1. Cell Cycle/DNA Damage
    Epigenetics
  2. PARP

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

Cat. No.: HY-16106 Purity: 99.78%
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
NCT Number Sponsor Condition Start Date Phase
NCT01776437 Medivation, Inc. Human Volunteers February 2013 Phase 1
NCT01399840 Medivation, Inc. Acute Myeloid Leukemia|Myelodysplastic Syndrome|Chronic Lymphocytic Leukemia|Mantle Cell Lymphoma June 2011 Phase 1
NCT02127151 University College, London|Medivation, Inc. Endometrial Cancer Phase 2
NCT02316834 M.D. Anderson Cancer Center|BioMarin Pharmaceutical|National Cancer Institute (NCI) Fallopian Tube Cancer|Ovarian Cancer|Peritoneal Cancer June 2015 Early Phase 1
NCT02326844 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Ovarian Cancer March 2, 2015 Phase 2
NCT01989546 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Advanced Ovarian Cancer|Primary Peritoneal Cancer|Advanced Breast Cancer|Advanced Solid Tumors November 8, 2013 Phase 1|Phase 2
NCT02049593 Jonsson Comprehensive Cancer Center|National Cancer Institute (NCI) Metastatic Cancer|Unspecified Adult Solid Tumor June 12, 2014 Phase 1
NCT02358200 University of California, San Francisco|QuantumLeap Healthcare Collaborative Triple Negative Metastatic Breast Cancer|BRCA-mutated Solid Tumor February 23, 2015 Phase 1
NCT01776437 Medivation, Inc. Human Volunteers February 2013 Phase 1
NCT01399840 Medivation, Inc. Acute Myeloid Leukemia|Myelodysplastic Syndrome|Chronic Lymphocytic Leukemia|Mantle Cell Lymphoma June 2011 Phase 1
NCT02127151 University College, London|Medivation, Inc. Endometrial Cancer Phase 2
NCT02316834 M.D. Anderson Cancer Center|BioMarin Pharmaceutical|National Cancer Institute (NCI) Fallopian Tube Cancer|Ovarian Cancer|Peritoneal Cancer June 2015 Early Phase 1
NCT02326844 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Ovarian Cancer March 2, 2015 Phase 2
NCT01989546 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Advanced Ovarian Cancer|Primary Peritoneal Cancer|Advanced Breast Cancer|Advanced Solid Tumors November 8, 2013 Phase 1|Phase 2
NCT02049593 Jonsson Comprehensive Cancer Center|National Cancer Institute (NCI) Metastatic Cancer|Unspecified Adult Solid Tumor June 12, 2014 Phase 1
NCT02358200 University of California, San Francisco|QuantumLeap Healthcare Collaborative Triple Negative Metastatic Breast Cancer|BRCA-mutated Solid Tumor February 23, 2015 Phase 1
NCT02282345 M.D. Anderson Cancer Center|Medivation, Inc. Breast Cancer April 2015 Phase 2
NCT03070548 Medivation, Inc. Advanced Solid Tumors September 2016 Phase 1
NCT01286987 Medivation, Inc.|Pfizer Advanced or Recurrent Solid Tumors|Breast Neoplasms|Ovarian Cancer, Epithelial|Ewing Sarcoma|Small Cell Lung Carcinoma|Prostate Cancer|Pancreas Cancer December 2010 Phase 1
NCT03042910 Medivation, Inc. Solid Tumor October 2016 Phase 1
NCT02567396 National Cancer Institute (NCI) Estrogen Receptor Negative|Head and Neck Squamous Cell Carcinoma|HER2/Neu Negative|Hormone-Resistant Prostate Cancer|Metastatic Pancreatic Adenocarcinoma|Progesterone Receptor Negative|Solid Neoplasm|Stage III Mesothelioma|Stage IIIA Gastric Cancer|Stage IIIA Non-Small Cell Lung Cancer|Stage IIIA Ovarian Cancer|Stage IIIA Small Cell Lung Carcinoma|Stage IIIB Gastric Cancer|Stage IIIB Non-Small Cell Lung Cancer|Stage IIIB Ovarian Cancer|Stage IIIB Small Cell Lung Carcinoma|Stage IIIC Gastric Canc June 2016 Phase 1
