AZ10397767 是一种具有口服活性的、选择性CXCR2受体拮抗剂，IC50为 1 nM。AZ10397767 减弱 Oxaliplatin (HY-17371) 诱导的 NF-κB 转录活性并增强 Oxaliplatin 诱导的雄激素非依赖性前列腺癌 (AIPC) 细胞凋亡。AZ10397767 显着抑制中性粒细胞募集到肿瘤中，从而在体外和体内对肿瘤生长产生不利影响。
| 生物活性 | AZ10397767 is an orally active, selectiveCXCR2receptorantagonist with anIC50of 1 nM. AZ10397767 attenuates the Oxaliplatin (HY-17371)-inducedNF-κBtranscriptional activity and potentiates Oxaliplatin-inducedapoptosisin androgen-independent prostatecancer(AIPC) cells. AZ10397767 significantly inhibits neutrophil recruitment into tumors which then adversely affects tumor growth in vitro and in vivo[1][2][3][4]. |
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体外研究
(In Vitro) | AZ10397767 (20 nM; 48小时) 消除 IL-8 (3 nM) 诱导的细胞增殖，将细胞数量减少至基础水平以下[2]。
AZ10397767 (20 nM; 72小时) 增加 Oxaliplatin (HY-17371) 的细胞毒性，并增强 Oxaliplatin 诱导的 AIPC 细胞凋亡。AZ10397767 本身不能诱导 PC3 或 DU145 细胞凋亡[3]。
AZ10397767 (20 nM; 24小时) 减弱 Oxaliplatin 诱导的 NF-κB 转录活性，减弱 PC3 和 DU145 细胞中每种 CXC 趋化因子 (CXCL8 和 CXCL1) 和抗凋亡基因 (Bcl-2 和生存素) 的 mRNA 转录水平的增加[3]。
Cell Proliferation Assay[2] | Cell Line: | LNCaP cells and 22Rv1 cells | | Concentration: | 20 nM | | Incubation Time: | 48 h | | Result: | Abrogated the IL-8-induced (3 nM) increase in proliferation, reducing cell number to below basal levels. |
Apoptosis Analysis[3] | Cell Line: | PC3 or DU145 cells | | Concentration: | 20 nM | | Incubation Time: | 72 h | | 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. |
RT-PCR[3] | Cell Line: | PC3 or DU145 cells | | Concentration: | 20 nM | | Incubation Time: | 24 h | | 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. |
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体内研究
(In Vivo) | AZ10397767 (100 mg/kg; 口服灌胃; 每天两次; 持续 22 天) 在 A549 异种移植肿瘤中表现出中性粒细胞浸润减少并伴有肿瘤生长迟缓[4]。
AZ10397767 (化合物 30a) 在大鼠中的 CL 为 4 ml/min/kg[1]。
| Animal Model: | SCID mice with A549 cells[4] | | Dosage: | 100 mg/kg | | Administration: | Orally; twice daily; for 22 days | | 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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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