Biochem/physiol Actions
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.
AP20187是合成的且细胞可渗透的FK506（他克莫司）类似物，充当化学二聚体，二聚化（CID）的化学诱导剂，可逆地二聚化并激活包含生长因子受体信号转导DmrB结构域的融合蛋白。 它已被用来诱导细胞表面受体蛋白质的寡聚化，并研究任何受寡聚化影响的蛋白质的活性和/或重新定位。 已发现AP20187可以起到缓和作用。 在表达FK506结合蛋白-caspase 8（FKBP–Casp8）融合蛋白的转基因小鼠模型中，AP20187激活衰老细胞中FKBP融合的Casp8，导致细胞凋亡，导致肿瘤发生延迟，与年龄相关的器官退化减少， 并延长了使用寿命。
| Description | AP20187 (B/B Homodimerizer) is a cell-permeable ligand used to dimerize FK506-binding protein (FKBP) fusion proteins and initiate biological signaling cascades and gene expression or disrupt protein-protein interactions. |
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| In Vitro | When LNCaP cells are treated with AP20187 (B/B Homodimerizer) (100 nM), ro-iCaspase-9 levels are significantly reduced, and the smaller processed active caspase-9 becomes apparent[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only. |
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| In Vivo | Real-time PCR analysis shows that AP20187 (B/B Homodimerizer) (0.5 mg/kg, 2 mg/kg, or 5 mg/kg) treatment significantly increases the levels of CHOP mRNA in the CNS of PLP/Fv2E-PERK mice at PID12. AP20187 treatment significantly alleviates EAE-induced myelin damage in these mice. AP20187 (B/B Homodimerizer) treatment significantly reduces the number of degenerating axons and increases the density of axons in the demyelinating lesions in the lumbar spinal cord of PLP/Fv2E-PERK mice[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only. |
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| SMILES | COC1=C(OC)C=C(CC[C@H](C2=CC=CC(OCC(NCC(CN(C)C)CNC(COC3=CC=CC([C@H](OC([C@H]4N(C([C@@H](CC)C5=CC(OC)=C(OC)C(OC)=C5)=O)CCCC4)=O)CCC6=CC(OC)=C(OC)C=C6)=C3)=O)=O)=C2)OC([C@@H]7CCCCN7C([C@H](C8=CC(OC)=C(OC)C(OC)=C8)CC)=O)=O)C=C1 |
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| Shipping | Room temperature in continental US; may vary elsewhere. |
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| Storage | | Powder | -20°C | 3 years |
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| | 4°C | 2 years |
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| In solvent | -80°C | 6 months |
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| | -20°C | 1 month |
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| Solvent & Solubility | In Vitro: DMSO : ≥ 57 mg/mL (38.44 mM) * "≥" means soluble, but saturation unknown. Preparing
Stock Solutions | ConcentrationSolventMass | 1 mg | 5 mg | 10 mg |
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| 1 mM | 0.6744 mL | 3.3721 mL | 6.7442 mL | | 5 mM | 0.1349 mL | 0.6744 mL | 1.3488 mL | | 10 mM | 0.0674 mL | 0.3372 mL | 0.6744 mL |
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储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (1.69 mM); Clear solution 2. 请依序添加每种溶剂： 10% DMSO 90% corn oil Solubility: ≥ 2.5 mg/mL (1.69 mM); Clear solution
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| References | [1]. Ahmed S, et al. Photocleavable dimerizer for the rapid reversal of molecular trap antagonists. J Biol Chem. 2014 Feb 21;289(8):4546-52. [2]. Lin W, et al. Oligodendrocyte-specific activation of PERK signaling protects mice against experimental autoimmune encephalomyelitis. J Neurosci. 2013 Apr 3;33(14):5980-91. [3]. Haas ME, et al. The Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Nephrotic Syndrome-Associated Hypercholesterolemia. Circulation. 2016 Jul 5;134(1):61-72.
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