Varlitinib tosylate

Names

[ Name ]:
Varlitinib tosylate

[Synonym ]:
N-[3-Chloro-4-(1,3-thiazol-2-ylmethoxy)phenyl]-N-[(4R)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]-4,6-quinazolinediamine 4-methylbenzenesulfonate (1:2)
4,6-Quinazolinediamine, N-[3-chloro-4-(2-thiazolylmethoxy)phenyl]-N-[(4R)-4,5-dihydro-4-methyl-2-oxazolyl]-, 4-methylbenzenesulfonate (1:2)
Varlitinib tosylate

Biological Activity

[Description]:

Varlitinib (ASLAN001) tosylate is a potent, reversible, small molecule pan-EGFR inhibitor with IC50s of 7, 2, 4 nM for HER1, HER2 and HER4, respectively[1].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> EGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> EGFR

[Target]

IC50: 7 nM (HER1), 2 nM (HER2), 4 nM (HER4)[1]

[In Vitro]

在使用过度表达 EGFR (A431) 或 ErbB-2 (BT474) 的肿瘤细胞进行的基于细胞的测定中，Varlitinib tosylate (ARRY-334543) 有效抑制底物磷酸化。 Varlitinib tosylate 被证明对 EGFR/ErbB-2 具有高度选择性，并且在针对一组 104 种激酶进行筛选时未显示任何显着活性[2]。

[In Vivo]

Varlitinib tosylate 可有效抑制肿瘤生长，在每天两次 100 mg/kg 的剂量下可使肿瘤完全消退。Varlitinib tosylate 处理五天后，HER1-3、RAS/RAF/MEK/MAPK、p70S6K、S6 核糖体、4EBP1、Cdk-2、Cdc-2 和视网膜母细胞瘤的磷酸化受到强烈抑制。Varlitinib tosylate 处理导致生存素显着减少，同时 Caspase 3 裂解产物增加[1]。在小鼠异种移植模型中，Varlitinib tosylate（25、50、100 mg/kg）通过口服给药，每天两次，持续 21 天，在 A431 衍生肿瘤中表现出显着的剂量相关肿瘤生长抑制[2]。

[References]

[1]. Hsieh C, et al. Varlitinib to demonstrate anti-tumour efficacy in patient-derived hepatocellular carcinoma xenograft models. Journal of Clinical Oncology 34, no. 15_suppl

[2]. Miknis G, et al. ARRY-334543, A potent, orally active small molecule inhibitor of EGFR and ErbB-2.Proc Amer Assoc Cancer Res, Volume 46, 2005

Chemical & Physical Properties

[ Molecular Formula ]:
C₃₆H₃₅ClN₆O₈S₃

[ Molecular Weight ]:
811.35

[ Exact Mass ]:
810.136719

Related Compounds

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