| 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 |
JAK1 and JAK2 (Janus kinases).
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| ln Vitro |
In cell‑free kinase assays, (1R)-AZD-1480 inhibits JAK1 and JAK2 with reported IC₅0 values in the low nanomolar range for the parent compound AZD-1480. The (1R) isomer retains the inhibitory activity against both JAK1 and JAK2. The molecular formula is C14H14ClFN₈ and the molecular weight is 348.77. The compound is soluble in DMSO at 100 mg/mL (286.72 mM).
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| ln Vivo |
This entry is not available. As a JAK1/2 inhibitor, (1R)-AZD-1480 is expected to block STAT3 and STAT5 phosphorylation, leading to reduced expression of anti‑apoptotic proteins (e.g., BCL‑XL, MCL‑1, survivin) and pro‑proliferative genes (e.g., MYC, cyclin D1). This results in growth arrest and apoptosis in JAK/STAT‑dependent cancer cells, including Hodgkin lymphoma and other hematologic malignancies.
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| Enzyme Assay |
General cell‑free protocol for JAK2 inhibition: Use a radiometric kinase assay or a time‑resolved fluorescence (TR‑FRET) assay. Recombinant JAK2 enzyme (catalytic domain) is incubated with a peptide substrate (e.g., biotinylated JAK2tide) in kinase buffer (25 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.01% Tween‑20). Add varying concentrations of (1R)-AZD-1480 (0.1 nM to 10 uM) and ATP (10‑100 uM, adjusted to the Km of JAK2). After 30‑60 minutes at room temperature, stop the reaction with EDTA. Detect phosphorylated substrate using an anti‑phosphotyrosine antibody (e.g., PY20) labeled with Eu (donor) and streptavidin‑XL665 (acceptor) in TR‑FRET format. Calculate IC₅0 from the inhibition curve. Perform similar assays for JAK1.
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| Cell Assay |
General cellular protocol for JAK1/2 inhibitors: Seed JAK/STAT‑dependent cancer cells (e.g., Hodgkin lymphoma cell lines L‑428, KM‑H2, or U266 multiple myeloma cells) in 6‑well plates. Treat cells with (1R)-AZD-1480 at concentrations of 0.01, 0.1, 0.5, 1, 2.5, 5, 10 uM for 24‑72 hours. Assess STAT phosphorylation: after treatment, stimulate cells with IL‑6 (20 ng/mL, 15 minutes) or other relevant cytokines, then lyse cells and perform Western blot with anti‑pSTAT3 (Tyr705), anti‑pSTAT5 (Tyr694), and anti‑total STAT3/STAT5. Assess cell viability using MTT or CellTiter‑Glo assay. Assess apoptosis by Annexin V/PI staining and flow cytometry, or by measuring cleaved PARP and cleaved caspase‑3 by Western blot. Assess proliferation by 3H‑thymidine incorporation or EdU staining.
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| Animal Protocol |
General animal protocol for JAK inhibitors: Establish subcutaneous xenografts of Hodgkin lymphoma cells (L‑428 or KM‑H2) in immunocompromised mice. When tumors reach ~150 mm3, randomize mice into treatment groups (n=8/group). Administer (1R)-AZD-1480 via oral gavage at doses of 10, 30, and 100 mg/kg daily for 2‑3 weeks. Measure tumor volume twice weekly. At study end, harvest tumors for Western blot analysis of pSTAT3, pSTAT5, and downstream targets (BCL‑XL, MCL‑1, MYC). Perform immunohistochemistry for Ki‑67 and cleaved caspase‑3. For combination studies, combine with other chemotherapeutic agents or targeted therapies. Monitor body weight and clinical signs for toxicity.
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| ADME/Pharmacokinetics |
General PK protocol for (1R)-AZD-1480: Administer (1R)-AZD-1480 to male Sprague‑Dawley rats via oral (PO, 10 mg/kg) and intravenous (IV, 2 mg/kg) routes. Formulate in an appropriate vehicle (e.g., 0.5% methylcellulose or 10% DMSO in saline). Collect blood samples at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours. Analyze plasma concentrations by LC‑MS/MS. Calculate PK parameters: Cmax, Tmax, AUC, t1/2, clearance (CL), volume of distribution (Vd), and oral bioavailability (F%). The parent compound AZD-1480 is orally bioavailable.
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| Toxicity/Toxicokinetics |
General toxicity protocol for (1R)-AZD-1480: Perform a 14‑day repeated dose oral toxicity study in Sprague‑Dawley rats. Administer (1R)-AZD-1480 at doses of 10, 30, and 100 mg/kg/day. Monitor body weight, food consumption, and clinical signs daily. At termination, collect blood for hematology (CBC, differential, platelets) and serum chemistry (ALT, AST, ALP, BUN, creatinine, total protein, albumin). Perform gross necropsy and collect major organs (liver, kidney, spleen, heart, lung, gastrointestinal tract, bone marrow) for histopathological examination. Assess potential myelosuppression (decreased white blood cell counts, anemia) which is a known on‑target effect of JAK inhibition.
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| References | |
| Additional Infomation |
(1R)-AZD-1480 is the (1R) chiral isomer of AZD-1480, a pyrimidine‑based small molecule JAK1/2 inhibitor. The parent compound AZD-1480 was developed by AstraZeneca and has been evaluated in clinical trials for various cancers. The JAK/STAT pathway is constitutively activated in many hematological malignancies and solid tumors, and inhibition of JAK1/2 leads to anti‑proliferative and pro‑apoptotic effects. The compound is used as a research tool to study JAK/STAT signaling and to evaluate the therapeutic potential of JAK inhibition in cancer models. The molecular weight is 348.77, and the compound is stored at 4degC protected from light.
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| Molecular Formula |
C14H14CLFN8
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|---|---|
| Molecular Weight |
348.77
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| CAS # |
935666-99-2
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8672 mL | 14.3361 mL | 28.6722 mL | |
| 5 mM | 0.5734 mL | 2.8672 mL | 5.7344 mL | |
| 10 mM | 0.2867 mL | 1.4336 mL | 2.8672 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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