SB225002

Meanwhile, SB225002 exerts directly antitumor activity and enhances the radiosensitivity of cervical cancer cells by facilitating DNA double-strand breaks, promoting G2/M phase cell cycle arrest, and inducing apoptosis. In summary, our findings highlight neutrophils inhibition via CXCR2 antagonist as a promising therapeutic strategy to enhance cervical cancer responsiveness to radiotherapy.

After intrathecal injection of the CXCR2 antagonist SB225002, the rats' pain threshold increased, accompanied by reduced expression of inflammatory factors and reversal of glial cell activation...Transfection with si-CXCR2 led to decreased expression of p-ERK and p-p38 in microglial cells, along with lower TNF-α and IL-1β levels in the cell supernatant. These results indicate that CXCR2 activates spinal glial cells via the ERK/p38 pathway, promoting neuroinflammation, and CPSP, whereas CXCR2 inhibition counteracts these effects and alleviates CPSP.

Pharmacological inhibition of CXCR2 using SB225002, a selective small-molecule antagonist, was evaluated to determine its effects on cell growth, colony formation, apoptosis, and cell cycle progression in different NB cell lines...This study provides strong evidence for elucidating CXCR2-targeted therapies as an attractive treatment option for NB. These findings support the development of CXCR2-targeted therapies for high-risk NB.

The effects of mogamulizumab and chemical antagonists of C-C/C-X-C chemokine receptors TAK-799, SB225002, and MK-7123 on SCI recovery in rodents are further estimated. Here blockade of CCR5 and CXCR1/2 chemokine receptors is shown beneficial for amelioration of acute SCI, whereas anti-CCR4 antibody mogamulizumab readily prevents secondary inflammation in the injured area. Summarizing, the current report claims for a novel combined time-resolved therapeutic modality in SCI treatment, which supports feasibility and motivates off-label clinical evaluation in appropriate cohorts.

CXCR2 knockdown or inhibition (using SB225002) reduced IL-8-induced upregulation of RASGRP4 mRNA and protein in THP-1 cells...In summary, the CXCL8-CXCR2 axis promotes M2 macrophage polarization via RASGRP4-mediated mTOR-STAT3 signaling in ovarian cancer. Targeting this pathway may be a promising therapeutic strategy to reprogram tumor-associated macrophages and enhance treatment efficacy.

Combining APM with a CXCR2 antagonist, SB225002, further inhibits bone metastasis progression. This study provides a high-resolution profile of vitamin C's antitumor effects in the bone metastatic microenvironment and supports the rationale for clinical trials of vitamin C in bone metastatic RCC.

It discusses anti-CXCL1 antibodies and CXCR2 antagonists, including AZD5069, SB225002, SCH-479833, navarixin/SCH-527123, ladarixin/DF2156A, and reparixin, as well as strategies to enhance CXCR2 expression in lymphocytes during adoptive cell therapy to improve immunotherapy outcomes. CXCR2 inhibitors are well tolerated by patients in clinical trials. However, the limited number of studies evaluating these agents in combination with standard chemotherapy precludes any definitive conclusions.

Interestingly, the same response in terms of inhibition of cell viability also occurs in the stromal compartment (normal fibroblasts): however, in this compartment, the G2/M block is non reversible, hence leading to non-apoptotic cell death. These findings suggest that SB225002 could be a potential therapeutic agent in colorectal cancer, by affecting not only cell viability, but also tumor-stroma interactions.

Combined treatment with the SB431542 and the SB225002 significantly attenuated LCN2-related CRC metastasis. Targeting the LCN2/TGFB1/CXCL5 axis emerges as a promising therapeutic strategy for managing LCN2-related metastatic CRC.

Our results underscore the significant role of the IL-8/CXCR2 signaling axis in the metastasis of TNBC and suggest that CXCR2 inhibitors such as SB225002 may be promising therapeutic agents for TNBC patients.

IL-8-derived tumor cells could upregulate ALDH1A1 expression by activating the NF-κB signaling pathway, promoting tumor progression. Upregulation of ALDH1A1 could activate NF-κB to promote IL-8 secretion, forming a positive feedback loop to promote tumor invasiveness and cell stemness in ICC.

In mice with pancreatic cancer-induced pain, the microglia activation in the NTS was observed, characterized by increased cell density and decreased process number and length, while injection of microglia inhibitor minocycline in the NTS alleviated pancreatic cancer-induced pain...Blocking CXCL1-CXCR2 signaling by injection of CXCL1 neutralizing antibody or CXCR2 antagonist SB225002 in the NTS of mice with pancreatic cancer-induced pain alleviated abdominal hypersensitivity and hunching behavior, and also reversed the activation of neurons and microglia. Additionally, injection of recombinant CXCL1 in the NTS of sham-operated mice induced abdominal pain, and activated the neurons and microglia. In summary, our study highlights the critical role of NTS microglia activation mediated by CXCL1-CXCR2 signaling in pancreatic cancer-induced pain.