Glasdegib (PF-04449913) 是一种有效的

Glasdegib  (Synonyms: PF-04449913)

Glasdegib (PF-04449913) 是一种有效的，具有口服活性的 smoothened 抑制剂。Glasdegib (PF-04449913) 结合到人 SMO (181-787氨基酸位点)，IC₅₀ 为 4 nM。

美国medchemexpress（MCE)浙江省一级代理:杭州昊鑫生物科技股份有限公司
MCE中国是全球领先的科研化学品和生物活性化合物供应商，总部位于美国新泽西。我们的产品范围覆盖各种抑制剂、激动剂、API和化合物库。专业、高效的企业灵魂铸造了在行业的卓越地位。热情和充满活力的研发团队拥有着大量的化学和生物科学家。专注于生物活性化合物，拥有着多年的发展历程和丰富的行业经验。

生物活性    
Glasdegib (PF-04449913) is a potent and orally bioavailable smoothened inhibitor. Glasdegib (PF-04449913) binds to human SMO (amino acids 181-787) with an IC50 of 4 nM[1].

IC50 & Target    
IC50: 4 nM (Smo)

体外研究
(In Vitro)    
Glasdegib (PF-04449913) inhibits sonic hedgehog (Shh) stimulated luciferase expression in mouse embryonic fibroblasts with an IC50 of 6.8 nM; and significantly reduces medulloblastoma growth in a Ptch1+/-p53+/- allograft model at doses that decreased murine Shh target gene expression. In stromal co-culture experiments, FACS analysis demonstrates a significant reduction in BC LSC by Glasdegib (PF-04449913) when compared with normal progenitors. Importantly, human BC LSC engrafted RAG2-/-γC-/- mice treated daily with Glasdegib (PF-04449913) compared with vehicle treated controls have a significant spleen weight reduction (p=0.006). This reduction in leukemic burden corresponded with decreased GLI2 protein expression, as determined by both nanoproteomic analysis of FACS purified human progenitors and GLI2 confocal fluorescence microscopic analysis of splenic sections

体内研究
(In Vivo)    
Human BC LSC engrafted RAG2-/-γC-/- mice treated daily with Glasdegib (PF-04449913) compared with vehicle treated controls had a significant spleen weight reduction (p=0.006). When CD34+ cord blood engrafted NSG mice are treated with Glasdegib (PF-04449913), the frequency of human CD45+ cells, progenitors and both myeloid and lymphoid cell fate commitment remained comparable to vehicle treated controls indicating that unlike LSC, normal human HSC cell fate decisions are Hh pathway independent. These results highlight the important niche dependent effects of selective SMO inhibition that induce GLI2 downregulation in a cell type and context specific manner

分子量    
374.44

性状    
Solid

Formula    
C21H22N6O

CAS 号    
1095173-27-5

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
溶解性数据    
In Vitro: 
DMSO : ≥ 83.33 mg/mL (222.55 mM)

* "≥" means soluble, but saturation unknown.

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    2.6707 mL    13.3533 mL    26.7065 mL
5 mM    0.5341 mL    2.6707 mL    5.3413 mL
10 mM    0.2671 mL    1.3353 mL    2.6707 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°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.
请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

Solubility: ≥ 2.08 mg/mL (5.55 mM); Clear solution

2.
请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

Solubility: ≥ 2.08 mg/mL (5.55 mM); Clear solution

3.
请依序添加每种溶剂： 10% DMSO    90% corn oil

Solubility: ≥ 2.08 mg/mL (5.55 mM); Clear solution
 

参考文献	[1]. Sadarangani A, et al. GLI2 inhibition abrogates human leukemia stem cell dormancy. J Transl Med. 2015 Mar 21;13:98.  [Content Brief]

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