Vismodegib (GDC-0449)

For research use only. Not for use in humans.

目录号：S1082 中文名称：维莫德吉

Vismodegib (GDC-0449) Chemical Structure

CAS No. 879085-55-9

Vismodegib (GDC-0449)是一种新型有效的，特异性hedgehog抑制剂，无细胞试验中IC50为3 nM，也会抑制P-gp，IC50为3.0μM。

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10mM (1mL in DMSO)	RMB 1179.52	现货
5mg	RMB 730.63	现货
50mg	RMB 3046.91	现货
200mg	RMB 8763.3	现货
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客户使用Selleck生产的Vismodegib (GDC-0449)发表文献164篇：

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Neuro Oncol, 2022, noac001

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Sci Rep, 2022, 12(1):7

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NPJ Regen Med, 2022, 7(1):3

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Blood, 2021, blood.2020010207

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Adv Sci (Weinh), 2021, 8(14):2100626

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Sci Adv, 2021, 7(46):eabi5790

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Cell Rep, 2021, 37(1):109774

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Int J Mol Sci, 2021, 22(16)8372

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Mol Cancer Res, 2021, molcanres.MCR-21-0257-A.2021

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Sci Rep, 2021, 11(1):19138

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Genes (Basel), 2021, 12(1)E120

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Dev Dyn, 2021, 10.1002/dvdy.436

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Hum Cell, 2021, 10.1007/s13577-021-00639-4

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Hum Cell, 2021, 10.1007/s13577-021-00579-z

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Commun Biol, 2021, 4(1):544

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Cell Death Dis, 2021, 12(2):199

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Nat Commun, 2020, 11(1):5079

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Nucleic Acids Res, 2020, 48(18):10342-10352

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Front Cell Neurosci, 2020, 14:575690

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Int J Mol Sci, 2020, 18;21(8):2825

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Cancer Cell Int, 2020, 19;20:58

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PLoS One, 2020, 29;15(4):e0231762

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Hum Cell, 2020, 10.1007/s13577-020-00425-8

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JCI Insight, 2020,

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J Clin Invest, 2019, 129(12):5151-5162

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Cancers (Basel), 2019, 11(10)

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Cell Death Dis, 2019, 10(12):952

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Endocr Relat Cancer, 2019, 10.1530/ERC-18-0538

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Stem Cell Res Ther, 2019, 10(1):364

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ACS Chem Biol, 2019, 14(3):348-355

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Lab Invest, 2019, 10.1038/s41374-019-0346-2

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Int J Mol Sci, 2019, 20(17)

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Sci Rep, 2019, 9(1):3353

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Sci Rep, 2019, 9(1):19623

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J Biol Chem, 2019, 294(25):9787-9798

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J Biol Chem, 2019, 294(9):3284-3293

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Front Pharmacol, 2019, 10:89

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Front Genet, 2019,

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Toxicol Lett, 2019, 313:30-41

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Oncol Rep, 2019, 41(1):437-446

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Int J Oral Sci, 2019, 11(1):3

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Phytomedicine, 2019, 67:153163

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Nat Cell Biol, 2018, 20(8):909-916

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Nat Commun, 2018, 13;9(1):2720

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Nat Commun, 2018, 9(1):2897

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Sci Signal, 2018, 11(547)eaau5147

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Cell Chem Biol, 2018, 25(4):357-369

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Oncoimmunology, 2018, 8(3):1548241

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Eur J Med Chem, 2018, 156:554-562

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Toxicol Sci, 2018, 166(2):394-408

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Bone Res, 2018, 6:30

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Oncol Lett, 2018, 15(5):6107-6114

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Proc Natl Acad Sci U S A, 2017, 114(44):E9386-E9394

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Cancer Res, 2017, 77(12):3217-3230

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J Control Release, 2017, 261:105-112

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Oncogene, 2017, 36(45):6306-6314

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Oncogene, 2017, 36(32):4641-4652

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Br J Cancer, 2017, 117(9):1314-1325

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Cancer Discov, 2017,

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Sci Rep, 2017, 7(1):3815

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Am J Pathol, 2017, 187(5):1068-1092

