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AZ9482

Cat No.:V12016 Purity: ≥98%
AZ9482 is a triple inhibitor of PARP1/2/6, with IC50s of 1 nM, 1 nM and 640 nM for PARP1/2/6 respectively.
AZ9482
AZ9482 Chemical Structure CAS No.: 1825345-33-2
Product category: New1
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
1mg
5mg
10mg
Other Sizes
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Product Description
AZ9482 is a triple inhibitor of PARP1/2/6, with IC50s of 1 nM, 1 nM and 640 nM for PARP1/2/6 respectively.
Biological Activity I Assay Protocols (From Reference)
ln Vitro
In MDA-MB-468 cells, AZ9482 has an EC50 of 24 nM[1]. Treatment with AZ0108 causes CHK1 hyperphosphorylation and inhibits MARylation, which results in MPS formation and dysregulation of the cell cycle [1].
ln Vivo
Additionally, AZ0108 shows in vivo toxicity, the molecular cause of which is still unknown, which restricts AZ0108's pharmacological assessment [1].
Cell Assay
Cell viability assay [1]
Cell Types: MDA-MB-468 cells.
Tested Concentrations: 0-10μM.
Incubation Duration: 3 days.
Experimental Results: EC50 is 24 nM.
References

[1]. Structure-Guided Design and In-Cell Target Profiling of a Cell-Active Target Engagement Probe for PARP Inhibitors. ACS Chem Biol. 2020 Feb 21;15(2):325-333.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C26H22N6O2
Molecular Weight
450.49
Exact Mass
450.18
CAS #
1825345-33-2
PubChem CID
92045137
Appearance
White to yellow solid powder
LogP
2.6
Hydrogen Bond Donor Count
1
Hydrogen Bond Acceptor Count
6
Rotatable Bond Count
4
Heavy Atom Count
34
Complexity
842
Defined Atom Stereocenter Count
0
SMILES
C1=CC=NC(=C1C#N)N1CCN(CC1)C(=O)C1=CC=CC(CC2C3=C(C(NN=2)=O)C=CC=C3)=C1
InChi Key
ZDDPBFWHZOJFHF-UHFFFAOYSA-N
InChi Code
InChI=1S/C26H22N6O2/c27-17-20-7-4-10-28-24(20)31-11-13-32(14-12-31)26(34)19-6-3-5-18(15-19)16-23-21-8-1-2-9-22(21)25(33)30-29-23/h1-10,15H,11-14,16H2,(H,30,33)
Chemical Name
2-[4-[3-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]piperazin-1-yl]pyridine-3-carbonitrile
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO : ~125 mg/mL (~277.48 mM)
Solubility (In Vivo)
Solubility in Formulation 1: 2.08 mg/mL (4.62 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: 2.08 mg/mL (4.62 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.2198 mL 11.0990 mL 22.1981 mL
5 mM 0.4440 mL 2.2198 mL 4.4396 mL
10 mM 0.2220 mL 1.1099 mL 2.2198 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Biological Data
  • A photoaffinity-based probe (AfBP) PARPYnD was designed and synthesized for target profiling of AZ9482 and AZ0108. (A) Top: structures of clinical PARP1/2 inhibitor olaparib and MPS-inducing agents AZ0108 and AZ9482, the latter of which was diversified into the AfBP used in this study. Bottom: table showing the biochemical and biophysical parameters associated with olaparib, AZ9482, AZ0108, and PARPYnD.11,12 Table footnote a: data generated in this work, experiments performed in triplicate (±SEM); graphical analysis can be seen in Figure 2, and Supporting Information Figures S1 and S2 for multipolar spindle (MPS) induction data, PARP binding data, and cytotoxicity data (MDA-MB-468 cells), respectively. Table footnote b: cytotoxicity value represents a GI50 value previously generated in MDA-MB-468 cells.12 (B) Schematic of the photoaffinity labeling (PAL) workflow used for target profiling. The gray ball represents the recognition element of the probe that is designed based on the parent compound.[1].Structure-Guided Design and In-Cell Target Profiling of a Cell-Active Target Engagement Probe for PARP Inhibitors. ACS Chem Biol. 2020 Feb 21;15(2):325-333.
  • Validation of PARPYnD as a suitable probe for parent molecule profiling. (A) Crystal structure of parent molecule AZ9482 bound in the NAD+-binding pocket of PARP5a (PDB ID: 5ECE), with key interactions highlighted in orange. The red star highlights the solvent exposed position at which modification is expected to minimally perturb the binding of a probe into this pocket of the PARP enzymes. (B) Quantification of the percentage of mitotic cells with MPS phenotype (>2 spindle poles per cell) after treatment with AZ9482 (N = 2) and PARPYnD (N = 2), both at 41 nM, versus DMSO (N = 4); double asterisk (**) represents raw P value <0.001 in unpaired Student’s t test; raw data found in the Supporting Information, Extended Data S1. (C) PARP6 activity assay: recombinant GST-tagged PARP6 was incubated with biotinylated NAD+ and varying concentrations of PARPYnD. GST-PARP6 auto-MARylation was measured by immunoblotting against NeutrAvidin-HRP; decreased signal with increasing PARPYnD concentration indicated catalytic inhibition of PARP6. [1].Structure-Guided Design and In-Cell Target Profiling of a Cell-Active Target Engagement Probe for PARP Inhibitors. ACS Chem Biol. 2020 Feb 21;15(2):325-333.
  • Target engagement profiles of PARPYnD, AZ9482, AZ0108, and olaparib. (A–D) Proteomics analysis of live cells labeled with PARPYnD and ligated to AzRB (Figure S3B) with/without cotreatment with parent competitor molecules. Tagged proteins were enriched on NeutrAvidin agarose, digested into peptides, and tandem mass tag (TMT) labeled for identification and quantification by LC-MS/MS. Volcano plots demonstrate enrichment (x axis) of one sample versus another and the associated significance (y axis), determined by pairwise Student’s t test (cut off: A, S0 = 0.1, false discovery rate (FDR) = 5%; B–D, S0 = 0.1, FDR = 15%). Red diamonds = PARP family, blue dots = other significantly enriched/depleted hits, green squares = known background photocrosslinking binders,26 gray dots = nonsignificant proteins. Significant hits are annotated with their gene names only when they are appear significantly enriched/depleted across more than one pairwise comparison, with the exception of the known background binders.[1].Structure-Guided Design and In-Cell Target Profiling of a Cell-Active Target Engagement Probe for PARP Inhibitors. ACS Chem Biol. 2020 Feb 21;15(2):325-333.
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