BI-113823 is an orally active, blood-brain barrier-permeable bradykinin B1 receptor antagonist, with a K i value of 5.3 nM for human receptors and 13.3 nM for rat receptors. BI-113823 reduces inflammation-induced mechanical hyperalgesia, as well as the mechanical sensitivity of peripheral afferent nerves and spinal nociceptive-specific neurons. BI-113823 alleviates liver fibrosis and portal hypertension, and improves survival in chronic liver disease models. BI-113823 inhibits the activities of monocytes, neutrophils and hepatic stellate cells, as well as the PI3K / Akt signaling pathway. BI-113823 can be used in research related to inflammatory pain, liver fibrosis and portal hypertension [1] [2].
In Vivo, BI-113823 (1-30 mg/kg; p.o.; single administration; 1-10 nM; intrathecal injection; single administration; 2.6 mg/kg; i.v.; single administration; 3.7 mg/kg/h; i.v.; continuous infusion) dose-dependently alleviates CFA -induced mechanical hyperalgesia, reducing the mechanical sensitivity of peripheral afferent nerves in rats to 45% of the baseline level at its maximal effect[1]. BI-113823 (50 mg/kg; p.o.; once daily; for 6 consecutive weeks) alleviates liver fibrosis and portal hypertension induced by CCl4 and bile duct ligation (BDL), and downregulates profibrotic and inflammatory mediators by inhibiting the Akt signaling pathway[2].
In Vitro, BI-113823 (10-7-10-6 M; 12 h) inhibits TNF-α-induced migration of human peripheral blood monocytes and human peripheral blood neutrophils in a dose-dependent manner[2]. BI-113823 (10-7-10-6 M) reduces LPS -induced TNF-α production in human peripheral blood mononuclear cells in a dose-dependent manner[2]. BI-113823 (10-100 nM) inhibits LPS-induced activation of human peripheral blood monocytes and human peripheral blood neutrophils, and reduces the expression level of CD11/CD18[2]. BI-113823 (10-7-10-6 M) reduces LPS-induced MPO activity in human peripheral blood neutrophils in a dose-dependent manner[2]. BI-113823 (1 μM; 24 h) inhibits TGF-β-induced α-SMA expression in LX2 human hepatic stellate cells[2]. BI-113823 (0-2 μM; 24 h) reduces the expression of TGF-β-stimulated profibrotic proteins and B1R, and inhibits the phosphorylation of Akt in human hepatic stellate cell line LX2[2]. BI-113823 (0.1-1 μM; 0-48 h) dose-dependently inhibits TGF-β-induced contraction of LX2 human hepatic stellate cells in collagen gels[2]. BI-113823 (0.1-1 μM; 12 h) inhibits the migration of 1% FBS-stimulated human hepatic stellate cell line LX2 in a dose-dependent manner[2]. BI-113823 (0.1-2 μM) inhibits DBK -induced scratch wound healing migration of human hepatic stellate cell line LX2 in a dose-dependent manner[2]. BI-113823 (0.001-1 μM) inhibits DBK-stimulated proliferation of human hepatic stellate cell line LX2 in a dose-dependent manner, without affecting baseline proliferation or inducing apoptosis[2]. BI-113823 (1 μM) inhibits G1-to-S phase cell cycle transition in human hepatic stellate cell line LX2 stimulated by DBK[2]. BI-113823 (1 μM) inhibits DBK-induced upregulation of B1R and activation of the PI3K/Akt and ERK signaling pathways in human hepatic stellate cell line LX2[2].
References:
[1]. Schuelert N, et al. The bradykinin B1 receptor antagonist BI113823 reverses inflammatory hyperalgesia by desensitization of peripheral and spinal neurons. Eur J Pain. 2015;19(1):132-142.
[2]. Rampa DR, et al. Kinin B1 receptor blockade attenuates hepatic fibrosis and portal hypertension in chronic liver diseases in mice. J Transl Med. 2022;20(1):590. Published 2022 Dec 13.
In Vivo, BI-113823 (1-30 mg/kg; p.o.; single administration; 1-10 nM; intrathecal injection; single administration; 2.6 mg/kg; i.v.; single administration; 3.7 mg/kg/h; i.v.; continuous infusion) dose-dependently alleviates CFA -induced mechanical hyperalgesia, reducing the mechanical sensitivity of peripheral afferent nerves in rats to 45% of the baseline level at its maximal effect[1]. BI-113823 (50 mg/kg; p.o.; once daily; for 6 consecutive weeks) alleviates liver fibrosis and portal hypertension induced by CCl4 and bile duct ligation (BDL), and downregulates profibrotic and inflammatory mediators by inhibiting the Akt signaling pathway[2].
In Vitro, BI-113823 (10-7-10-6 M; 12 h) inhibits TNF-α-induced migration of human peripheral blood monocytes and human peripheral blood neutrophils in a dose-dependent manner[2]. BI-113823 (10-7-10-6 M) reduces LPS -induced TNF-α production in human peripheral blood mononuclear cells in a dose-dependent manner[2]. BI-113823 (10-100 nM) inhibits LPS-induced activation of human peripheral blood monocytes and human peripheral blood neutrophils, and reduces the expression level of CD11/CD18[2]. BI-113823 (10-7-10-6 M) reduces LPS-induced MPO activity in human peripheral blood neutrophils in a dose-dependent manner[2]. BI-113823 (1 μM; 24 h) inhibits TGF-β-induced α-SMA expression in LX2 human hepatic stellate cells[2]. BI-113823 (0-2 μM; 24 h) reduces the expression of TGF-β-stimulated profibrotic proteins and B1R, and inhibits the phosphorylation of Akt in human hepatic stellate cell line LX2[2]. BI-113823 (0.1-1 μM; 0-48 h) dose-dependently inhibits TGF-β-induced contraction of LX2 human hepatic stellate cells in collagen gels[2]. BI-113823 (0.1-1 μM; 12 h) inhibits the migration of 1% FBS-stimulated human hepatic stellate cell line LX2 in a dose-dependent manner[2]. BI-113823 (0.1-2 μM) inhibits DBK -induced scratch wound healing migration of human hepatic stellate cell line LX2 in a dose-dependent manner[2]. BI-113823 (0.001-1 μM) inhibits DBK-stimulated proliferation of human hepatic stellate cell line LX2 in a dose-dependent manner, without affecting baseline proliferation or inducing apoptosis[2]. BI-113823 (1 μM) inhibits G1-to-S phase cell cycle transition in human hepatic stellate cell line LX2 stimulated by DBK[2]. BI-113823 (1 μM) inhibits DBK-induced upregulation of B1R and activation of the PI3K/Akt and ERK signaling pathways in human hepatic stellate cell line LX2[2].
References:
[1]. Schuelert N, et al. The bradykinin B1 receptor antagonist BI113823 reverses inflammatory hyperalgesia by desensitization of peripheral and spinal neurons. Eur J Pain. 2015;19(1):132-142.
[2]. Rampa DR, et al. Kinin B1 receptor blockade attenuates hepatic fibrosis and portal hypertension in chronic liver diseases in mice. J Transl Med. 2022;20(1):590. Published 2022 Dec 13.