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2,6-Dichloro-N-(2-(cyclopropanecarboxamido)pyridin-4-yl)benzamide

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Chemical Structure| 1258292-64-6 同义名 : GDC046
CAS号 : 1258292-64-6
货号 : A1325556
分子式 : C16H13Cl2N3O2
纯度 : 99%+
分子量 : 350.199
MDL号 : MFCD28155087
存储条件：

粉末 Inert atmosphere,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 60 mg/mL(171.33 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Janus kinase-signal transducer and activator of transcription (JAK-STAT) is an intracellular signaling pathway upon which many different proinflammatory signaling pathways converge[1]. JAK are a group of molecules, composed of JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2), which are key components within the JAK-signal transducers and activators of transcription pathway, where cytokine receptor signaling takes place. These molecules play a foundational role in the underlying pathogenesis of multiple immune-related conditions such as atopic dermatitis (AD), rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, and others[2]. The JAK/STAT signaling pathway is an universally expressed intracellular signal transduction pathway and involved in many crucial biological processes, including cell proliferation, differentiation, apoptosis, and immune regulation. It provides a direct mechanism for extracellular factors-regulated gene expression[3]. In skeletal muscle, activation of the JAK/STAT pathway by the IL-6 cytokines accounts for opposite effects: on the one hand, it promotes muscle hypertrophy, by increasing the proliferation of satellite cells; on the other hand, it contributes to muscle wasting. The expression of IL-6 and of key members of the JAK/STAT pathway is regulated at the epigenetic level through histone methylation and histone acetylation mechanisms[4].GDC046 (Compound 3) was an effective and selective oral biouse inhibitor of TYK2, with Ki values of 4.8 nM, 83.8 nM, 27.6 nM and 253 nM against TYK2, JAK1, JAK2 and JAK3, respectively[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.86mL

0.57mL

0.29mL

14.28mL

2.86mL

1.43mL

28.56mL

5.71mL

2.86mL
参考文献

[1] William Damsky,et al. JAK inhibitors in dermatology: The promise of a new drug class. J Am Acad Dermatol. 2017 Apr;76(4):736-744.

[2]Novin Nezamololama,et al.

[3] Ping Xin,et al. The role of JAK/STAT signaling pathway and its inhibitors in diseases. Int Immunopharmacol. 2020 Mar;80:106210.

[4] Viviana Moresi,et al. The JAK/STAT Pathway in Skeletal Muscle Pathophysiology. Front Physiol. 2019 Apr 30;10:500.

[5]Jun Liang, et al. J Med Chem. Lead optimization of a 4-aminopyridine benzamide scaffold to identify potent, selective, and orally bioavailable TYK2 inhibitors. 2013 Jun 13;56(11):4521-36.