The activin type 2 receptors belong to a larger TGF-beta receptor family and modulate signals for transforming growth factor beta ligands. These receptors are involved in a host of physiological processes including, growth, cell differentiation, homeostasis, osteogenesis, apoptosis and many other functions.

We have developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) to prevent binding of ligands to the receptors and thus inhibit downstream signaling.

Mar 20, 2023 · We have developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) to prevent binding of ligands to the receptors and thus inhibit downstream signaling.

MSTN signaling is exerted downstream from activin type II receptors (ACTRII); after binding ACTRIIA/B, ACTRII couples with a type 1 receptor kinase (ACTRIB or TGFBRI) and activates signaling via SMAD2,3 transcription factors.

Prior studies suggested that canonical Activin Receptor II (ActRII) and BMP receptor (BMPR) ligands can have opposing, distinct effects on skeletal muscle depending in part on differential downstream SMAD activation.

Mar 15, 2019 · The activin receptor type 2 (ACTRII) pathway is activated in ageing and heart failure (HF), and inhibition of this catabolic pathway is a potential therapeutic target for HF.

Bimagrumab is under evaluation for muscle wasting and associated functional loss in hip fracture and sarcopenia, and in obesity. Bimagrumab also blocks other endogenous ActRII ligands, such as activins, which act on the neurohormonal axes, pituitary, gonads and adrenal glands.

Feb 1, 2020 · ACTRII/TGFBR signaling inhibition preserved cardiac function by echocardiography and prevented an increase in brain natriuretic peptide (BNP). ACTRII/TGFBR inhibition resulted in increased phosphorylation (P) of Akt and decreased P-p38 mitogen-activated protein kinase (MAPK) in MI mice.

We identified a key mechanism by which ActRII signaling regulates CM function through proteasome-mediated degradation of SERCA2a and present evidence with clinical-stage inhibitors that targeted ActRII blockade can restore cardiac function in HF.

May 30, 2024 · For instance, Activin A first binds to Activin RII (ActRII), then recruits and activates Activin RI (ActRI), forming a heteromeric complex. This complex subsequently transmits signals to the nucleus via pathways like SMAD2/3, ERK, p38, and PI3K.