TP-0184 (BMPR Signaling Inhibitor)
TP-0184 is an inhibitor of activin-like kinase 2 (ALK2), which is a bone morphogenetic protein receptor (BMPR) that activates SMAD transcription factors.1
ALK2 as a Potential Target
In chronic inflammatory conditions, ALK2 is constitutively activated due to proinflammatory cytokine signaling.2 This results in increased transcription of hepcidin, a peptide liver hormone that functions as a master regulator of serum iron levels, particularly in response to inflammation.2 The elevated levels of circulating hepcidin leads to low serum iron and anemia of chronic disease (ACD).1
TP-0184 has shown significant activity in decreasing hepcidin expression and restoring normal levels of hemoglobin through the inhibition of ALK2 in preclinical models of anemia driven by acute and chronic inflammation and by cancer. TP-0184 has been shown to lower liver and circulating hepcidin levels and to increase bioavailable iron levels in the serum.
TP-0184 represents a first-in-class ALK2 inhibitor with the potential to be an orally administered small molecule for the treatment of ACD.
TP-0184 is an investigational agent and is not approved by the US FDA or any other regulatory authorities.
References: 1. Peterson P, Kim W, Haws H, et al. The ALK-2 inhibitor, TP-0184, demonstrates high distribution to the liver contributing to significant preclinical efficacy in mouse models of anemia of chronic disease [Abstract]. Blood. 2016;128:263. 2. Peterson P, Soh KK, Lee YS, et al. ALK2 inhibition via TP-0184 abrogates inflammation-induced hepcidin expression and is a potential therapeutic for anemia of chronic disease [Abstract]. Blood. 2015;126:273. 3. Vyoral D, Petrak J. Therapeutic potential of hepcidin—the master regulator of iron metabolism. Pharmacol Res. 2017;115:242-254.