Antibodies
BMN 673
- 貨號 Cat. No.
- S7048
- 規格 Size
- 10mgã€50mg
- 品牌 Brand
- Selleckchem
Description
BMN 673
Catalog No.S7048
BMN 673 is a novel PARP inhibitor with IC50 of 0.58 nM. It is also a potent inhibitor of PARP-2, but does not inhibit PARG and is highly sensitive to PTEN mutation. Phase 1.
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Biological Activity
| Description | BMN 673 is a novel PARP inhibitor with IC50 of 0.58 nM. It is also a potent inhibitor of PARP-2, but does not inhibit PARG and is highly sensitive to PTEN mutation. Phase 1. | |||||
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| Targets | PARP | |||||
| IC50 | 0.58 nM [1] | |||||
| In vitro | BMN-673 selectively binds to PARP and prevents PARP-mediated DNA repair of single strand DNA breaks via the base-excision repair pathway. This enhances the accumulation of DNA strand breaks, promotes genomic instability and eventually leads to apoptosis. BMN 673 selectively kills cancer cells with BRCA-1 or BRCA-2 mutations. BMN 673 demonstrates single-agent cytotoxicityin BRCA-1 mutant (MX-1, IC50 = 0.3 nM) and BRCA-2 mutant cells (Capan-1, IC50 = 5 nM). In contrast, in MRC-5 normal human fibroblastand other tumor cell lines with wild-type BRCA-1 and BRCA-2 genes, IC50 of BMN 673 ranges between 90 nM and 1.9 μM. [1] In cultured human cancer cells, BMN 673 also significantly enhances the cytotoxic efficacy of both Temozolomide and SN-38. Off-target molecular screening did not identify significant non-specific activity for this class of PARP inhibitors. [2] | |||||
| In vivo | In rat pharmacokinetic studies, BMN 673 displays >50% oralbioavailability and pharmacokinetic properties that enable singledaily dosing. In MX-1 xenograft tumor model studies, daily oral dosingof BMN 673 significantly enhances the antitumor effects ofcytotoxic therapies in a dose-dependent manner. [2] | |||||
| Features | Most potent and selective PARPi reported thus far. | |||||
Protocol(Only for Reference)
Animal Study: [2]
| Animal Models | MX-1 model (BRCA-1 deficient) |
|---|---|
| Dosages | 0.33 mg/kg/day, once daily |
| Administration | Oral |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01286987 | Recruiting | Advanced or Recurrent Solid Tumors|Breast Neoplasms|Ovarian Cancer, Epithelial|Ewing Sarcoma|Small Cell Lung Carcinoma|Prostate Cancer|Pancreas Cancer | BioMarin Pharmaceutical | 2010-12 | Phase 1 |
| NCT01399840 | Active, not recruiting | Acute Myeloid Leukemia|Myelodysplastic Syndrome|Chronic Lymphocytic Leukemia|Mantle Cell Lymphoma | BioMarin Pharmaceutical | 2011-06 | Phase 1 |
| NCT01776437 | Active, not recruiting | Human Volunteers | BioMarin Pharmaceutical | 2013-02 | Phase 1 |
Chemical Information
| Molecular Weight (MW) | 380.35 |
|---|---|
| Formula |
C19H14F2N6O |
| CAS No. | 1207456-01-6 |
| Storage | 3 years -20℃Powder |
|---|---|
| 6 months-80℃in DMSO | |
| Syonnyms | LT-673 |
| Solubility (25°C) * | In vitro | DMSO | 76 mg/mL (199 mM) |
|---|---|---|---|
| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | 3H-Pyrido[4,3,2-de]phthalazin-3-one, 5-fluoro-8-(4-fluorophenyl)-2,7,8,9-tetrahydro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-, (8S,9R)- |
|---|
Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
|---|---|---|---|---|
| Mass(mg) | 0.38035 | 3.8035 | 7.607 | 11.4105 |