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Cancer Chemother Pharmacol, 2017, 79(2):411-420

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Anticancer Drugs, 2017, 28(10):1106-1117

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J Craniofac Surg, 2017, 28(6):1607-1614

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Oncotarget, 2017, 8(61):103744-103757

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Cell Cycle, 2017, 16(14):1357-1365

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Oncotarget, 2017, 8(30):48660-48670

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Oncotarget, 2017,

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Cell Mol Immunol, 2017, 14(2):214-222

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Hepatology, 2016, 63(4):1155-69

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NATURE COMMUNICATIONS, 2016, 10.1038/ncomms10993

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Nat Commun, 2016, 7:11151

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Cancer Res, 2016, 76(18):5538-49

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Cancer Res, 2016, 76(24):7168-7180

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Arthritis Rheumatol, 2016, 68(10):2432-43

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Cell Death Dis, 2016, 7(9):e2376

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Stem Cells, 2016, 34(1):55-66

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PLoS Genet, 2016, 12(9):e1006279

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Oxid Med Cell Longev, 2016, 2016:9826726

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Sci Rep, 2016, 6:24039

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Clin Lung Cancer, 2016, 17(4):301-8

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Mol Med Rep, 2016, 13(2):1434-40

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Oncotarget, 2016, 7(51):84286-84298

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Oncotarget, 2016,

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Sci Rep, 2016, 6:20189

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Clin Cancer Res, 2015, 21(20):4686-97

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PLoS Genet, 2015, 11(6):e1005214

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Development, 2015, 142(19):3374-82

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Am J Cancer Res, 2015, 5(4):1337-52

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Front Oncol, 2015, 5:130

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Sci Rep, 2015, 5:16232

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Sci Rep, 2015, 5:14135

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Mol Carcinog, 2015, 10.1002/mc.22300

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Breast Cancer Res Treat, 2015,

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Cell Cycle, 2015, 14(1):31-45

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Cell Cycle, 2015, 747:71-87

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PLoS One, 2015, 10(3):e0116390

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PLoS One, 2015, 10(10):e0139830

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Biochem Biophys Res Commun, 2015, 457(3):318-23

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Oncol Lett, 2015, 9(6):2675-2679

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Oncotarget, 2015, 6(30):28895-910

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Sci Rep, 2015, 5:7915

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Cell Rep, 2014, 8(5):1405-18

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J Exp Clin Cancer Res, 2014, 33:34

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Mol Pharmacol, 2014, 83(5):1020-9

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Universite Pierre et Marie Curie , 2014, LEPRIEUR EP

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Gut, 2012, 61(9):1323-9

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Hepatology, 2011, 54(5):1580-90

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Mol Cancer, 2011, 10:66

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产品安全说明书

Hedgehog/Smoothened抑制剂选择性比较

生物活性

产品描述

Vismodegib (GDC-0449)是一种新型有效的，特异性hedgehog抑制剂，无细胞试验中IC50为3 nM，也会抑制P-gp，IC50为3.0μM。

靶点

Hedgehog ^[1]
(Cell-free assay)

