AP20187
AP20187 is a small dimerizer drug [1].
To solve the graft-versus-host disease, the in vivo behavior of the transplanted cells should be controlled. AP20187 is used in the conditional system as a chemical inducer of dimerization (CID). Another component is a fusion protein. The CIDs have advantages in gene therapy, it offers the possibility of achieving selection without the toxic effects. In vivo studies show that AP20187 can produces a notable expansion of transduced red cells, platelets, and to a lesser extent, granulocytes [1].
AP20187 is also reported to be used in an AP20187–LFv2IRE system. In this system, AP20187 administration causes the activation of LFv2IRE and results in increased uptake of both hepatic glycogen content and muscular glucose [2].
References:
[1] Neff T, Blau CA. Pharmacologically regulated cell therapy. Blood. 2001 May 1;97(9):2535-40.
[2] Cotugno G, Formisano P, Giacco F, Colella P, Beguinot F, Auricchio A. AP20187-mediated activation of a chimeric insulin receptor results in insulin-like actions in skeletal muscle and liver of diabetic mice. Hum Gene Ther. 2007 Feb;18(2):106-17.
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- 8. Adam L. Burrack, Zoe C. Schmiechen, et al. "Distinct myeloid antigen-presenting cells dictate differential fates of tumor-specific CD8+ T cells in pancreatic cancer." JCI Insight. 2022 Apr 8;7(7):e151593. PMID: 35393950
- 9. Colten Mitchell McEwan. "The Discovery of Novel 14-3-3 Binding Proteins ATG9A and PTOV1 and Their Role in Regulating Cancer Mechanisms." Brigham Young University. 2022.
- 10. Leila S Saleh, Luke D Amer, et al. "Mapping Macrophage Polarization and Origin during the Progression of the Foreign Body Response to a Poly (ethylene glycol) Hydrogel Implant." Adv Healthc Mater. 2021 Dec 30;e2102209. PMID: 34967497
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| Storage | Store at -20°C |
| M.Wt | 1482.75 |
| Cas No. | 195514-80-8 |
| Formula | C82H107N5O20 |
| Solubility | ≥74.14 mg/mL in DMSO; ≥100 mg/mL in EtOH |
| SDF | Download SDF |
| Canonical SMILES | O=C([C@@H]1CCCCN1C([C@@H](CC)C2=CC(OC)=C(OC)C(OC)=C2)=O)O[C@H](CCC3=CC(OC)=C(OC)C=C3)C4=CC=CC(OCC(NCC(CNC(COC5=CC=CC([C@@H](CCC6=CC(OC)=C(OC)C=C6)OC([C@H]7N(C([C@@H](CC)C8=CC(OC)=C(OC)C(OC)=C8)=O)CCCC7)=O)=C5)=O)CN(C)C)=O)=C4 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
CHO-AA8-Tet off cells |
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Preparation method |
The solubility of this compound in DMSO is >74.1mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
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Applications |
The cDNAs for the MLL-AF9 fusion protein were transfected in triplicate into CHO cells along with a Myc E box HSV TK luciferase reporter and a CMV-driven Renilla luciferase control plasmid. Results are expressed as a ratio of normalized firefly luciferase activity to the activity of cells transfected with an MSCV neomycin control vector. In the presence of the dimerizer AP20187, cells transfected with MLL-FKBP showed strong dose-dependent transactivation of the Myc E box HSV TK reporter. The dimerization of the fusion protein activated transcription with nearly 250-fold. |
| Animal experiment: [2] | |
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Animal models |
CD1 mice |
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Dosage form |
Intraperitoneal injection, 10 mg/kg |
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Applications |
To evaluate LFv2IRE expression and tyrosine phosphorylation, CD1 mice were injected via the tail vein with GC of AAV2/8-TBG-LFv2IRE or AAV2/1-MCK-LFv2IRE vector 4 weeks before the AP20187 injection. AP20187-dependent LFv2IRE tyrosine phosphorylation was evident 2 hr after drug administration, peaked 6 hr later, and returned to baseline after 24 hr. Low LFv2IRE basal phosphorylation was detected in liver samples from mice receiving AAV2/8-TBG-LFv2IRE but not stimulated with AP20187, suggesting minimal leakiness of the system. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Martin M E, Milne T A, Bloyer S, et al. Dimerization of MLL fusion proteins immortalizes hematopoietic cells. Cancer cell, 2003, 4(3): 197-207. [2] Cotugno G, Formisano P, Giacco F, et al. AP20187-mediated activation of a chimeric insulin receptor results in insulin-like actions in skeletal muscle and liver of diabetic mice. Human gene therapy, 2007, 18(2): 106-117. |
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| Description | AP20187 is a synthetic and cell-permeable drug that can dimerize and activate fusion proteins containing a growth factor receptor signaling domain. | |||||
| Targets | fusion proteins containing a growth factor receptor signaling domain | |||||
| IC50 | ||||||
Quality Control & MSDS
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Chemical structure
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