1. Product Overview
AP20187 (CAS No. 195514-80-8), also known as B/B Homodimerizer, is a synthetic, cell‑permeable small‑molecule Chemical Inducer of Dimerization (CID) derived from FK506 (tacrolimus). It is engineered to selectively induce homodimerization of engineered fusion proteins containing the FKBP12 F36V mutant domain (FKBPF36V), enabling precise temporal and spatial control of protein–protein interactions in vitro and in vivo. By driving FKBP‑fused proteins to dimerize, AP20187 activates downstream signaling cascades such as chimeric insulin receptors, iCaspase‑9–mediated apoptosis, and conditional gene expression systems, making it a cornerstone reagent for chemically regulated cell therapy, senolytic studies, and signal transduction research.
2. Key Features and Advantages
• Cell‑Permeable & Bioactive: Readily crosses cell membranes to induce FKBPF36V homodimerization in living cells and animal models without requiring transfection.
• High Selectivity: Selective for FKBPF36V‑fused proteins over wild‑type FKBP, minimizing off‑target effects in native FKBP pathways.
• Reversible & Rapid Induction: Dimerization is rapid upon addition and reversible upon washout, allowing precise kinetic control of experimental conditions.
• Validated In Vivo Activity: Demonstrated efficacy in transgenic mice for inducing FKBP‑Casp8 apoptosis, expanding transduced hematopoietic cells, and activating chimeric insulin receptors to modulate hepatic glycogen and muscle glucose uptake.
• Excellent Solubility: Highly soluble in DMSO (≥74.14 mg/mL, ~100 mM) and ethanol (≥100 mg/mL), facilitating flexible stock preparation for cell‑based and animal studies.
• Research‑Grade Purity: ≥98% (HPLC), ensuring consistent and reproducible biological performance across assays.
3. Main Applications
• Conditional Gene Expression Systems: Temporal control of transcription factors or signaling domains fused to FKBPF36V, e.g., Myc‑E‑box luciferase reporter activation in CHO cells.
• Regulated Cell Therapy & Apoptosis Studies: Inducing iCaspase‑9 or FKBP‑Casp8 dimerization to trigger programmed cell death in engineered T cells, senolytic clearance of senescent cells, and graft‑versus‑host disease control.
• Signal Transduction & Receptor Dimerization: Mimicking natural receptor tyrosine kinase activation via chimeric insulin receptors (LFv2IRE system) to study glucose metabolism, hepatic glycogen storage, and muscle glucose uptake in diabetic mouse models.
• Protein–Protein Interaction Disruption/Assembly: Controlled oligomerization of surface receptors or intracellular scaffolds to dissect signaling nodes in cancer, autophagy, and metabolic research.
• In Vivo Pharmacologically Regulated Models: Used at 0.5–5 mg/kg in mice to drive dimerization‑dependent phenotypes in EAE, PERK signaling, and hematopoietic proliferation assays.
4. Technical Specifications
5. Storage and Handling
• Powder Storage: Store at -20°C, protected from light and desiccated. Stable for ~3 years at -20°C, ~2 years at 4°C in powder form.
• Solution Storage: Prepare fresh DMSO or ethanol stock solutions (≤100 mM). Aliquot and store at -80°C for up to 2 years or -20°C for up to 1 year; avoid repeated freeze–thaw cycles.
• Handling: Allow sealed vial to warm to room temperature before opening to prevent moisture condensation. Use DMSO pre‑warmed to 37°C with brief sonication if higher concentration stocks are needed. Prepare working solutions immediately before use; protect from light during experiments.
• Shipping: Blue‑ice recommended for long‑distance transport; evaluation samples can ship at ambient temperature with desiccant.
6. Safety Overview
• Intended Use: For laboratory research use only. Not for human or veterinary diagnostic/therapeutic use, nor for food or cosmetic applications.
• Hazard Profile: Non‑hazardous under normal handling; classified as combustible solid (WGK Germany 3). No specific GHS pictograms for research‑grade material, but handle as potentially bioactive small molecule.
• Precautions: Wear nitrile gloves, safety goggles, and lab coat. Avoid inhalation of dust, contact with skin/eyes, and ingestion. Use in a well‑ventilated area or fume hood when weighing powder.
• Disposal: Collect as chemical waste according to local regulations for organic small molecules; do not discharge into drains or environment.
• Additional Note: Cytotoxic/off‑target effects possible in cell culture at high concentrations; include vehicle (DMSO/EtOH) controls in all biological assays.