3 nM

体外研究

GDC-0449有效抑制hedgehog通路，是一种新型及特定合成的小分子抑制剂，IC50为3nM。^[1] GDC-0449作用于Hedgehog信号通路，阻断Hedgehog配位体，即细胞表面受体PTCH 及SMO的活性，从而阻断Hedgehog信号通路。在组织生长和修复方面，Hedgehog信号通路意义重大。Hedgehog通路信号的异常激活，及不受控制的细胞增殖，可能与Hedgehog配位体，即细胞表面受体PTCH 及SMO的突变有关。在体外，GDC-0449在不抑制胰脏细胞增殖的前提下阻止原代胰脏移植物的生长，这项结果最近已经应用到临床。GDC-0449也抑制ABCG2, P-糖蛋白, 及和MDR有关联的重要MRP1 ABC载体。GDC-0449也阻断其他多种ABC载体。ABC载体属于一个膜蛋白家族，它的过量表达和耐药性有关，这也是治疗癌症的一个重大障碍。GDC-0449强抑制两种ABC载体，ABCG2/BCRP和ABCB1/P-糖蛋白，也温和抑制ABCC1/MRP1。在ABCG2过量表达的HEK293细胞中, GDC-0449可以提高荧光ABCG2底物BODIPY-哌唑嗪的保持力，也可用米托蒽醌再次处理这些细胞，产生抗肿瘤的ABCG2底物。实验使Madin-Darby犬的肾脏细胞中过量表达P糖蛋白或者MRP1，GDC-0449 提高了钙黄绿素-AM的保持力，然后载用秋水仙素处理这些细胞。另外，用米托蒽醌,托泊替康,SN-38处理的过量表达ABCG2的人类非小细胞肺癌细胞NCI-H460/par和NCI-H460/MX20，用GDC-0449再次处理。GDC-0449 作用于ABCG2 和 Pgp 的IC50值分别为1.4μM和 3.0 μM。^[2]GDC-0449 改变细胞内Ca²⁺ 平衡，且作用于抗cisplatin的肺癌细胞，抑制细胞生长。^[3]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
IGROV-1	MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MYrJR\|UxRTBwMEeyOFgh\|ryP	NGXkdZM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw1PzN2MUevK\|5USU6JRWK8M4E,
HCE-T	MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MlfUTWM2OD1zLkOyNlQ4KM7:TR?=	NUfMd\|k5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPDd\|NEG3M{c,W0GQR1XSQE9iRg>?
D-542MG	NV\2UpJXT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MmSwTWM2OD1zLki2O\|M4KM7:TR?=	Ml;TQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOFc{PDF5Lze+V2FPT0WUPD;hQi=>
23132-87	NITKZnFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M2izcmlEPTB;ND60NFE1PyEQvF2=	MkLqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOFc{PDF5Lze+V2FPT0WUPD;hQi=>
HDLM-2	MmKzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NX;yd4hUUUN3ME24MlA1PzZ4IN88US=>	MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly0O\|M1OTdxJ{7TRW5ITVJ:L3G+
ACN	NUHiNVZIT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			Mn;aTWM2OD16LkWwNVA6KM7:TR?=	NEPmVoc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw1PzN2MUevK\|5USU6JRWK8M4E,
HuO-3N1	M{HueGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			M{n2TWlEPTB;OT62NFExQCEQvF2=	M3\aZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFQ4OzRzNz:nQnNCVkeHUkyvZV4>
BHT-101	NIe3fFJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NXvSPXVwUUN3ME2xNU4{QCEQvF2=	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly0O\|M1OTdxJ{7TRW5ITVJ:L3G+
