AZD-9574 is a potent, BBB (blood-brain barrier) permeable/penetrable PARP1 inhibitor that displays >8000-fold selectivity for PARP1 compared to PARP2/3/5a/6. AZD-9574 selectively inhibits PARP1 at the SSB site. AZD-9574 is an anticancer compound studied in HRD+ breast cancer and advanced solid malignancies.

Physicochemical Properties

Molecular Formula	C21H22F2N6O2
Molecular Weight	428.44
Exact Mass	428.18
Elemental Analysis	C, 58.87; H, 5.18; F, 8.87; N, 19.62; O, 7.47
CAS #	2756333-39-6
PubChem CID	162524593
Appearance	White to yellow solid powder
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	4
Heavy Atom Count	31
Complexity	714
Defined Atom Stereocenter Count	0
SMILES	C1(C(NC)=O)=NC(F)=C(N2CCN(CC3C=CC4=C(C=3F)NC(=O)C(C)=N4)CC2)C=C1
Synonyms	AZD9574; AZD-9574; AZD 9574;
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)

Biological Activity

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].
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].
References	[1]. Hybrid meeting divulges structures of drug candidates. [2]. Abstract 2609: AZD9574 is a novel, brain penetrant PARP-1 selective inhibitor with activity in an orthotopic, intracranial xenograft model with aberrant DNA repair. Cancer Res (2022) 82 (12_Supplement): 2609.
Additional Infomation	PARP1 Inhibitor AZD9574 is an orally bioavailable central nervous system (CNS) penetrant and inhibitor of nuclear enzyme poly(ADP-ribose) polymerase (PARP) 1, with potential antineoplastic activity. Upon oral administration, PARP1 inhibitor AZD9574 selectively binds to PARP1, thereby preventing repair of damaged DNA via the base excision repair (BER) pathway. This agent enhances the accumulation of DNA strand breaks and promotes genomic instability eventually leading to apoptosis. AZD9574 may enhance the cytotoxicity of DNA-damaging agents and reverse tumor cell chemo- and radioresistance. PARP1 catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA and plays a key role in the repair of single strand DNA (ssDNA) breaks and double-strand break (DSBs). AZD9574 is able to penetrate the blood-brain barrier (BBB).

Solubility Data

Solubility (In Vitro)

DMSO : ~22.22 mg/mL (~51.86 mM) DMSO : ~8.33 mg/mL (~19.44 mM)

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. 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. 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 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	2.3340 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.