzyme activity with Ki=1.2 and 0.87 nM, respectively[1]. BMN 673 exhibits selective antitumor cytotoxicity and elicits DNA repair biomarkers at much lower concentrations than earlier generation PARP1/2 inhibitors (such as Olaparib, Rucaparib, and Veliparib)[2].

In Vivo

BMN-673 (1 mg/kg, p.o.) is orally available, displaying favorable pharmacokinetic (PK) properties and remarkable antitumor efficacy in the BRCA1 mutant MX-1 breast cancer xenograft model following oral administration as a single-agent or in combination with chemotherapy agents such as temozolomide and cisplatin[1]. BMN 673 is readily orally bioavailable, with more than 40% absolute oral bioavailability in rats when dosed in carboxylmethyl cellulose. Oral administration of BMN 673 elicits remarkable antitumor activity, xenografted tumors that carry defects in DNA repair due to BRCA mutations or PTEN deficiency are profoundly sensitive to oral BMN 673 treatment at well-tolerated doses in mice[2].

Clinical Trial
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References
Preparing Stock Solutions
Concentration Volume 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
Please refer to the solubility information to select the appropriate solvent.
Kinase Assay
[1]

The ability of a test compound to inhibit PARP1 enzyme activity is assessed using PARP1 assay kit. IC50 values are calculated using GraphPad Prism5 software. For PARP inhibitor Ki determination, enzyme assays are conducted in 96-well FlashPlate with 0.5 U of PARP1 enzyme, 0.25× activated DNA, 0.2 μCi [3H]NAD, and 5 μM cold NAD in a final volume of 50 μL in reaction buffer containing 10% glycerol (v/v), 25 mM HEPES, 12.5 mM MgCl2, 50 mM KCl, 1 mM dithiothreitol (DTT), and 0.01% NP-40 (v/v), pH 7.6. Reactions are initiated by adding NAD to the PARP reaction mixture with or without inhibitors and incubated for 1 min at room temperature. Fifty microliters of ice-cold 20% trichloroacetic acid (TCA) is then added to each well to quench the reaction. The plate is sealed and shaken for a further 120 min at room temperature, followed by centrifugation. Radioactive signal bound to the FlashPlate is determined using TopCount. PARP1 Km is determined using the Michaelis-Menten equation from various substrate concentrations (1-100 μM NAD). Compound Ki is calculated from the enzyme inhibition curve according to the following formula: Ki=IC50/[1+(substrate)/Km]. Km for PARP2 enzyme and compound Ki are determined with the same assay protocol except that 30 ng of PARP2, 0.25× activated DNA, 0.2 μCi [3H]NAD, and 20 μM cold NAD are used in the reaction for 30 min at room temperature[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

BMN-673 is dissolved in DMSO and stored, and then diluted with appropriate medium before use[1].

In single-agent assays, Capan-1 cells (BRCA2-deficient), MX-1 (BRCA1-deficient) cells, or other cultured cells are seeded at densities that allow linear growth for 10-12 days in 96-well plates (typically 500-3000 cells/well). Cells are treated in their recommended growth media containing varying concentrations of PARP inhibitors (Veliparib, Rucaparib, Niraparib, Olaparib, and BMN-673) for 10-12 consecutive days (media are changed with fresh compounds every 5 days). IC50 values are calculated using GraphPad Prism5[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

BMN-673 is prepared in 10% DMAc, 6% Solutol, and 84% PBS (Mice)[1].

Mice[1]
MX-1 tumor xenografts are prepared. When tumors reach an average volume of approximately 150 mm3, Olaparib (100 mg/kg), BMN-673 (1 mg/kg), or vehicle is administered in a single po dose. Tumors are harvested at 2, 8, and 24 h after drug dosing and snap-frozen in liquid nitrogen. Tumor tissue is then homogenized in PBS on ice and extracted with lysis buffer (25 mM Tris, pH 8.0, 150 mM NaCl, 5 mM EDTA, 2 mM EGTA, 25 mM NaF, 2 mM Na3VO4, 1 mM Pefabloc, 1% Triton X-100, and protease inhibitor cocktail) containing 1% SDS. Levels of PAR in the tumor lysates are determined by ELISA using PARP in vivo PD assay II kit. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

380.35

Formula

C₁₉H₁₄F₂N₆O

CAS No.

1207456-01-6

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.83%

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