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T315I BCR-ABL BaF3	MmG1SpVv[3Srb36gRZN{[Xl?	NVHNdmRrOTBizszN	NFzLcJM4OiCq	NUf4RphQemWmdXPld{B1cGViZYjwdoV{e2mxbjDv[kBIdGlzwrC=	MlPMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN\|MUm4NlQoRjJ\|M{G5PFI1RC:jPh?=
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HEPM	NI\jNIdHfW6ldHnvckBie3OjeR?=			M{PoZmlvcGmkaYTpc44hd2ZiSHXk[4Vpd2dic3nncoFtcW6pIHnuJIh2dWGwIFjFVG0h[2WubIOgZZN{\XO\|ZXSgZZMhemWmdXP0bY9vKGmwIILlZ4VxfG:{LX3l[IlifGWmIFfsbVEhdVKQQTDlfJBz\XO\|aX;uJIJ6KHKncH;yeIVzKGenbnWgZZN{[XluIFnOTEA:KDBwMECzJO69VS5?	NGLQdmk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEi3OVc1OSd-MkC4O\|U4PDF:L3G+
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NIH/3T3	MnG4SpVv[3Srb36gZZN{[Xl?			MmOzTY5pcWKrdHnvckBw\iCqZXTn[Yhw\yC\|aXfuZYxqdmdicHH0bJdigSCrbjDtc5V{\SCQSVivN3Q{KGOnbHzzJIV5eHKnc4Ppcochf2muZDD0fZBmKFOvbzDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5iR3zpJI1TVkFiZYjwdoV{e2mxbjDifUBTXC2SQ2KgcYV1cG:mLDDJR\|UxKD1iMD6wNVQ1KM7:TT6=	NGfDeoM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{ixNFU6OSd-Mke4NVA2QTF:L3G+
S12	MUnGeY5kfGmxbjDhd5NigQ>?		NYrjenlrPDhiaILz	M1j3NWlvcGmkaYTpc44hd2ZiaIXtZY4hW0iKIIDheIh4[XliaX6gcY92e2ViU{GyJINmdGy\|IHHzd4V{e2WmIHHzJGdNUS2vZXTpZZRm\CC2cnHud4NzcXC2aX;uZYwh[WO2aY\peJkh[W[2ZYKgOFghcHK\|IHL5JIx2[2moZYLhd4UhemWyb4L0[ZIh\2WwZTDhd5NigSxiSVO1NEA:KDBwMEG1JO69VS5?	M3XNO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzNEO4OVI4Lz5{MUSzPFUzPzxxYU6=
NIH/3T3	NYLZNXVITnWwY4Tpc44h[XO\|YYm=			NU\jN3hpUW6qaXLpeIlwdiCxZjDTUW8hcW5ibX;1d4UhVkmKL{PUN{Bk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIGPBS{1qdmS3Y3XkJIhm\GenaH;nMY1m\GmjdHXkJIx2dWmwZYPj[Y5k\SC\|aXfuZYxqdmdiYomgS3JGNWy3Y3nm[ZJie2VicnXwc5J1\XJiZ3Xu[UBie3OjeTygTWM2OCB;IECuNFE3KM7:TT6=	MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFzOUWwNEc,OjZzMUm1NFA9N2F-
U2OS	NWqzR41LTnWwY4Tpc44h[XO\|YYm=		NEnCVVkzKGi{cx?=	MYfEbZNxdGGlZX3lcpQhd2ZiW{PIYYN6[2yxcHHtbY5mKG[{b32ge4lt\CC2eYDlJHNudyCneIDy[ZN{\WRiaX6gWVJQWyClZXzsd{Bi\nSncjCyJIhzeyCkeTDzZ4lvfGmubHH0bY9vKGOxdX70bY5oNCCNaTC9JFAvODF4MjFOwG0v	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzB4M{WyNkc,OjNyNkO1NlI9N2F-
NIH3T3	MlXHSpVv[3Srb36gZZN{[Xl?		MlvrN\|AhcHK\|	NX3aeWpHUW6qaXLpeIlwdiCxZjDTcY8hemWlZYD0c5IhMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iTlnIN3Q{KGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gV41wKGGpb37pd5QhW0GJLXnu[JVk\WRiR2LFJIFkfGm4YYTpc44h[W[2ZYKgN\|AhcHK\|IHL5JIx2[2moZYLhd4UhemWyb4L0[ZIh\2WwZTDhd5NigSxiSVO1NEA:KDBwMEKzJO69VS5?	M2LYXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2N{K2PFA4Lz5{NEeyOlgxPzxxYU6=
