BML-111

BML-111, a lipoxin A4 analog, is a lipoxin A4 receptor agonist. BML-111 represses the activity of angiotensin converting enzyme (ACE) and increases the activity of angiotensinconverting enzyme 2 (ACE2). BML-111 has antiangiogenic, antitumor and anti-inflammatory properties[1][2].

Research Areas >> Cancer

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Metabolic Enzyme/Protease >> Angiotensin-converting Enzyme (ACE)

Research Areas >> Inflammation/Immunology

Lipoxin A4 receptor[1] Angiotensin converting enzyme (ACE)[2]

In H22 cells, BML-111 inhibits the production of vascular endothelial growth factor and reduces hypoxia-inducible factor-1α level[1]. BML-111 inhibits leukotriene B4-induced cellular migration with an IC50 of 5 nM[3].

BML-111 (1 mg/kg; intraperitoneal injection; for 15 days; male Imprinting Control Region mice) treatment suppresses tumor-related angiogenesis and tumor growth in vivo. BML-111 also enhances the in situ apoptosis while inhibiting macrophage infiltration in tumor tissue[1]. BML-111 protects LPS-induced acute lung injury and LPS/D-GalN-induced acute liver injury. BML-111 represses the activity of ACE, but increases the activity of ACE2. BML-111 decreases the expression levels of ACE, AngII, and AngII type 1 receptor (AT1R), meanwhile increases the levels of ACE2, angiotensin-(1-7) (Ang-1-7), and Mas[2]. Animal Model: Male Imprinting Control Region mice (5-6-week-old,18-22 g) injected with H22 cells[1] Dosage: 1 mg/kg Administration: Intraperitoneal injection; injected 5 minutes before and 4 hours after H22 cell inoculation, then every 12 hours for 2 consecutive days, then daily in an additional 3 days and every other day for the last 10 days Result: Suppressed tumor-related angiogenesis and tumor growth in vivo.

[1]. Ying Chen, et al. Lipoxin A4 and Its Analogue Suppress the Tumor Growth of Transplanted H22 in Mice: The Role of Antiangiogenesis. Mol Cancer Ther. 2010 Aug;9(8):2164-74.

[2]. Qiong-Feng Chen, et al. BML-111, a Lipoxin Receptor Agonist, Protects Against Acute Injury via Regulating the Renin Angiotensin-Aldosterone System. Prostaglandins Other Lipid Mediat. 2019 Feb;140:9-17.

[3]. T H Lee, et al. Inhibition of Leukotriene B4-induced Neutrophil Migration by Lipoxin A4: Structure-Function Relationships. Biochem Biophys Res Commun. 1991 Nov 14;180(3):1416-21.