| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
CDK2[1]
CDK2 (cyclin‑dependent kinase 2). AZD8421 has an IC₅0 of 9 nM for CDK2 and shows >300‑fold selectivity over CDK9 and significant selectivity over CDK1, CDK4, and CDK6. It has no significant kinase inhibition outside the CDK family. |
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| ln Vitro |
In cell‑free enzymatic assays, AZD8421 inhibits CDK2 with an IC₅0 of 9 nM. It shows robust cellular efficacy by inhibiting retinoblastoma protein (pRB) phosphorylation, inducing G1/S cell cycle arrest and cellular senescence. AZD8421 potently inhibits the proliferation of breast and ovarian cancer cells, including those with acquired resistance to CDK4/6 inhibitors.
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| ln Vivo |
In vivo, AZD8421 demonstrates promising antitumor activity in an ovarian cancer patient‑derived xenograft (PDX) model with cyclin E1 overexpression, as well as in breast cancer models. It shows good single‑agent efficacy and synergistic activity when combined with CDK4/6 inhibitors (e.g., palbociclib) and other targeted therapies. The compound has favorable pharmacokinetic properties.
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| Enzyme Assay |
A general cell‑free protocol for CDK2 inhibition: A TR‑FRET kinase activity assay is used. Recombinant active human CDK2/cyclin A2 complex (5 nM) is incubated with a biotinylated retinoblastoma protein‑derived peptide substrate (0.5 uM) in kinase buffer (50 mM HEPES, pH 7.5, 10 mM MgCl2, 2 mM DTT) containing 10 uM ATP. Varying concentrations of AZD8421 (0.01 nM to 10 uM) are added. After 60 minutes at 25degC, the reaction is terminated with EDTA. An anti‑phospho‑pRB (Thr821) antibody labeled with a donor fluorophore (Eu) and streptavidin‑XL665 are added. The TR‑FRET signal is measured, and the IC₅0 is calculated.
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| Cell Assay |
A general cellular protocol for AZD8421: ER+ HER2‑ breast cancer cells (e.g., MCF‑7, T47D) or ovarian cancer cells (e.g., OV90, OVCAR3) are seeded in 96‑well plates. Cells are treated with serial dilutions of AZD8421 (0.1 nM to 10 uM) for 72‑120 hours. Cell viability is measured using CellTiter‑Glo assay. For mechanism studies, cells are treated for 24‑48 hours, lysed, and subjected to Western blot with anti‑phospho‑pRB (Ser780, Ser807/811), total pRB, and GAPDH antibodies. Senescence is assessed by beta‑galactosidase staining.
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| Animal Protocol |
A general animal protocol for AZD8421: Nude mice bearing CDK2‑dependent xenografts (e.g., OV0857F ovarian cancer PDX or MCF‑7 breast cancer xenografts) are randomized (n=8‑10/group). AZD8421 is formulated in a vehicle (e.g., 0.5% methylcellulose or 10% DMSO, 40% PEG300, 5% Tween‑80, 45% saline) and administered via oral gavage at doses of 100 and 150 mg/kg twice daily (BID) for 21‑28 days. Tumor volume is measured twice weekly. For combination studies, AZD8421 is combined with palbociclib (CDK4/6 inhibitor) or fulvestrant. At study end, tumors are harvested for pRB phosphorylation analysis, IHC (Ki‑67), and TUNEL staining.
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| ADME/Pharmacokinetics |
General PK protocol for AZD8421: Male Sprague‑Dawley rats are administered AZD8421 via oral gavage (PO, 10 mg/kg) and intravenous (IV, 2 mg/kg). Blood samples are collected at 0.083, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours post‑dose. Plasma concentrations are quantified by LC‑MS/MS. AZD8421 has favorable PK properties, including moderate oral bioavailability, a half‑life suitable for BID dosing, and low predicted human clearance.
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| Toxicity/Toxicokinetics |
General toxicity protocol for AZD8421: A 14‑day repeat‑dose oral toxicity study is performed in Sprague‑Dawley rats. AZD8421 is administered via oral gavage at doses of 30, 100, and 300 mg/kg/day for 14 days. Parameters include clinical signs, body weight, food consumption, hematology (complete blood count, differential), serum chemistry (ALT, AST, BUN, creatinine, total protein, albumin), and histopathology of the bone marrow, gastrointestinal tract, liver, and kidneys. Special attention is paid to the testes for potential testicular toxicity (a known class effect of CDK2 inhibitors in some preclinical models).
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| References | |
| Additional Infomation |
AZD8421 is currently being evaluated in the CYCAD‑1 Phase I/IIa first‑in‑human clinical trial (NCT06188520) for ER+ HER2‑ advanced breast cancer and metastatic high‑grade serous ovarian cancer. The compound was developed by AstraZeneca. The results of the Phase I trial are expected to determine the recommended Phase II dose (RP2D) and assess preliminary clinical activity in patients with CDK4/6 inhibitor‑resistant breast cancer and other CDK2‑dependent tumors.
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| Molecular Formula |
C18H32N8O3S
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|---|---|
| Molecular Weight |
440.56
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| Appearance |
Solid powder
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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 : 100 mg/mL (226.98 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.67 mM)(Saturation unknown) in 10% DMSO 40% PEG300 5% Tween-80 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, add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix well; then add 50 μL Tween-80 to the above system and mix well; then add 450 μL saline to make up 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: ≥ 2.5 mg/mL (5.67 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, add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD in saline and mix well. *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: ≥ 2.5 mg/mL (5.67 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, add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2698 mL | 11.3492 mL | 22.6984 mL | |
| 5 mM | 0.4540 mL | 2.2698 mL | 4.5397 mL | |
| 10 mM | 0.2270 mL | 1.1349 mL | 2.2698 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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