medulloblastoma cell	MlnuRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		M2TE[lM3KGi{cx?=	NEfPZ\|FCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JHB1[2htLz2gZY5lKHB3Mz2vMUBud3W\|ZTDt[YR2dGyxYnzhd5RwdWFiY3XscJMh[W[2ZYKgN\|YhcHK\|IHL5JGJz\HViaX7jc5Jxd3KjdHnvckBie3OjeTygTWM2OCB;IECuNFMxPCEQvF2u	NIrPeYI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OE[4PFI4QCd-Mki2PFgzPzh:L3G+
Shh Light2	M2DsbGZ2dmO2aX;uJIF{e2G7			NH\rcldCdnSjZ3;ubZN1KGGldHn2bZR6KGG2IIPtc491cGWwZXSgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO\|ZXSgbY4hdW:3c3WgV4hpKEyrZ3j0NkBk\WyuczDjc{1mgHC{ZYPzbY5oKEeuaT3k[ZBmdmSnboSgdoVxd3K2ZYKg[4Vv\SCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKEiqIIPp[45idGmwZzDifUBlfWGuIHz1Z4ln\XKjc3WgdoVxd3K2ZYKg[4Vv\SCjc4PhfUwhUUN3MDC9JFAvODN\|IN88UU4>	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR7MUS1PUc,OjR2OUG0OVk9N2F-
Light2	MkfSSpVv[3Srb36gZZN{[Xl?			MnruTY5pcWKrdHnvckBw\iCqZXTn[Yhw\yC\|aXfuZYxqdmdicHH0bJdigSCrbjDtc5V{\SCOaXfoeFIh[2WubIOgbY4hW2iqIHPvcoRqfGmxbnXkJI1m\Gm3bTDifUBIdGlvbIXjbYZmemG\|ZTDy[ZBwenSncjDn[Y5mKGG\|c3H5MEBKSzVyIE2gNE4xOzlizszNMi=>	MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDh5M{OwN{c,Ojh6N{OzNFM9N2F-
Shh Light2	NWHRNphjTnWwY4Tpc44h[XO\|YYm=			NHPqcnJKdmirYnn0bY9vKG:oIGPtc{1u\WSrYYTl[EBJcCC\|aXfuZYxtcW6pIIDheIh4[XliaX6gcY92e2ViU3joJGxq\2i2MjDj[YxteyCkeTDHcIkudHWlaX\ldoF{\SC{ZYDvdpRmeiCpZX7lJIF{e2G7LDDJR\|UxKD1iMD6wN\|kzKM7:TT6=	MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzd\|NkC2N{c,Ojd5M{[wOlM9N2F-
ASZ001	NWnpTGxbTnWwY4Tpc44h[XO\|YYm=		NHrhXZA1QCCqcoO=	Mlu5TY5pcWKrdHnvckBw\iCKZXTn[Yhw\yC\|aXfuZYxqdmdiaX6gcY92e2ViQWPaNFAyKGOnbHzzJIF{e2W\|c3XkJIF{KGSxd37y[Yd2dGG2aX;uJI9nKEeuaUGgcXJPSSCneIDy[ZN{cW:wIHHmeIVzKDR6IHjyd{BjgSCUVD3QR3Ih[W6jbInzbZMtKEmFNUCgQUAxNjB2IN88UU4>	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyMEexOkc,OjR7MEC3NVY9N2F-
NIH/3T3	NX\EeJFITnWwY4Tpc44h[XO\|YYm=		M1zPOVQ5KGi{cx?=	Mnu1RY51[WexbnnzeEBi[3Srdnn0fUBifCCVbX:gdoVk\XC2b4KgbY4hdW:3c3WgUmlJNzOWMzDj[YxteyCqYYLic5JqdmdiR2LFMWx2[yCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKFODRz3pcoR2[2WmIFjoJJNq\26jbHnu[{Bx[XSqd3H5JJBz\WmwY4XiZZRm\CC5aYToJINmdGy\|IH\vcIxwf2WmIHL5JHNCTyCjZHTpeIlwdiCvZXHzeZJm\CCjZoTldkA1QCCqcoOgZpkhdHWlaX\ldoF{\SC{ZYDvdpRmeiCpZX7lJIF{e2G7LDDJR\|UxKD1iMD6wOFYh\|ryPLh?=	MoS1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl6NUeyO\|UoRjJ7OEW3Nlc2RC:jPh?=
