2024/3/15

WIKIMOLE—CHIR-99021 

CHIR-99021, catalog number: T2310, also known as Laduviglusib or CT99021, is a highly selective inhibitor of GSK-3α/β (Glycogen synthase kinase 3), with IC50 values of 10 nM and 6.7 nM, respectively. It is also an effective activator of the Wnt/β-catenin signaling pathway. Additionally, CHIR-99021 can induce autophagy and enhance self-renewal in mouse and human embryonic stem cells.

CHIR-99021 HCl, catalog number: T2310L, is the hydrochloride salt form of CHIR-99021.

Background

GSK-3 is a serine/threonine protein kinase found in mammals in two homologous isoforms, GSK-3α and GSK-3β. GSK-3 is involved in various cellular signaling pathways, including the mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and WNT/β-catenin pathways. It plays crucial roles in cellular metabolism, proliferation, differentiation, apoptosis, protein synthesis and transcription, as well as glucose metabolism and other biological activities. In recent years, GSK-3 has been a focus of research for many scientists due to its association with several diseases, including type 2 diabetes, Alzheimer's disease, inflammation, cancer, addiction, and bipolar disorder.

Application

CHIR-99021 is a highly selective inhibitor of GSK-3α/β, which are regulators of the Wnt signaling pathway. By inhibiting GSK-3α/β, CHIR-99021 promotes the activation of the Wnt signaling pathway, thereby influencing the self-renewal and differentiation of stem cells. For example, human pluripotent stem cell (hPSC)-derived organoids such as Heart Forming Organoids (HFOs) represent a complex, highly structured in vitro model of early heart, gut, and vascular system development. These organoids are commonly used in teratogenic research, gene function analysis, and drug discovery studies. CHIR-99021 and IWP2 (Catalog No. T2702) are typically used during the establishment of this model for cell differentiation.

As research progresses, scientists have found that CHIR-99021 significantly enhances the quantity and functionality of stem cells, showing promising applications across various stem cell types. The scope of CHIR-99021's applications continues to expand. Apart from its use in the field of stem cells, CHIR-99021 also demonstrates potential therapeutic value in neurodegenerative diseases, tumors, and metabolic disorders. In neurodegenerative diseases, CHIR-99021 can inhibit the generation and aggregation of beta-amyloid proteins, thereby slowing the progression of conditions like Alzheimer's disease. In the field of tumors, CHIR-99021 can modulate tumor cell proliferation and apoptosis, inhibiting tumor growth and metastasis. Additionally, CHIR-99021 can improve symptoms of metabolic disorders such as diabetes and obesity, promoting metabolic balance in the body.