Name: BMN-673 (Talazoparib)
Brand: Selleck Chemicals
SKU: S7048
Rating: 5 (272 reviews)

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Quality Control

Batch: Purity: 99.88%

99.88

Related Targets	HDAC ATM/ATR DNA-PK WRN DNA/RNA Synthesis Topoisomerase PPAR Sirtuin Casein Kinase eIF
Other PARP Inhibitors	XAV-939 AZD5305 (Saruparib) Veliparib (ABT-888) PJ34 HCl AG-14361 Iniparib (BSI-201) G007-LK Pamiparib UPF 1069 A-966492

Cell Culture, Treatment & Working Concentration

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

Chemical Information, Storage & Stability

Molecular Weight	380.35	Formula	C₁₉H₁₄F₂N₆O	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1207456-01-6	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	LT-673			Smiles	CN1C(=NC=N1)C2C(NC3=CC(=CC4=C3C2=NNC4=O)F)C5=CC=C(C=C5)F

Solubility

In vitro
Batch:

DMSO : 19 mg/mL (49.95 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.625mg/ml (1.64mM)	Taking the 1 mL working solution as an example, add 50 μL of 12.5 mg/mL clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG 300 2 5%Tween80 3 50% ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	2.500mg/ml (6.57mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/mL clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify; add 50 μL Tween-80 to the above system, mix evenly to clarify; Then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

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

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Features	Most potent and selective PARPi reported thus far.
Targets/IC₅₀/Ki	PARP1 (Cell-free assay) 0.57 nM
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. Off-target molecular screening did not identify significant non-specific activity for this class of PARP inhibitors.
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.
References	[1] http://www.selleckchem.com/products/bmn-673.html [2] http://cancerres.aacrjournals.org/cgi/content/meeting_abstract/70/8_MeetingAbstracts/3514 [3] https://pubmed.ncbi.nlm.nih.gov/31015319/

Applications

Methods	Biomarkers	PMID
Western blot	pKAP1 / pChk2 / pChk1 cleaved-PARP / cleaved-caspase3 / γ-H2AX p-ATM PD-L1	28947502
Growth inhibition assay	Cell viability	29158830
Immunofluorescence	cleaved PARP / 53BP1 RAD51	28958991

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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	--

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Frequently Asked Questions

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

Answer:
According to the paper: http://clincancerres.aacrjournals.org/content/19/18/5003.full, it can be dissolved in vehicle (10% DMAc, 6% Solutol, and 84% PBS). 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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C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

BMN-673 (Talazoparib) PARP inhibitor

Chemical Structure

Molecular Weight: 380.35