SGK1 inhibitors to treat cardiovascular and neurodegenerative diseases

Selective SGK1 kinase inhibitors, blood-brain barrier-permeable, as drug candidates for the treatment of neurodegenerative diseases (such as Parkinson’s or Alzheimer’s disease) or cardiovascular diseases (such as hypertension).

Market need: Market needs for neurodegenerative and cardiovascular diseases focus on early diagnosis, disease-modifying and personalized therapies, and comprehensive patient-centered care.
SGK1 is a promising therapeutic target for drug development against these diseases, which involve a high degree of inflammation—particularly Parkinson’s and Alzheimer’s disease, or cardiovascular conditions such as arterial hypertension, pulmonary hypertension, or myocardial infarction.

Proposed solution: Indazole-derived compounds that selectively inhibit the SGK1 kinase and cross the blood-brain barrier (BBB). They have shown in vitro inhibition of recombinant SGK1 protein (IC50s 0.1–3 µM).
They exhibit neuroprotective effects in vitro and in vivo in a mouse model of Parkinson’s disease. Additionally, they reduce Tau protein phosphorylation in cells, demonstrating their potential for treating Alzheimer’s disease. Their protective effect has also been tested in cells and in a mouse model of arterial hypertension (induced by subcutaneous angiotensin II pumps), as well as in models of inflammation and pulmonary hypertension (induced by LPS and hypoxia).

Competitive advantages

They are neuroprotective against alpha-synuclein in a mouse model of Parkinson’s disease through chronic intraperitoneal administration.
Their efficacy has been demonstrated against inflammation and vascular damage in an in vivo mouse model of acute lung injury induced by LPS, as well as in models of arterial and pulmonary hypertension.
intraperitoneal or oral route administration. In vivo pharmacokinetic studies have been conducted using both oral and intraperitoneal administration.