Home DNA Damage/DNA Repair PARP inhibitor Talazoparib (BMN 673) For research use only.

Talazoparib (BMN 673)

Synonyms: LT-673

Talazoparib (BMN 673, LT-673) is a novel PARP inhibitor with IC50 of 0.57 nM for PARP1 in a cell-free assay. It is also a potent inhibitor of PARP-2, but does not inhibit PARG and is highly sensitive to PTEN mutation. Phase 3.

Talazoparib (BMN 673) Chemical Structure

Talazoparib (BMN 673) Chemical Structure

CAS No. 1207456-01-6

Purity & Quality Control

Talazoparib (BMN 673) Related Products

Signaling Pathway

PARP Signaling Pathways

PARP Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BR5FVB1-Akt Growth Inhibition Assay 0.1-100 nM 24/48/72 h inhibits cell proliferation dose dependently 26047697
BR5FVB1-Akt Apoptosis Assay 0.1-100 nM 72 h induces apoptosis 26047697
Capan-1 Growth Inhibition Assay IC50=16.0 ± 5.4 µM  25864590
MIA PaCa-2 Growth Inhibition Assay IC50=58.23 ± 8.1 µM  25864590
RD Growth Inhibition Assay IC50=8.7 nM 25263539
Rh41 Growth Inhibition Assay IC50=8.1 nM 25263539
Rh18 Growth Inhibition Assay IC50=4.9 nM 25263539
Rh30 Growth Inhibition Assay IC50=31.1 nM 25263539
BT-12 Growth Inhibition Assay IC50> 1,000 nM 25263539
CHLA-266 Growth Inhibition Assay IC50> 1,000 nM 25263539
TC-71 Growth Inhibition Assay IC50=3.7 nM 25263539
CHLA-9 Growth Inhibition Assay IC50=8.2 nM 25263539
CHLA-10 Growth Inhibition Assay IC50=67.8 nM 25263539
CHLA-258 Growth Inhibition Assay IC50=4.6 nM 25263539
SJ-GBM2 Growth Inhibition Assay IC50=16.2 nM 25263539
NB-1643 Growth Inhibition Assay IC50=18.4 nM 25263539
NB-EBc1 Growth Inhibition Assay IC50=25.8 nM 25263539
CHLA-90 Growth Inhibition Assay IC50> 1,000 nM 25263539
CHLA-136 Growth Inhibition Assay IC50=14.2 nM 25263539
NALM-6 Growth Inhibition Assay IC50=49 nM 25263539
COG-LL-317 Growth Inhibition Assay IC50=9.4 nM 25263539
RS4;11 Growth Inhibition Assay IC50=52.6 nM 25263539
MOLT-4 Growth Inhibition Assay IC50=16.6 nM 25263539
CCRF-CEM Growth Inhibition Assay IC50=697.3 nM 25263539
Kasumi-1 Growth Inhibition Assay IC50=786.2 nM 25263539
Karpas-299 Growth Inhibition Assay IC50=75.7 nM 25263539
Ramos-RA1 Growth Inhibition Assay IC50=68.3 nM 25263539
DT40 Growth Inhibition Assay IC50=4 nM 24356813
DU145 Growth Inhibition Assay IC50=11 nM 24356813
H209 Growth Inhibition Assay IC50=1.7 nM 24077350
H1048 Growth Inhibition Assay IC50=2.2 nM 24077350
H524 Growth Inhibition Assay IC50=3.1 nM 24077350
H1930 Growth Inhibition Assay IC50=4.1 nM 24077350
H69 Growth Inhibition Assay IC50=5.2 nM 24077350
H2081 Growth Inhibition Assay IC50=6.3 nM 24077350
H2107 Growth Inhibition Assay IC50=7.3 nM 24077350
H1092 Growth Inhibition Assay IC50=8.9 nM 24077350
DMS-79 Growth Inhibition Assay IC50=9.3 nM 24077350
H446 Growth Inhibition Assay IC50=13 nM 24077350
COR-L279 Growth Inhibition Assay IC50=15 nM 24077350
LoVo Function assay 30 mins EC50 = 0.0025 μM 25761096
MX1 Cytotoxicity assay EC50 = 0.0003 μM 26652717
LoVo Function assay 30 mins EC50 = 0.00251 μM 26652717
LoVo Cytotoxicity assay 0.4 uM 5 days GI50 = 0.004 μM 26652717
Capan1 Cytotoxicity assay EC50 = 0.005 μM 26652717
MRC5 Cytotoxicity assay EC50 = 0.31 μM 26652717
MX1 Function assay 1 mg/kg 2 ,8 and 24 hrs Decrease in PAR level in athymic nu/nu mouse xenografted with human MX1 cells at 1 mg/kg, po administered as single dose measured after 2 ,8 and 24 hrs by ELISA 26652717
MX1 Antitumor assay 0.33 mg/kg 28 days Antitumor activity against BRCA1 deficient human MX1 cells xenografted in athymic nu/nu mouse at 0.33 mg/kg, po qd administered for 28 days 26652717
MX1 Antitumor assay 0.165 mg/kg 28 days Antitumor activity against BRCA1 deficient human MX1 cells xenografted in athymic nu/nu mouse assessed as tumor growth inhibition at 0.165 mg/kg, po administered twice a day for 28 days 26652717
MX1 Function assay 0.33 mg/kg Potentiation of carboplatin-induced tumor growth inhibition of BRCA1 deficient human MX1 cells xenografted in athymic nu/nu mouse at 0.33 mg/kg po and animals were treated with carboplatin at 35 mg/kg, ip on day 1 26652717
MDA-MB-436 Antiproliferative assay 7 days IC50 = 0.0007 μM 28692916
Capan1 Antiproliferative assay 7 days IC50 = 0.0018 μM 28692916
VC8 Cytotoxicity assay 3 days IC50 = 0.0042 μM 28692916
V79 Cytotoxicity assay 3 days IC50 = 5.0114 μM 28692916
Capan1 Function assay 0.1 uM 4 hrs Inhibition of PARP1 in BRCA2 deficient human Capan1 cells assessed as increase in PARP1-DNA trapping at 0.1 uM after 4 hrs by Western blot analysis 28692916
MDA-MB-436 Function assay 1 uM 4 hrs Inhibition of PARP1 in BRCA1 deficient human MDA-MB-436 cells assessed as increase in PARP1-DNA trapping at 1 uM after 4 hrs by Western blot analysis 28692916
Click to View More Cell Line Experimental Data

