AZ10397767
AZ10397767 is an orally active, selective CXCR2 receptor antagonist with an IC50 of 1 nM. AZ10397767 attenuates the Oxaliplatin (HY-17371)-induced NF-κB transcriptional activity and potentiates Oxaliplatin-induced apoptosis in androgen-independent prostate cancer (AIPC) cells. AZ10397767 significantly inhibits neutrophil recruitment into tumors which then adversely affects tumor growth in vitro and in vivo.
For research use only. We do not sell to patients.
- CAS No.: 333742-63-5
- Formula: C15H14ClFN4O2S2
- Molecular Weight:400.88
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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CXCR2 1 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
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| HEK293 | IC50 |
1 nM
Compound: 30a
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Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay
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[PMID: 18240390] |
AZ10397767 (20 nM; 48 h) abrogates the IL-8-induced (3 nM) increase in proliferation, reducing cell number to below basal levels[2].
AZ10397767 (20 nM; 72 h) increases Oxaliplatin (HY-17371) cytotoxicity, and potentiates Oxaliplatin-induced apoptosis in AIPC cells. AZ10397767 by itself fails to induce apoptosis in either PC3 or DU145 cells[3].
AZ10397767 (20 nM; 24 h) attenuates the Oxaliplatin-induced NF-κB transcriptional activity and the increases in mRNA transcript levels for each of the CXC-chemokines (CXCL8 and CXCL1) and antiapoptotic genes (Bcl-2 and survivin) in the PC3 and DU145 cells[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:LNCaP cells and 22Rv1 cells
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Concentration:20 nM
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Incubation Time:48 h
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Result:Abrogated the IL-8-induced (3 nM) increase in proliferation, reducing cell number to below basal levels.
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Cell Line:PC3 or DU145 cells
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Concentration:20 nM
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Incubation Time:72 h
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Result:Coadministration with 0.1 or 1 μM Oxaliplatin resulted in a marked increase in the sub-G0/G1 cell population in either cell line.
Potentiates Oxaliplatin-induced apoptosis in AIPC cells.
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Cell Line:PC3 or DU145 cells
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Concentration:20 nM
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Incubation Time:24 h
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Result:Attenuated the Oxaliplatin (1 μM)-induced NF-κB transcriptional activity and the increases in mRNA transcript levels for each of the CXC-chemokines (CXCL8 and CXCL1) and antiapoptotic genes (Bcl-2 and survivin) in the PC3 and DU145 cells.
AZ10397767 (compound 30a) has a CL of 4 ml/min/kg in rat[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SCID mice with A549 cells[4]
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Dosage:100 mg/kg
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Administration:Orally; twice daily; for 22 days
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Result:Tumors were 36% smaller than their control counterparts.
Significantly (p < 0.01) reduced the number of tumor-infiltrating neutrophils compared to mice receiving vehicle control.
Chemical Information
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CAS No. 333742-63-5
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Molecular Weight 400.88
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Formula C15H14ClFN4O2S2
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SMILES
O=C1SC2=C(N[C@H](C)CO)N=C(SCC3=CC=CC(Cl)=C3F)N=C2N1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Iain Walters, et al. Evaluation of a series of bicyclic CXCR2 antagonists. Bioorg Med Chem Lett. 2008 Jan 15;18(2):798-803. [Content Brief]
[2]. Angela Seaton, et al. Interleukin-8 signaling promotes androgen-independent proliferation of prostate cancer cells via induction of androgen receptor expression and activation. Carcinogenesis. 2008 Jun;29(6):1148-56. [Content Brief]
[3]. Catherine Wilson, et al. Chemotherapy-induced CXC-chemokine/CXC-chemokine receptor signaling in metastatic prostate cancer cells confers resistance to oxaliplatin through potentiation of nuclear factor-kappaB transcription and evasion of apoptosis. J Pharmacol Exp Ther. 2008 Dec;327(3):746-59. [Content Brief]
[4]. Simon Tazzyman, et al. Inhibition of neutrophil infiltration into A549 lung tumors in vitro and in vivo using a CXCR2-specific antagonist is associated with reduced tumor growth. Int J Cancer. 2011 Aug 15;129(4):847-58. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
AZ10397767 Related Classifications
HY-124056 Related Classifications
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