生物活性

• 描述Toll-like receptors (TLRs) are a family of pattern recognition receptors involving in the innate and adaptive immunity. The activation of TLR7, which is intracellular receptor expressed on endosomal membranes, can induce Type 1 interferon and inflammatory response^[1]. Resiquimod is an immune system modifier as a TLR7 agonist with high potency induce cytokine expression for the treatment of viral and tumor lesions^[2]. The EC₅₀ of the resiquimod is 1.4 μM to TLR7^[3].
  Acute myeloid leukemia (AML) cells were treated with 5 μg/mL of resiquimod during 24 h. The expression of MHC class I and II molecules on the membrane of primary AML cells measured by flow cytometry and the production of IL-6, IL-1β and TNF-α measured by multiplex fluorescent bead immunoassay, were increased after the treatment with resiquimod^[4].
  The resiquimod were injected to BALB/c mice with breast cancer intraperitoneally for three continuous days in a week for three weeks. The resiquimod could significantly retard tumor growth compared with the vehicle group by reducing the density of tumor vasculature and inducing tumor cell apoptosis^[5].
• 作用机制The effect of resiquimod in the TLR signaling pathway is through binding to the TLR7. Therefore, it can activate the TLR7 mainly on dendritic cells, macrophages, and B-lymphocytes.
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  HEK293 cells	-	Function assay	-	Agonist activity at human TLR7 expressed in HEK293 cells coexpressing pNiFty2-SEAP reporter by reporter gene assay, EC50=0.2601 μM	20232824
  HEK293 cells	-	Function assay	24 h	Agonist activity at human TLR-7 expressed in HEK293 cells after 24 hrs by SEAP reporter gene assay, EC50=1.5 μM	24383475
  Huh7 replicon cells	-	Function assay	-	Antiviral activity against HCV infected human Huh7 replicon cells treated with drug-induced human PBMC supernatants assessed as viral levels by luciferase assay	17548497

• 更多

• 动物研究
  剂量	C57BL/6 Mice: 1 mg/kg[6] (intratracheally); 2 mg/kg[7] (i.v.) C3H/HeN Mice: 1 mg/kg - 5 mg/kg[8] (i.v.) BALB/c Mice: 3 mg/kg[5] (i.p.) Mice: 10 mg/kg[9] (i.p.), 2 mg/kg[10] (s.c.)
  给药途径	i.v., i.p., s.c.

• 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
  NCT02688478	Allergies	Not Applicable	Recruiting	May 7, 2020	Canada, British Columbia ... more >> University of British columbia Recruiting Vancouver, British Columbia, Canada, V5Z 1M9 Contact: Christopher Carlsten, MD, PHD    604-875-4122    carlsten@mail.ubc.ca    Principal Investigator: Christopher Carlsten, MD, MPH Collapse <<
  NCT02637219	-	-	Completed	-	United States, Washington ... more >> VA Puget Sound Health Care System Seattle, Washington, United States, 98108 Collapse <<
  NCT02687503	Respiratory Tract Infections	Not Applicable	Active, not recruiting	January 2019	United States, Wisconsin ... more >> UW Health 20 S. Park Clinic Madison, Wisconsin, United States, 53715 UW Health West Towne Clinic Madison, Wisconsin, United States, 53717 Collapse <<

• 更多
• 参考文献

• [1] Chi H, Li C, Zhao FS, et al. Anti-tumor Activity of Toll-Like Receptor 7 Agonists. Front Pharmacol. 2017.

  [2] Meyer T, Surber C, et al. Resiquimod, a topical drug for viral skin lesions and skin cancer. Expert Opin Investig Drugs. 2013;22(1):149-59.

  [3] Kubli-Garfias C, Vázquez-Ramírez R, et al. Insights on the mechanism of action of immunostimulants in relation to their pharmacological potency. The effects of imidazoquinolines on TLR8. PLoS One. 2017;12(6):e0178846.

  [4] Smits EL, Cools N, et al. The Toll-like receptor 7/8 agonist resiquimod greatly increases the immunostimulatory capacity of human acute myeloid leukemia cells. Cancer Immunol Immunother. 2010;59(1):35-46.

  [5] Yin T, He S, Wang Y. Toll-like receptor 7/8 agonist, R848, exhibits antitumoral effects in a breast cancer model. Mol Med Rep. 2015;12(3):3515-3520.

• 更多

• Collapse