TDI-011536

TDI-011536 is a potent Lats kinase inhibitor, interrupts Hippo-Yap signaling and initiates the proliferation of lesioned heartmuscle cells. TDI-011536 can be used in studies of organ conservation and regeneration[1].

Research Areas >> Cardiovascular Disease

Research Areas >> Others

Signaling Pathways >> Stem Cell/Wnt >> YAP

Lats kinase[1].

TDI-011536 (3 µM; 24 h) reduces Yap phosphorylation and (3 µM; 5 days) induces proliferation of Müller glia in human retinal organoids[1]. Cell Proliferation Assay[1] Cell Line: human retinal organoids Concentration: 3 µM Incubation Time: 24 h, 5 days Result: Supressed Yap phosphorylation and promoted Müller glia proliferation.

TDI-011536 (200 mg/kg; i.p.; once) provides over 4 h of Lats inhibition in the liver, heart, and skin and reduces the amount of pYap for at least 4 h after injection in all three organs[1]. TDI-011536 (100 mg/kg; i.p.; once daily for 2 or 3 days) shows proliferative effect on cardiomyocytes[1]. Animal Model: Living mice (immunoblot analysis of the heart, liver, and skin immediately after injection)[1]. Dosage: 200 mg/kg Administration: Intraperitoneal injections; once. Result: Reduced the amount of pYap for at least 4 h after injection in all three organs and the levels returned to control values within a day. Animal Model: Male 8-week-old mice (cryolesion model)[1]. Dosage: 100 mg/kg Administration: Intraperitoneal injections; once daily for 2 or 3 days. Result: Promoted cardiomyocytes proliferation.

[1]. Kastan NR, et al. Development of an improved inhibitor of Lats kinases to promote regeneration of mammalian organs. Proc Natl Acad Sci U S A. 2022 Jul 12;119(28):e2206113119.