Cyclosporin H

Cyclosporin H is a selective and potent inhibitor of FPR-1 (formyl peptide receptor 1). Cyclosporin H, a viral transduction enhancer, increases lentiviral transduction up to 10-fold in human cord blood-derived hematopoietic stem and progenitor cells (HSPCs). Cyclosporin H displays an additive effect when combined with Rapamycin (HY-10219) or Prostaglandin E2 (HY-101952). Cyclosporin H lacks immunosuppressant activity of Cyclosporin A. In Vitro: The cyclic undecapeptide, cyclosporin H, is a potent inhibitor of formyl-Met-Leu-Phe (FMLP)-induced superoxide anion (O2-) formation in human neutrophils. Cyclosporin H inhibits FMLP binding in HL-60 membranes with a K_i of 0.1 μM. Cyclosporin H inhibits activation by FMLP of high affinity GTPase (the enzymatic activity of alpha-subunits of heterotrimeric regulatory guanine nucleotide-binding proteins) in HL-60 membranes with a K_i of 0.79 μM. Cyclosporin H inhibits the stimulatory effects of FMLP on cytosolic Ca²⁺ concentration ([Ca²⁺]i), O2- formation, and beta-glucuronidase release with K_i values of 0.08, 0.24, and 0.45 μM, respectively^[2]. In Vivo: Cyclosporin H (5 mg/kg; i.p.; before LPS or HCl challenge) attenuats lung injury induced by LPS or HCl (a lung injurymodel)^[1].