Version 1
: Received: 2 October 2024 / Approved: 3 October 2024 / Online: 4 October 2024 (04:18:48 CEST)
How to cite:
Araldi, G. L.; Hwang, Y.; Raghu, G. Development and Evaluation of ABI-171, a New Fluoro Catechin Derivative, for the Treatment of Idiopathic Pulmonary Fibrosis (IPF). Preprints2024, 2024100267. https://doi.org/10.20944/preprints202410.0267.v1
Araldi, G. L.; Hwang, Y.; Raghu, G. Development and Evaluation of ABI-171, a New Fluoro Catechin Derivative, for the Treatment of Idiopathic Pulmonary Fibrosis (IPF). Preprints 2024, 2024100267. https://doi.org/10.20944/preprints202410.0267.v1
Araldi, G. L.; Hwang, Y.; Raghu, G. Development and Evaluation of ABI-171, a New Fluoro Catechin Derivative, for the Treatment of Idiopathic Pulmonary Fibrosis (IPF). Preprints2024, 2024100267. https://doi.org/10.20944/preprints202410.0267.v1
APA Style
Araldi, G. L., Hwang, Y., & Raghu, G. (2024). Development and Evaluation of ABI-171, a New Fluoro Catechin Derivative, for the Treatment of Idiopathic Pulmonary Fibrosis (IPF). Preprints. https://doi.org/10.20944/preprints202410.0267.v1
Chicago/Turabian Style
Araldi, G. L., YuWen Hwang and Ganesh Raghu. 2024 "Development and Evaluation of ABI-171, a New Fluoro Catechin Derivative, for the Treatment of Idiopathic Pulmonary Fibrosis (IPF)" Preprints. https://doi.org/10.20944/preprints202410.0267.v1
Abstract
The persistent challenge of IPF, characterized by disease progression and high mortality, underscores the urgent need for innovative therapeutic strategies. We have developed a novel small molecule – catechin derivative ABI-171 – selectively targeting DYRK1A and PIM1 kinases, crucial in the pathogenesis of fibrotic processes. We employed the Bleomycin-induced (intratracheal) mouse model of pulmonary fibrosis (PF) to evaluate the therapeutic efficacy of ABI-171. Mice with induced PF were treated QD with ABI-171 either prophylactically or therapeutically using oral and intranasal routes. Pirfenidone (100mg/kg, TID) and Epigallocatechin gallate (EGCG, 100 mg/kg, QD), a natural catechin currently in a Phase 1 clinical trial, were used as reference compounds. ABI-171, administered prophylactically, led to a significant reduction in hydroxyproline levels and fibrotic tissue formation compared to the control group. Treatment with ABI-171 improved body weight, indicating mitigation of disease-related weight loss. Additionally, ABI-171 demonstrated anti-inflammatory activity, reducing lymphocyte and neutrophil infiltration. In the therapeutic setting, ABI-171, administered 7 days post-induction, reduced mortality rates (P = 0.04) compared with the bleomycin and EGCG control groups. ABI-171 also ameliorated the severity of lung injuries assessed by improved Masson’s trichrome scores when administered both orally and intranasally. ABI-171 significantly decreases bleomycin-induced PF and improves survival in mice, showcasing promising therapeutic potential beyond current medications like Pirfenidone and EGCG for patients with IPF. Based on these results, further studies with ABI-171 are ongoing in preclinical studies.
Keywords
EGCG; green tea; IPF; Bleomycin
Subject
Biology and Life Sciences, Life Sciences
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
