| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
AZ10397767 targets the CXCR2 receptor, a chemokine receptor involved in neutrophil recruitment and inflammation. By inhibiting CXCR2, it reduces the numbers of infiltrating neutrophils into tumors. This inhibits tumor growth and enhances the effects of chemotherapy.
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| ln Vitro |
AZ10397767 (20 nM; 48 hours) suppresses cell proliferation induced by IL-8 (3 nM) and lowers cell counts below baseline [2]. The cytotoxicity and induction of oxaliplatin are both enhanced by AZ10397767 (20 nM; 72). In PC3 or DU145 cells, AZ10397767 by itself cannot be induced [3]. AZ10397767 (20 nM; 24 hours) reduces PC3 and DU145 cell toxicity and relieves NF-κB activity induced by oxaliplatin.
In vitro, AZ10397767 inhibits CXCR2 with an IC50 of 1 nM. It reduces NF-κB transcriptional activity induced by oxaliplatin. It potentiates oxaliplatin-induced apoptosis in androgen-independent prostate cancer (AIPC) cells. |
| ln Vivo |
AZ10397767 (100 mg/kg; gavage; twice daily; for 22 days) in A549 xenograft tumors shows decreased tumor growth and neutrophil perfusion [4].
In vivo, AZ10397767 is orally active. It significantly reduces neutrophil recruitment to tumors, which inhibits tumor growth. It enhances the antitumor efficacy of oxaliplatin in vivo. It shows potential for cancer and inflammation research. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays are performed using CXCR2 receptor binding studies. The compound is incubated with CXCR2-expressing cell membranes and radiolabeled ligands at concentrations ranging from 0.001-100 µM. Binding affinity is measured and IC50 values are calculated from displacement curves.
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| Cell Assay |
cell proliferation assay [2]
Cell Types: LNCaP cells and 22Rv1 cells Tested Concentrations: 20nM Incubation Duration: Cytokine ( CXCL8 and CXCL1) and increased levels of mRNA regulation of antioxidant genes (Bcl-2 and Svivin) [3]. Results at 48 hrs (hours): Abrogation of IL-8-induced (3 nM) increase in proliferation and reduction of cell numbers below basal levels. Apoptosis analysis[3] Cell Types: PC3 or DU145 Cell Tested Concentrations: 20 nM Incubation Duration: 72 hrs (hours) Experimental Results: Co-administration with 0.1 or 1 μM oxaliplatin resulted in sub-G0/G1 cell populations in either cell line increasing. Enhances oxaliplatin-induced AIPC cell apoptosis. RT-PCR[3] Cell Types: PC3 or DU145 Cell Tested Concentrations: 20 nM Incubation Duration: 24 hrs (hours) Experimental Results: Attenuation of oxaliplatin (1 μM)-induced NF-κB transcriptional activity and increase in each CXC mRNA transcript level - Chemokines (CXCL8 and CXCL1) and anti-apoptotic genes (Bcl-2 and survivin) in PC3 and DU145 cells. In vitro cellular assays are performed using cancer cell lines (e.g., AIPC cells). Cells are treated with AZ10397767 at concentrations ranging from 0.001-10 µM. NF-κB activity is measured by reporter assays. Apoptosis is assessed by caspase activation or Annexin V staining. |
| Animal Protocol |
Animal/Disease Models: A549 cell SCID (severe combined immunodeficient) mouse[4]
Doses: 100 mg/kg Route of Administration: oral administration; CL in mice is 4 ml/min/kg[1]. twice (two times) daily; 22-day Experimental Results: Tumors 36% smaller than control tumors. Significant (p < 0.01) reduction in the number of tumor-infiltrating neutrophils compared with mice receiving vehicle control. In vivo animal experiments are conducted using xenograft mouse models. AZ10397767 is administered orally at doses typically ranging from 1-50 mg/kg. Tumor volume is measured. Neutrophil infiltration into tumors is assessed by immunohistochemistry. Chemotherapy efficacy is evaluated in combination with oxaliplatin. |
| References |
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| Molecular Formula |
C15N4O2FS2CLH14
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|---|---|
| Molecular Weight |
400.8787
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| Exact Mass |
400.023
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| CAS # |
333742-63-5
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| PubChem CID |
11858154
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.6±0.1 g/cm3
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| Index of Refraction |
1.708
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| LogP |
5.03
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
25
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| Complexity |
481
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1C(F)=C(CSC2N=C(N[C@H](C)CO)C3SC(=O)NC=3N=2)C=CC=1
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| InChi Key |
KHTUORKUWBDRBX-SSDOTTSWSA-N
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| InChi Code |
InChI=1S/C15H14ClFN4O2S2/c1-7(5-22)18-12-11-13(21-15(23)25-11)20-14(19-12)24-6-8-3-2-4-9(16)10(8)17/h2-4,7,22H,5-6H2,1H3,(H2,18,19,20,21,23)/t7-/m1/s1
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| Chemical Name |
5-[(3-chloro-2-fluorophenyl)methylsulfanyl]-7-[[(2R)-1-hydroxypropan-2-yl]amino]-3H-[1,3]thiazolo[4,5-d]pyrimidin-2-one
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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) |
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 | 2.4945 mL | 12.4726 mL | 24.9451 mL | |
| 5 mM | 0.4989 mL | 2.4945 mL | 4.9890 mL | |
| 10 mM | 0.2495 mL | 1.2473 mL | 2.4945 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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