NCT02997163 Medivation, Inc. Advanced Solid Tumors January 2017 Phase 1
NCT02997176 Medivation, Inc. Advanced Solid Tumors November 2016 Phase 1
NCT02286687 M.D. Anderson Cancer Center|BioMarin Pharmaceutical Advanced Cancers December 22, 2014 Phase 2
NCT02401347 Melinda Telli|National Cancer Institute (NCI)|Stanford University Advanced Breast Cancer|HER2/Neu Negative|Triple-Negative Breast Cancer August 2015 Phase 2
NCT03148795 Pfizer|Medivation, Inc. Prostate Cancer May 2017 Phase 2
NCT02034916 Medivation, Inc.|Myriad Genetic Laboratories, Inc. Breast Neoplasms|BRCA 1 Gene Mutation|BRCA 2 Gene Mutation January 2014 Phase 2
NCT02836028 Medivation, Inc.|Myriad Genetic Laboratories, Inc. Ovarian Cancer October 2016 Phase 2
NCT02878785 University of Maryland|Medivation, Inc. Acute Myeloid Leukemia August 2016 Phase 1|Phase 2
NCT02627430 National Cancer Institute (NCI) Adult Solid Neoplasm|Estrogen Receptor Negative|Fallopian Tube Serous Neoplasm|HER2/Neu Negative|Ovarian Serous Adenocarcinoma|Ovarian Serous Tumor|Primary Peritoneal Serous Adenocarcinoma|Progesterone Receptor Negative|Recurrent Breast Carcinoma|Recurrent Fallopian Tube Carcinoma|Recurrent Ovarian Carcinoma|Recurrent Primary Peritoneal Carcinoma|Triple-Negative Breast Carcinoma March 2016 Phase 1
NCT02392793 St. Jude Children's Research Hospital|BioMarin Pharmaceutical|Alliance Pharma|Pfizer Childhood Solid Tumors March 25, 2015 Phase 1
NCT02921919 Medivation, Inc. Cancer September 2016 Phase 2
NCT02317874 National Cancer Institute (NCI) Advanced Malignant Solid Neoplasm|BRCA Rearrangement|BRCA1 Gene Mutation|BRCA2 Gene Mutation|Deleterious BRCA1 Gene Mutation|Deleterious BRCA2 Gene Mutation|Metastatic Malignant Solid Neoplasm|Unresectable Solid Neoplasm July 24, 2015 Phase 1
NCT01945775 Medivation, Inc.|Medivation is now a wholly owned subdiary of Pfizer, Inc. Breast Neoplasms|BRCA 1 Gene Mutation|BRCA 2 Gene Mutation October 2013 Phase 3
NCT02537561 Washington University School of Medicine|BioMarin Pharmaceutical Solid Tumors|Carcinoma, Non-Small Cell Lung|Non-Small Cell Lung Cancer|Non-Small-Cell Lung Carcinoma|Nonsmall Cell Lung Cancer December 2015 Phase 1
NCT02116777 National Cancer Institute (NCI) Adult Solid Neoplasm|Childhood Solid Neoplasm|Recurrent Adult Acute Lymphoblastic Leukemia|Recurrent Childhood Acute Lymphoblastic Leukemia|Recurrent Childhood Central Nervous System Neoplasm|Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor|Recurrent Malignant Solid Neoplasm|Refractory Central Nervous System Neoplasm May 16, 2014 Phase 1|Phase 2
NCT03077607 Medivation, Inc. Advanced Solid Tumors January 2017 Phase 1
NCT01042379 QuantumLeap Healthcare Collaborative Breast Neoplasms|Breast Cancer|Breast Tumors March 2010 Phase 2
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References
Preparing Stock Solutions
Concentration Volume (DMSO) 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
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

Please store the product under the recommended conditions in the Certificate of Analysis.

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: 99.78%

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BMN-673
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