Unilateral Nephrectomized SHR/NDmcr-cp Rat Shows a Progressive Decline of Glomerular Filtration With Tubular Interstitial Lesions

Shinozaki, Yuichi; Fukui, Kenji; Maekawa, Masato; Toyoda, K; Yoshiuchi, Hiromi; Inagaki, Kenichi; Uno, Keikichi; Miyajima, Katsuhiro; Ohta, Takeshi

doi:10.33549/physiolres.934969

Cited by 2 publications

(1 citation statement)

References 35 publications

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“…The result showed that the administration of 33 tended to reduce the plasma creatinine levels compared to vehicle group, suggesting that 33 has renoprotective potential. Therefore, we will conduct a long-term administration in a renal disease model such as the diabetic kidney disease (DKD) model we have reported …”

Section: Resultsmentioning

confidence: 99%

Optimization Efforts for Identification of Novel Highly Potent Keap1-Nrf2 Protein–Protein Interaction Inhibitors

Otake,

Hara,

Ubukata

et al. 2024

J. Med. Chem.

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In research focused on protein−protein interaction (PPI) inhibitors, the optimization process to achieve both high inhibitory activity and favorable physicochemical properties remains challenging. Our previous study reported the discovery of novel and bioavailable Keap1-Nrf2 PPI inhibitor 8 which exhibited moderate in vivo activity in rats. In this work, we present our subsequent efforts to optimize this compound. Two distinct approaches were employed, targeting high energy water molecules and Ser602 as "hot spots" from the anchor with good aqueous solubility, metabolic stability, and membrane permeability. Through ligand efficiency (LE)-guided exploration, we identified two novel inhibitors 22 and 33 with good pharmacokinetics (PK) profiles and more potent in vivo activities, which appear to be promising chemical probes among the existing inhibitors.

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Section: Resultsmentioning

confidence: 99%

Optimization Efforts for Identification of Novel Highly Potent Keap1-Nrf2 Protein–Protein Interaction Inhibitors

Otake,

Hara,

Ubukata

et al. 2024

J. Med. Chem.

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Animal Models of Kidney Disease: Challenges and Perspectives

Liang

Liu

2023

Kidney360

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Kidney disease is highly prevalent and affects about 850 million people worldwide. It is also associated with high morbidity and mortality, and current therapies are incurable and often ineffective. Animal models are indispensable for understanding the pathophysiology of various kidney diseases and for preclinically testing novel remedies. In the last two decades, rodents continue to be the most used models for imitating human kidney diseases, largely due to the increasing availability of many unique genetically modified mice. Despite many limitations and pitfalls, animal models play an essential and irreplaceable role in gaining novel insights into the mechanisms, pathologies and therapeutic targets of kidney disease. In this review, we highlight commonly used animal models of kidney diseases by focusing on experimental acute kidney injury, chronic kidney disease, and diabetic kidney disease. We briefly summarize the pathological characteristics, advantages and drawbacks of some widely used models. Emerging animal models such as mini-pig, salamander, zebrafish and drosophila, as well as human-derived kidney organoids and kidney-on-a-chip are also discussed. Undoubtedly, careful selection and utilization of appropriate animal models is of vital importance in deciphering the mechanisms underlying nephropathies and evaluating the efficacy of new treatment options. Such studies will provide a solid foundation for future diagnosis, prevention and treatment of human kidney diseases.

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Unilateral Nephrectomized SHR/NDmcr-cp Rat Shows a Progressive Decline of Glomerular Filtration With Tubular Interstitial Lesions

Cited by 2 publications

References 35 publications

Optimization Efforts for Identification of Novel Highly Potent Keap1-Nrf2 Protein–Protein Interaction Inhibitors

Optimization Efforts for Identification of Novel Highly Potent Keap1-Nrf2 Protein–Protein Interaction Inhibitors

Animal Models of Kidney Disease: Challenges and Perspectives

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