1. Immunology/Inflammation
  2. Thrombopoietin Receptor
  3. Avatrombopag hydrochloride

Avatrombopag hydrochloride (Synonyms: AKR-501 hydrochloride; E5501 hydrochloride; YM477 hydrochloride)

目录号: HY-13463B 纯度: 98.05%
产品使用指南

Avatrombopag (AKR-501) hydrochloride 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 hydrochloride 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 hydrochloride 是细胞色素 P450 (CYP) 2C9 和 CYP3A 的底物。

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Avatrombopag hydrochloride Chemical Structure

Avatrombopag hydrochloride Chemical Structure

CAS No. : 570403-17-7

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Description

Avatrombopag (AKR-501) hydrochloride is an orally active, nonpeptide thrombopoietin (TPO) receptor agonist (EC50=3.3 nM). Avatrombopag hydrochloride mimics the biological activities of TPO. Avatrombopag hydrochloride increases platelet production by activating the intracellular signaling system, and promotes production of platelets and megakaryocytes from hemopoietic precursor cells. Avatrombopag hydrochloride is a substrate of cytochrome P450 (CYP) 2C9 and CYP3A[1][2][3].

In Vitro

Avatrombopag (E5501; AKR-501) hydrochloride specifically targets the TPO receptor and stimulated megakaryocytopoiesis throughout the development and maturation of megakaryocytes just as recombinant human TPO (rhTPO) did. Avatrombopag hydrochloride is showed to have effect in humans and chimpanzees only[1].
Avatrombopag hydrochloride (0-100 nM) supports the proliferation of TPO receptor expressing Ba/F3 cell in a concentration-dependent fashion. Avatrombopag hydrochloride (0-3 μM) induces tyrosine phosphorylation of STAT3 and STAT5, and threonine phosphorylation of ERK in the cells, as did rhTPO[1].
Avatrombopag hydrochloride promotes megakaryocyte colony formation from human CB CD34+ cells in a concentration-dependent fashion. The EC50 is 25 nM for Avatrombopag hydrochloride and the maximum activity of Avatrombopag hydrochloride is similar to that of rhTPO[1].

In Vivo

Avatrombopag hydrochloride (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.
Molecular Weight

686.12

Formula

C₂₉H₃₅Cl₃N₆O₃S₂

CAS No.

570403-17-7

SMILES

O=C(C1CCN(C2=NC=C(C(NC3=NC(C4=CC(Cl)=CS4)=C(N5CCN(C6CCCCC6)CC5)S3)=O)C=C2Cl)CC1)O.Cl

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
References
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Keywords:

AvatrombopagAKR-501E5501YM477AKR501AKR 501E 5501E-5501YM 477YM-477Thrombopoietin ReceptormimicTPOmegakaryocytopoiesismegakaryocytesphosphorylationproliferationNOD/SCIDInhibitorinhibitorinhibit

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产品名称:
Avatrombopag hydrochloride
目录号:
HY-13463B
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