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GNF-6231

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Chemical Structure| 1243245-18-2 同义名 : -
CAS号 : 1243245-18-2
货号 : A629360
分子式 : C24H25FN6O2
纯度 : 99%+
分子量 : 448.493
MDL号 : MFCD30343851
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 35 mg/mL(78.04 mM)，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 Wnt signaling is tightly controlled during cellular proliferation, differentiation, and embryonic morphogenesis. Aberrant activation of this pathway plays a critical role in a variety of cancers, such as cutaneous squamous cell carcinoma (SCC), breast cancer, and colorectal cancer[2]. GNF-6231 is a potent, selective, and orally bioavailable Porcupine inhibitor that blocks Wnt signaling with an IC50 value of 0.8 nM[2]. GNF-6231 shows IC50s of greater than 10 μM on all CYP (cytochromes P450) isoforms tested (2C9, 2D6, 3A4) and high permeability in a Caco-2 human cell permeability assay[2]. GNF-6231 is moderately bound to mouse, rat, dog, monkey, and human plasma proteins (88.0, 83.1, 90.9, 71.2, and 95%, respectively) as determined by rapid equilibrium dialysis. It shows good oral bioavailability, ranging from 72 to 96% in preclinical species (mouse, rat, and dog) when dosed in solution formulations. GNF-6231 is expected to have minimal to marginal distribution to tissues compared to total body water following intravenous administration to mouse (Vss 0.57 L/kg), rat (Vss 0.70 L/kg), and dog (Vss 0.25 L/kg). Treatment with GNF-6231 in MMTV-Wnt1 subcutaneously implanted tumor bearing mice led to pronounced inhibition of the Wnt signaling activity as measured by the reduction of Wnt target gene Axin2 expression[2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.23mL

0.45mL

0.22mL

11.15mL

2.23mL

1.11mL

22.30mL

4.46mL

2.23mL
参考文献

[1]Cheng D, Liu J, et al. Discovery of Pyridinyl Acetamide Derivatives as Potent, Selective, and Orally Bioavailable Porcupine Inhibitors. ACS Med Chem Lett. 2016 May 10;7(7):676-80.

[2]Cheng D, Liu J, Han D, Zhang G, Gao W, Hsieh MH, Ng N, Kasibhatla S, Tompkins C, Li J, Steffy A, Sun F, Li C, Seidel HM, Harris JL, Pan S. Discovery of Pyridinyl Acetamide Derivatives as Potent, Selective, and Orally Bioavailable Porcupine Inhibitors. ACS Med Chem Lett. 2016 May 10;7(7):676-80. doi: 10.1021/acsmedchemlett.6b00038. PMID: 27437076; PMCID:PMC4948009.