**Background**
Pulmonary arterial hypertension (PAH) is a severe progressive disease characterized by the remodeling of small pulmonary arteries, leading to increased pulmonary vascular resistance and right heart failure. A key driver of this pathological remodeling is the overactivation of various tyrosine kinases, particularly the platelet-derived growth factor receptors (PDGFRα and PDGFRβ), which promote the proliferation of pulmonary artery smooth muscle cells. Additionally, the loss of bone morphogenetic protein receptor type 2 (BMPR2) expression is frequently associated with the progression of PAH. Therefore, developing targeted therapies that can inhibit these proliferative pathways while restoring protective signaling is critical for improving patient outcomes. In this context, we will introduce an inhaled PDGFR inhibitor – Seralutinib.
**Definition**
Seralutinib (GB002) is an inhaled kinase inhibitor that targets PDGFRα and PDGFRβ, as well as CSF1R and c-KIT, with IC50 values of 8 nM for CSF1R and 14 nM for c-KIT.
**In Vitro and In Vivo Studies**
According to the Seralutinib description, this compound is designed for localized delivery to the lungs to minimize systemic exposure. Seralutinib in vitro data indicates that the compound effectively inhibits the phosphorylation of lung PDGFRα/β in healthy Sprague Dawley rats immediately following inhalation. Furthermore, Seralutinib has been shown to induce the expression of BMPR2 protein in the lung lobes in a dose- and time-dependent manner.
Regarding Seralutinib In Vivo activity, studies using the Su5416 hypoxia rat model of PAH demonstrated that a two-week treatment delivered by inhalation significantly reduces mean pulmonary artery pressure and right ventricular systolic pressure. These hemodynamic improvements are accompanied by a reduction in pulmonary arteriole muscularization and the restoration of BMPR2 protein expression. The compound was reported to be well tolerated during these studies. For researchers seeking detailed Seralutinib technical information, these results highlight the potential of the compound to reverse vascular remodeling. In conclusion, Seralutinib is a potent inhaled inhibitor of PDGFRα/β, CSF1R, and c-KIT that holds promise for the treatment of pulmonary arterial hypertension.
Keywords
Seralutinib, 1619931-27-9, GB002, PK10571, GB 002, GB-002, PK 10571, PK-10571, PDGFR, c-Fms, c-Kit, Platelet-derived growth factor receptor, CSF-1 receptor, colony stimulating factor 1 receptor, CSF-1R, CSF1R, SCFR, CD117, Pulmonary, arterial, hypertension, PAH, Inhibitor, inhibitor, inhibit
References
[1] Anna Galkin, et al. Abstract 11102: Gb002, A Novel Inhaled Pdgfr Kinase Inhibitor, Demonstrates Efficacy in the Su5416 Hypoxia Rat Model of Pulmonary Arterial Hypertension (pah). Circulation. 2019;140:A11102.
[2] Anna Galkin, et al. Pharmacologic Characterization of GB002, a Novel Inhaled PDGFR Kinase Inhibitor in Development for Pulmonary Arterial Hypertension (PAH).
[3] Robert P. Frantz1, et.al. Phase 2 Clinical Study to Evaluate the Efficacy and Safety of Inhaled GB002 (Seralutinib) for the Treatment of World Health Organization Group 1 Pulmonary Arterial Hypertension