AP1903
(Synonyms: AP1903) 目录号 : GC15586
AP1903是一种二价"二聚化"化合物，可与FKBP结合并诱导Fas交联。
Cas No.:195514-63-7
Sample solution is provided at 25 µL, 10mM.
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AP1903 is a bivalent "dimerizer" compound that binds FKBP and induces Fas cross-linking[1]. AP1903 rapidly induces dimerization and activation of iC9, inducing apoptosis of the gene modified T cells[2]. AP1903 has been widely used to inhibit tumor growth and increase circulating inflammatory cytokine/chemokine levels[3].
In vitro, AP1903 treatment for 24 hours significantly inhibited the viability of H1 cells transfected with iC9 gene, with an IC50 value of 0.1242±0.0083nM[4]. Treatment with 100nM AP1903 for 15 days significantly promoted the expansion of MFM (MSCVF36Vmpl) retroviral vector transduced cord blood cells[5]. Treatment with 50nM AP1903 for 5 days caused morphological changes in SH-SY5Y cells transfected with pIRES2-iC9 vector and induced cell differentiation[6].
In vivo, AP1903 treatment via a single intraperitoneal injection at a dose of 5mg/kg for 9 days ameliorated colitis symptoms and improved survival in acute colitis mice infused with WJ-MSCiCasp9+/Luc+ cells[7]. Intravenous injection of AP1903 (5mg/kg/day for 5 days) immediately after intravenous injection of EF1α-iCasp9-hΔCD19 murine induced pluripotent stem cells (miPSCs) resulted in delayed teratoma growth in mice[8].
References:
[1] Thomis D C, Marktel S, Bonini C, et al. A Fas-based suicide switch in human T cells for the treatment of graft-versus-host disease[J]. Blood, The Journal of the American Society of Hematology, 2001, 97(5): 1249-1257
[2] Elkeky R, Jacobsohn D A, Agarwal R, et al. Administration of rimiducid following haploidentical BPX-501 cells in children with malignant or non-malignant disorders who develop graft-versus-host-disease (GvHD)[J]. Blood, 2018, 132: 2207.
[3] Stein M N, Dumbrava E E, Teply B A, et al. PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial[J]. Nature communications, 2024, 15(1): 10743.
[4] Wu Y, Chang T, Long Y, et al. Using gene editing to establish a safeguard system for pluripotent stem-cell-based therapies[J]. Iscience, 2019, 22: 409-422.
[5] Richard R E, Wood B, Zeng H, et al. Expansion of genetically modified primary human hemopoietic cells using chemical inducers of dimerization[J]. Blood, The Journal of the American Society of Hematology, 2000, 95(2): 430-436.
[6] Madadi Z, Akbari-Birgani S, Mohammadi S, et al. The effect of caspase-9 in the differentiation of SH-SY5Y cells[J]. European Journal of Pharmacology, 2021, 904: 174138.
[7] Romecín P A, Vinyoles M, López-Millán B, et al. Robust in vitro and in vivo immunosuppressive and anti-inflammatory properties of inducible caspase-9-mediated apoptotic mesenchymal stromal/stem cell[J]. Stem Cells Translational Medicine, 2022, 11(1): 88-96.
[8] Wu C, Hong S G, Winkler T, et al. Development of an inducible caspase-9 safety switch for pluripotent stem cell–based therapies[J]. Molecular therapy Methods & clinical development, 2014, 1.
AP1903是一种二价"二聚化"化合物，可与FKBP结合并诱导Fas交联[1]。AP1903能快速诱导iC9蛋白二聚化与激活，进而引发基因修饰T细胞的凋亡[2]。AP1903已广泛应用于抑制肿瘤生长及提升循环炎症因子/趋化因子水平的研究[3]。
在体外，AP1903处理24小时可显著抑制转染iC9基因的H1细胞活力，IC50值为0.1242±0.0083nM[4]。使用100nM的AP1903处理15天，能显著促进转导MFM (MSCVF36Vmpl) 逆转录病毒载体的脐血细胞扩增[5]。以50nM的AP1903处理转染pIRES2-iC9载体的SH-SY5Y细胞5天，可引起细胞形态改变并诱导细胞分化[6]。
在体内，单次腹腔注射5mg/kg剂量AP1903后9天，可改善输注WJ-MSCiCasp9+/Luc+细胞的急性结肠炎小鼠的临床症状并提高存活率[7]。在静脉注射EF1α-iCasp9-hΔCD19小鼠诱导多能干细胞（miPSCs）后立即静脉注射AP1903（5mg/kg/day），持续5日，能延缓小鼠畸胎瘤的生长[8]。
| Cell experiment [1]: | |
Cell lines | SH-SY5Y cells |
Preparation Method | SH-SY5Y cells (3×105) were plated in 6-well plates and transfected using a complex of polyethylenimine (PEI; 1mg/ml) and pIRES2-iC9 (4μg/well). Forty-eight hours after transfection, cells were treated with different concentrations of AP1903 (0, 5, 10, and 50nM). Cells were stained on day 5 after treatment, and then the morphological changes were assessed. |
Reaction Conditions | 0, 5, 10, and 50nM; 5 days |
Applications | AP1903 treatment significantly induced morphological changes of SH-SY5Y cells, with star-shaped characteristics. |
| Animal experiment [2]: | |
Animal models | Immunodeficient NSG mice |
Preparation Method | Immunodeficient NSG mice aged 4-8 weeks were maintained under standard conditions. 3×106 EF1α-iCasp9-hΔCD19 miPSCs were suspended in IMDM medium, mixed with Matrigel in a 1:1 ratio, and injected subcutaneously in a volume of 200μl into the mice. AP1903 (5mg/kg/day) was administered intravenously to the mice in a once-daily manner for 5 consecutive days, starting on the day of miPSC implantation. Tissue samples were taken from mice at the end of the experiment for analysis. |
Dosage form | 5mg/kg/day for 5 days; i.v. |
Applications | AP1903 treatment delayed teratoma growth caused by EF1α-iCasp9-hΔCD19 miPSCs in mice. |
References: | |
| Cas No. | 195514-63-7 | SDF | |
| 别名 | AP1903 | ||
| Canonical SMILES | O=C([C@@H](C(C=C1OC)=CC(OC)=C1OC)CC)N2[C@H](C(O[C@@H](C3=CC=CC(OCC(NCCNC(COC4=CC([C@H](CCC(C=C5OC)=CC=C5OC)OC([C@H]6N(C([C@@H](C(C=C7OC)=CC(OC)=C7OC)CC)=O)CCCC6)=O)=CC=C4)=O)=O)=C3)CCC(C=C8)=CC(OC)=C8OC)=O)CCCC2 | ||
| 分子式 | C78H98N4O20 | 分子量 | 1411.63 |
| 溶解度 | ≥ 23.5mg/mL in DMSO | 储存条件 | Store at -20°C,unstable in solution, ready to use. |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-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。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 708.4 μL | 3.542 mL | 7.084 mL |
| 5 mM | 141.7 μL | 708.4 μL | 1.4168 mL |
| 10 mM | 70.8 μL | 354.2 μL | 708.4 μL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
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Quality Control & SDS
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- Purity: >98.00%
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