AP20187 is a synthetic and cell-permeable FK506 (tacrolimus) analog that acts as a chemical dimerizer, a chemical inducer of dimerization (CID), to reversibly dimerize and activate fusion proteins containing a growth factor receptor signaling DmrB domain. It has been used to induce oligomerization of cell surface receptor proteins and to study the activity and/or re-localization of any protein that affected by oligomerization. AP20187 has been found to act as a senolytic. In a transgenic mouse model that expresses the FK506-binding protein–caspase 8 (FKBP–Casp8) fusion protein, AP20187 activated FKBP-fused Casp8 in senescent cells resulting in apoptosis of the cells resulting in delayed tumorigenesis , diminished age-related organ deterioration, and extended life span.
Synthetic and cell-permeable FK506 (tacrolimus) analog that acts as a dimerizer and activator of fusion proteins; senolytic
The Journal of biological chemistry, 278(19), 16466-16469 (2003-03-15)
Proteolytic activation of initiator procaspases is a crucial step in the cellular commitment to apoptosis. Alternative models have been postulated for the activation mechanism, namely the oligomerization or induced proximity model and the allosteric regulation model. While the former holds
Iatrogenic tumorigenesis is a major limitation for the use of human induced pluripotent stem cells (hiPSCs) in hematology. The teratoma risk comes from the persistence of hiPSCs in differentiated cell populations. Our goal was to evaluate the best system to
Cellular senescence, a stress-induced irreversible growth arrest often characterized by expression of p16(Ink4a) (encoded by the Ink4a/Arf locus, also known as Cdkn2a) and a distinctive secretory phenotype, prevents the proliferation of preneoplastic cells and has beneficial roles in tissue remodelling