Biological Activity

Description Talazoparib (BMN 673, LT-673) is a novel PARP inhibitor with IC50 of 0.57 nM for PARP1 in a cell-free assay. It is also a potent inhibitor of PARP-2, but does not inhibit PARG and is highly sensitive to PTEN mutation. Phase 3.
Features Most potent and selective PARPi reported thus far.
Targets
PARP1 [1]
(Cell-free assay)
0.57 nM
In vitro
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]

Off-target molecular screening did not identify significant non-specific activity for this class of PARP inhibitors. [2]
Cell Research Cell lines MDA-MB-436 cells
Concentrations 10 uM
Incubation Time 7 days
Method

Cells were treated with increasing doses of talazoparib for 7 days and subjected to cell viability assays to derive IC50 values.
Experimental Result Images Methods Biomarkers Images PMID
Western blot cleaved-PARP / cleaved-caspase3 / γ-H2AX pKAP1 / pChk2 / pChk1 PD-L1 p-ATM 29158830
Growth inhibition assay Cell viability 29158830
Immunofluorescence cleaved PARP / 53BP1 RAD51 28958991
In Vivo
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]
Animal Research Animal Models MX-1 model (BRCA-1 deficient)
Dosages 0.33 mg/kg/day, once daily
Administration Oral
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05425862 Suspended
Metastatic Castration Resistant Prostate Cancer (mCRPC)
Peter MacCallum Cancer Centre Australia
 October 21 2022 Phase 1
NCT05141708 Completed
Metastatic Breast Cancer|Breast Neoplasms
Pfizer
 December 17 2021 --
NCT05053854 Recruiting
Neuroendocrine Tumors
Peter MacCallum Cancer Centre Australia
 December 8 2021 Phase 1
NCT04991480 Active not recruiting
Advanced Cancer|Metastatic Cancer|Breast Cancer
Artios Pharma Ltd
 September 13 2021 Phase 1|Phase 2
NCT04987931 Completed
Breast Cancer
Pfizer
 August 20 2021 --

Chemical Information & Solubility

Molecular Weight 380.35 Formula

 

C19H14F2N6O
 
CAS No. 1207456-01-6 SDF --
Smiles CN1C(=NC=N1)C2C(NC3=CC(=CC4=C3C2=NNC4=O)F)C5=CC=C(C=C5)F
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 76 mg/mL ( (199.81 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
Batch:

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In vivo Formulation Calculator

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In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
Which solvent do you recommend to dilute the inhibitor for in vivo study in mice?

Answer:
BMN673 (S7048) can be dissolved in vehicle (10% DMAc, 6% Solutol, and 84% PBS) according to the paper: http://clincancerres.aacrjournals.org/content/19/18/5003.full. Quote from Method and Material section "Xenograft experiments: BMN 673 (various doses as indicated), or vehicle (10% DMAc, 6% Solutol, and 84% PBS) was administered by oral gavage"

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