CXCL-CXCR1/2-IN-1 is an orally active ELR+CXCL-CXCR1/2 pathway inhibitor with an EC50 of 42.7 nM for CXCR2. CXCL-CXCR1/2-IN-1 shows anticancer and antiangiogenic effects.
In renal cell carcinoma (RCC) cell lines (A498, RCC4, 786, and Sunitinib-resistant RCC cell line 786-R) and neck squamous cell carcinoma (HNSCC) cell lines (CAL33, CAL27, Cisplatin- and radiotherapy-resistant cell lines CAL33RR and CAL27RR), CXCL-CXCR1/2-IN-1 (compound 10) shows IC50 values of 2 μM, 2 μM, 2.5 μM, 2 μM, 3 μM, 4 μM, 4 μM, 2.5 μM, and 2.5 μM against A498, RCC4, 786, 786-R, CAL33, CAL27, CAL33RR, and CAL27RR, respectively[1].CXCL-CXCR1/2-IN-1 inhibits the migration of A498 cancer cells in vitro[1]. CXCL-CXCR1/2-IN-1 (1-2.5 μM; 24-48 h) shows a reduction in the phosphorylation of ERK and AKT in A498 cells. CXCL-CXCR1/2-IN-1 also exhibits the capability to inhibit the secretion of CXCL1, CXCL5, and CXCL8, which are representative proangiogenic ELR+CXCL cytokines[1].
CXCL-CXCR1/2-IN-1 (1 μM; 48 h) reduces metastasis area in zebrafish embryos injected with A498 cells[1].CXCL-CXCR1/2-IN-1 (100 mg/kg; oral gavage; twice a day; for 28 days) inhibits tumor growth in mice[1].
References:
[1]. Oleksandr Grytsai, et al. A Potent Solution for Tumor Growth and Angiogenesis Suppression via an ELR+CXCL-CXCR1/2 Pathway Inhibitor. ACS Med. Chem. Lett. April 3, 2024.