Avatrombopag (AKR-501) 是一种口服活性的非肽血小板生成素受体(TPO receptor)激动剂 (EC50=3.3 nM)。Avatrombopag 可模拟 TPO 的生物活性。Avatrombopag hydrochloride 通过激活细胞内信号传导系统来增加血小板的产生，并促进造血前体细胞产生血小板和巨核细胞。Avatrombopag是细胞色素 P450 (CYP) 2C9 和 CYP3A 的底物。
| 生物活性 | Avatrombopag (AKR-501) is an orally active, nonpeptidethrombopoietin (TPO) receptoragonist (EC50=3.3 nM). Avatrombopag mimics the biological activities of TPO. Avatrombopag increases platelet production by activating the intracellular signaling system, and promotes production of platelets and megakaryocytes from hemopoietic precursor cells. Avatrombopag is a substrate ofcytochrome P450(CYP) 2C9 and CYP3A[1][2][3]. |
| IC50& Target | EC50: 3.3 nM (TPO receptor)[1] |
体外研究
(In Vitro) | Avatrombopag (E5501; AKR-501) specifically targets the TPO receptor and stimulated megakaryocytopoiesis throughout the development and maturation of megakaryocytes just as recombinant human TPO (rhTPO) did[1].
Avatrombopag (0-100 nM) supports the proliferation of TPO receptor expressing Ba/F3 cell in a concentration-dependent fashion. Avatrombopag (0-3 μM) induces tyrosine phosphorylation of STAT3 and STAT5, and threonine phosphorylation of ERK in the cells, as did rhTPO[1].
Avatrombopag promotes megakaryocyte colony formation from human CB CD34+cells in a concentration-dependent fashion. The EC50is 25 nM for Avatrombopag and the maximum activity of Avatrombopag is similar to that of rhTPO[1].
Cell Proliferation Assay[1] | Cell Line: | Ba/F3 cells | | Concentration: | 0.003 μM, 0.03 μM, 0.3 μM, 3 μM | | Incubation Time: | | | Result: | Increased the proliferation of TPO receptor expressing Ba/F3 cell in a concentration-dependent fashion. |
Western Blot Analysis[1] | Cell Line: | Ba/F3 cells | | Concentration: | 0.003 μM, 0.03 μM, 0.3 μM, 3 μM | | Incubation Time: | 15 minutes | | Result: | Induced tyrosine phosphorylation of STAT3 and STAT5, and threonine phosphorylation of ERK in the cells. |
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体内研究
(In Vivo) | Avatrombopag (0.3-3 mg/kg; p.o.; daily for 14 days) increases the number of human platelets in NOD/SCID mice transplanted with human FL CD34+cells[1].
| Animal Model: | NOD/SCID mice (transplanted with human FL CD34+cells)[1] | | Dosage: | 0.3, 1, and 3 mg/kg | | Administration: | P.o.; daily for 14 days | | Result: | Dose-dependently increased the number of human platelets, resulting in approximately a 2.7‐fold increase at 1 mg/kg/d and a 3.0-fold increase at 3 mg/kg/d on day 14 after the start of administration. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 8.33 mg/mL(12.82 mM;ultrasonic and warming and heat to 60℃) 配制储备液 | 1 mM | 1.5393 mL | 7.6965 mL | 15.3929 mL | | 5 mM | 0.3079 mL | 1.5393 mL | 3.0786 mL | | 10 mM | 0.1539 mL | 0.7696 mL | 1.5393 mL |
*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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 |
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