Drug intelligence / Profile preview

AP20187

Development stage
Unknown
Lead developer
Takeda
Modality
Small Molecules
Administration
Intraperitoneal (in Animal Models)
01

Overview

**AP20187** is a synthetic, cell-permeable, small-molecule chemical inducer of dimerization (CID) designed for research use in cell biology and gene therapy. It specifically induces homodimerization of engineered fusion proteins containing the F36V mutant of the FKBP domain (FKBPF36V)[1][7]. This dimerization is not reversible and, in the absence of engineered fusion partners, AP20187 itself is non-toxic to cells[2]. When used in engineered systems such as iCasp9, pro-apoptotic molecules (caspase-9, Fas, FADD, etc.), or chimeric receptors (e.g., LFv2IRE), AP20187 administration results in programmed cell death (apoptosis) or activation of intracellular signaling pathways mimicking endogenous hormones (e.g., insulin-like effects) in a controlled, dose-dependent manner[1][5]. AP20187 is widely used in research as a conditional cell elimination (“safety switch”) gene therapy tool, for example, to ablate engineered T cells in CAR-T therapies to manage toxicity[4]. It is also used to activate chimeric receptors in preclinical models of metabolic disease and in studies of cell fate control[5]. AP20187 is not an approved pharmaceutical agent; it is used exclusively in preclinical and laboratory research.

02

Targets

RET (Rearranged during transfection receptor tyrosine kinase)TRHR-FKBP12(F36V) (Thyrotropin-releasing hormone receptor-FKBP12(F36V) fusion protein)FKBP1A F36V (Peptidyl-prolyl cis-trans isomerase FKBP1A (FKBP12) engineered domain)MLL-FKBP (Histone-lysine N-methyltransferase 2A-FK506-binding protein fusion)iCasp9 (Inducible caspase-9)iFGFR1 (Inducible fibroblast growth factor receptor 1 fusion protein)

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