Thi-DPPY

Thi-DPPY (compound 8e) is a potent and orally active JAK3 inhibitor with IC50 values of 62.4, 1.38 nM for BTK, JAK, respectively. Thi-DPPY shows anti-proliferative activity against HBE cells. Thi-DPPY shows anti-inflammatory activity in vivo. Thi-DPPY has the potential for the research of idiopathic pulmonary fibrosis (IPF)[1].

Signaling Pathways >> JAK/STAT Signaling >> JAK

Signaling Pathways >> Epigenetics >> JAK

Signaling Pathways >> Stem Cell/Wnt >> JAK

Research Areas >> Inflammation/Immunology

JAK3:1.38 nM (IC50)

BTK:62.4 nM (IC50)

DPPY (compound 8e) shows anti-proliferative activity against HBE (human bronchial epithelia) cells with an IC50 of 39.0 µM[1].

DPPY (30, 60 mg/kg; i.g., once daily for 14 days) shows anti-IPF agents on the lung morphology and lung coefficient in mouse model[1]. DPPY (30, 60 mg/kg) significantly decreases the expression of IL-6, IL-17A, TNF-α and MDA in lung tissue in a dose dependent manner[1]. Animal Model: 5-6 week old, 20-25 g, C57BL mice (BLM-induced pulmonary inflammation and pulmonary fibrosis model)[1] Dosage: 30, 60 mg/kg Administration: I.g.; once daily for 14 days Result: Attenuated the pulmonary morphology changes and reduced the collagen disposition induced by BLM in mouse lung.

[1]. Zhu Y, et al. Synthesis and biological activity of thieno[3,2-d]pyrimidines as potent JAK3 inhibitors for the treatment of idiopathic pulmonary fibrosis. Bioorg Med Chem. 2020 Jan 15;28(2):115254.