| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg |
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| 250mg | |||
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| Targets |
AZD-9574 targets poly(ADP-ribose) polymerase 1 (PARP1). It is a selective inhibitor of PARP1 at the sites of SSBs. It shows >8000-fold selectivity for PARP1 compared to PARP2/3/5a/6. PARP1 is an enzyme involved in DNA repair, and its inhibition leads to the accumulation of DNA damage and cell death, particularly in cells with homologous recombination repair deficiency (HRD).
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| ln Vitro |
Regardless of the status of homologous recombination repair (HRR), AZD-9574 inhibits the enzymatic activity of PARP1 in all tested cell lines, with an IC50 ranging between 0.3-2 nM [1]. In homogenous cell lines, higher efficacy and effects were shown on HRR-deficient (HRD+) models (DLD1 BRCA2-/-, SKOV-3 BRCA2-/-, and SKOV-3 PALB2-/-). Compared to BRCA2wt cells, which had an IC50 >40 μM, BRCA2-/-DLD1 cells had an IC50 of 1.38 nM[1].
In vitro, AZD-9574 inhibits the enzymatic activity of PARP1 in all tested cell lines regardless of the status of homologous recombination repair (HRR). It acts by selectively inhibiting and trapping PARP1 at the sites of SSBs. The compound exhibits anti-cancer activities. It is a potent PARP1 inhibitor with high selectivity. |
| ln Vivo |
In an intracranial xenograft model of breast cancer brain metastases, AZD-9574 (3 mg/kg) displayed persistent growth suppression, greatly extending tumor-bearing tumor survival [1].
In vivo, AZD-9574 is a brain-penetrant PARP-1 selective inhibitor with activity in an orthotopic, intracranial xenograft model with aberrant DNA repair. It exhibits anti-cancer activities and can be used in studies about HRD+ breast cancer and advanced solid malignancies. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for AZD-9574 involves measuring its inhibition of PARP1 enzymatic activity. The compound's selectivity for PARP1 over PARP2/3/5a/6 is assessed by measuring inhibition of each enzyme's activity. The IC₅₀ values are determined by quantifying the reduction in PARP activity.
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| Cell Assay |
In vitro cell-based assays for AZD-9574 involve treating cancer cell lines with the compound and assessing cell viability, DNA damage, and PARP trapping. The compound's effects on cell proliferation and survival are evaluated in HRD+ and HRD- cell lines.
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| Animal Protocol |
In vivo animal studies for AZD-9574 involve orthotopic, intracranial xenograft models with aberrant DNA repair. Tumor-bearing mice are treated with AZD-9574, and tumor growth inhibition is monitored. The compound's brain penetration is assessed by measuring drug levels in the brain.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of AZD-9574 are not extensively detailed in the available literature. The compound is brain-penetrant. It is soluble in DMSO: 10 mg/mL (23.34 mM) or 86 mg/mL (200.72 mM) with fresh, anhydrous DMSO. It is insoluble in water and ethanol.
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| Toxicity/Toxicokinetics |
No specific toxicity data for AZD-9574 are available in the provided literature. The compound is for research use only and not for human therapeutic applications. Standard laboratory safety precautions should be followed when handling.
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| References | |
| Additional Infomation |
The PARP1 inhibitor AZD9574 is an orally bioavailable central nervous system (CNS) penetrator that inhibits ribonuclease-polymerase 1 (PARP1) and possesses potential antitumor activity. After oral administration, AZD9574 selectively binds to PARP1, thereby blocking the base excision repair (BER) pathway from repairing damaged DNA. This drug enhances the accumulation of DNA strand breaks, promotes genomic instability, and ultimately leads to apoptosis. AZD9574 may enhance the cytotoxicity of DNA-damaging drugs and reverse chemotherapy and radiotherapy resistance in tumor cells. PARP1 catalyzes post-translational ADP-ribosylation modification of nucleoproteins, which signal and recruit other proteins to repair damaged DNA, playing a crucial role in the repair of single-stranded DNA (ssDNA) breaks and double-stranded DNA (DSB). AZD9574 can cross the blood-brain barrier (BBB).
AZD-9574 is a novel PARP inhibitor combining PARP1 selectivity, trapping, and high CNS penetration. It is an anti-cancer agent for HRD+ breast cancer and advanced solid malignancies research. Its CAS number is 2756333-39-6. |
| Molecular Formula |
C21H22F2N6O2
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|---|---|
| Molecular Weight |
428.44
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| Exact Mass |
428.18
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| Elemental Analysis |
C, 58.87; H, 5.18; F, 8.87; N, 19.62; O, 7.47
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| CAS # |
2756333-39-6
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| PubChem CID |
162524593
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| Appearance |
White to yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
31
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| Complexity |
714
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(C(NC)=O)=NC(F)=C(N2CCN(CC3C=CC4=C(C=3F)NC(=O)C(C)=N4)CC2)C=C1
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| Synonyms |
AZD9574; AZD-9574; AZD 9574;
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~22.22 mg/mL (~51.86 mM)
DMSO : ~8.33 mg/mL (~19.44 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.22 mg/mL (5.18 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 22.2 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: ≥ 2.22 mg/mL (5.18 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 22.2 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. View More
Solubility in Formulation 3: ≥ 2.22 mg/mL (5.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3340 mL | 11.6702 mL | 23.3405 mL | |
| 5 mM | 0.4668 mL | 2.3340 mL | 4.6681 mL | |
| 10 mM | 0.2334 mL | 1.1670 mL | 2.3340 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.
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.
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