生物活性

• 描述SCH527123 is potent CXCR2/CXCR1 receptor antagonist with IC50 value of 2.6nM and 36nM for CXCR2 and CXCR1 receptor, respectively. It showed a displayed good oral bioavailability in rat. SCH527123 displayed superior inhibition of chemotaxis in vitro induced by CXCL1 or CXCL8 as it completely inhibited CXCL1-mediated neutrophil chemotaxis at 2nM. Pretreatment with SCH527123 for 5 min at concentration ranging in 1nM-10μM dose-dependently inhibited myeloperoxidase release by hPMN in response to CXCL8 (50 nM, 1 h at 37°C) . Oral administration of SCH 527123 blocked pulmonary neutrophilia as well as inhibiting goblet cell hyperplasia in mice following intranasal LPS challenge with ED50 values of 1.2 mg/kg and ~ 3 mg/kg, respectively.
• 作用机制SCH527123 is an allosteric antagonist.
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03473925	Solid Tumors ... more >>Non-small Cell Lung Cancer Castration Resistant Prostate Cancer Microsatellite Stable Colorectal Cancer Collapse <<	Phase 2	Recruiting	August 9, 2019	United States, Arizona ... more >> Honor Health ( Site 0005) Recruiting Scottsdale, Arizona, United States, 85258 Contact: Study Coordinator    623-238-7685       United States, Florida Florida Cancer Specialists ( Site 0003) Recruiting Sarasota, Florida, United States, 34232 Contact: Study Coordinator    941-377-9993       United States, Michigan Henry Ford Health System ( Site 0006) Recruiting Detroit, Michigan, United States, 48202 Contact: Study Coordinator    313-916-1784       United States, North Carolina Duke University Medical Center ( Site 0004) Recruiting Durham, North Carolina, United States, 27710 Contact: Study Coordinator    919-668-8797       Australia, New South Wales Scientia Clinical Research ( Site 0021) Recruiting Sydney, New South Wales, Australia, 2031 Contact: Study Coordinator    +61293825807       Australia, Victoria Peter MacCallum Cancer Centre ( Site 0023) Recruiting Melbourne, Victoria, Australia, 3000 Contact: Study Coordinator    +61385595000       Canada, Ontario Princess Margaret Cancer Centre ( Site 0031) Recruiting Toronto, Ontario, Canada, M5G 2M9 Contact: Study Coordinator    41694645015634       Canada, Quebec Jewish General Hospital ( Site 0032) Recruiting Montreal, Quebec, Canada, H3T 1E2 Contact: Study Coordinator    5143408222       Israel Sourasky Medical Center ( Site 0012) Recruiting Tel Aviv, Israel, 6423906 Contact: Study Coordinator    +97236973082       Korea, Republic of Severance Hospital Yonsei University Health System ( Site 0041) Recruiting Seoul, Korea, Republic of, 03722 Contact: Study Coordinator    +82222288132 Collapse <<
  NCT00632502	Neutrophilic Asthma	Phase 2	Completed	-	-
  NCT00684593	Psoriasis	Phase 2	Completed	-	-

• 更多
• 参考文献

• [1] Gonsiorek W, Fan X, et al. Pharmacological characterization of Sch527123, a potent allosteric CXCR1/CXCR2 antagonist. J Pharmacol Exp Ther. 2007 Aug;322(2):477-85.

  [2] Chapman RW, Minnicozzi M, et al. A novel, orally active CXCR1/2 receptor antagonist, Sch527123, inhibits neutrophil recruitment, mucus production, and goblet cell hyperplasia in animal models of pulmonary inflammation. J Pharmacol Exp Ther. 2007 Aug;322(2):486-93.