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Talazoparib (BMN 673)

Name: Talazoparib (BMN 673)
Brand: Selleck Chemicals
SKU: S7048
Rating: 5 (217 reviews)

Synonyms: LT-673

Catalog No.S7048 Purity: 99.84%

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

CAS: 1207456-01-6

Selleck's Talazoparib (BMN 673) has been cited by 217 publications

Purity & Quality Control

Batch: Purity: 99.84%

99.84

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Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	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

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] 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]
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
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-01-11)
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	--

References

Chemical lnformation & 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)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

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

Water : Insoluble

Ethanol : Insoluble

Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.

In vivo Formulation Calculator

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Molarity Calculator

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Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Working concentration: mg/ml;

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.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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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"

PARP Signaling Pathway Map

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C8=C7/X	C8:	LOG(C8):