1404231-34-0

1404231-34-0 structure

Name: ON 146040
Chemical Name: ON 146040
CAS Number: 1404231-34-0
Molecular Formula: C₂₄H₂₃N₇O₃S
Molecular Weight: 489.55
Catalog: Signaling Pathways Protein Tyrosine Kinase/RTK Bcr-Abl
Create Date: 2018-06-21 19:37:28
Modify Date: 2024-01-12 17:00:03
ON 146040 is a potent PI3Kα and PI3Kδ (IC50≈14 and 20 nM, respectively) inhibitor. ON 146040 also inhibits Abl1 (IC50<150 nM).

Name	ON 146040

Description	ON 146040 is a potent PI3Kα and PI3Kδ (IC50≈14 and 20 nM, respectively) inhibitor. ON 146040 also inhibits Abl1 (IC50<150 nM).
Related Catalog	Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Bcr-Abl Research Areas >> Cancer
Target	PI3Kα:14 nM (IC50) PI3Kδ:20 nM (IC50) PI3Kγ:1 μM (IC50) PI3Kβ:3 μM (IC50) Abl1:150 nM (IC50)
In Vitro	In biochemical testing, ON 146040 inhibits PI3Kα/ PI3Kδ isoforms (IC50≈14 and 20 nM, respectively) without having a major effect on PI3Kβ/ PI3Kγ isoforms (IC50≈3 and 1 μM, respectively). ON 146040 is also found to inhibit Abl1 and several mutant versions of this kinase (IC50<150 nM), although ON 146040 is not found to be active against the T315I mutant. ON 146040 represents the first dual PI3K and BCR-ABL inhibitor that targets the STAT3 and STAT5 pathways. ON 146040 disrupts the oncogenic activity of both STAT3 and STAT5 by targeting upstream activators, including PI3K α and δ isoforms as well as wild type and mutant BCR-ABL. ON 146040 is highly potent in killing hematologic tumor cells with IC50 values in the 150 to 1,000 nM range. Following treatment with ON 146040, STAT3 and STAT5 phosphorylation are down-regulated in leukemia and myeloma cells[1].
References	[1]. Targeting oncogenic STAT3 and STAT5 signaling with on 146040, a small molecule inhibitor of PI3K α/δ and BCR-ABL.