Light2	Mk[0SpVv[3Srb36gZZN{[Xl?		M2TXW\|MxKGi{cx?=	MmnwTY5pcWKrdHnvckBw\iCqZXTn[Yhw\yC\|aXfuZYxqdmdicHH0bJdigSCrbjDtc5V{\SCOaXfoeFIh[2WubIOgbY4hW2iqIHPvcoRqfGmxbnXkJI1m\Gm3bTDh[pRmeiB\|MDDodpMh[nliR3zpMXJmdmmubHGgcJVkcW[ncnHz[UBz\XCxcoTldkBo\W6nIHHzd4F6NCCLQ{WwJF0hOC5yNTFOwG0v	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODB7OUK1O{c,OzByOUmyOVc9N2F-
C3H10T1/2	NGXqOlRHfW6ldHnvckBie3OjeR?=		NH\Ne3M3KGSjeYO=	NVLhO\|NkUW6qaXLpeIlwdiCxZjDo[YRo\WixZzDzbYdv[WyrbnegdIF1cHejeT3t[YRq[XSnZDDkbYZn\XKnboTpZZRqd25ib3[gcY92e2ViQ{PINVBVOS9{IHPlcIx{KGG\|c3Xzd4VlKGG\|IHTlZ5Jm[XOnIHnuJHNCTy2rbnT1Z4VlKEGOUDDhZ5Rqfmm2eTDh[pRmeiB4IHThfZMh[nliY3jlcYltfW2rbnXzZ4Vv[2VvYnHz[YQh[XO\|YYmsJGlEPTBiPTCwMlA2KM7:TT6=	M12yTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMEm5NlU4Lz5\|MEC5PVI2PzxxYU6=
DaOY	M2PEOmZ2dmO2aX;uJIF{e2G7		NV\DZVFxPDhiaILz	NHzJeZhKdmirYnn0bY9vKG:oIFjl[IdmcG:pIIPp[45idGmwZzDpckBpfW2jbjDEZW9[KGOnbHzzJIF{e2W\|c3XkJIF{KGSxd37y[Yd2dGG2aX;uJI9nKEeuaUGgcXJPSSCneIDy[ZN{cW:wIHHmeIVzKDR6IHjyd{BjgSCUVD3QR3Ih[W6jbInzbZMtKEmFNUCgQUAxNjB6NjFOwG0v	NXXEdlBDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFA4OTZpPkK0PVAxPzF4PD;hQi=>
C3H10T1/2	MkTlSpVv[3Srb36gZZN{[Xl?		MUCxJIhz	M3SxSWlvcGmkaYTpc44hd2ZiSHXk[4Vpd2dic3nncoFtcW6pIIDheIh4[XliaX6gcY92e2ViQ{PINVBVOS9{IHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDpckBxfXKvb4LwbIFucW6nLXnu[JVk\WRiaX7jdoVie2ViaX6gZYxs[WyrbnWgdIhwe3CqYYThd4UhdGW4ZXygeZNqdmdiQ1TQMZN1[XJiYYOgd5Vje3S{YYTlJJBz\XS{ZXH0[YQh\m:{IEGgbJIh\m:ubH;3[YQh[nlicIXycY9zeGijbXnu[UBi\GSrdHnvckBu\WG\|dYLl[EBi\nSncjC1JIRigSxiSVO1NEA:KDBwMUSg{txONg>?	MorBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh7NEe5N\|koRjJ6OUS3PVM6RC:jPh?=
M210B4	MkPzSpVv[3Srb36gZZN{[Xl?		NH[4dHozPCCqcoO=	Mne5TY5pcWKrdHnvckBw\iCKZXTn[Yhw\yC\|aXfuZYxqdmdiaX6gcY92e2ViTUKxNGI1KGOnbHzzJIF{e2W\|c3XkJIF{KGSxd37y[Yd2dGG2aX;uJI9nKFC2Y3igcXJPSSCneIDy[ZN{cW:wIHHmeIVzKDJ2IHjyd{BjgSCUVD3QR3Ih[W6jbInzbZMtKEmFNUCgQUAxNjF2IN88UU4>	M{LOU\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUCwO\|E3Lz5{NEmwNFcyPjxxYU6=
M210B4	MXPGeY5kfGmxbjDhd5NigQ>?		NWKxPYNVOjRiaILz	NF\3NJdKdmirYnn0bY9vKG:oIFjl[IdmcG:pIIPp[45idGmwZzDpckBud3W\|ZTDNNlExSjRiY3XscJMh[XO\|ZYPz[YQh[XNiZH;3cpJm\3WuYYTpc44hd2ZiR3zpNUBuWk6DIHX4dJJme3Orb36gZYZ1\XJiMkSgbJJ{KGK7IGLUMXBEWiCjbnHsfZNqeyxiSVO1NEA:KDBwMjFOwG0v	MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyMEexOkc,OjR7MEC3NVY9N2F-
Shh Light2	MnjvSpVv[3Srb36gZZN{[Xl?		MkmyNUBpeg>?	NIXMVopKdmirYnn0bY9vKG:oIFjl[IdmcG:pIIPp[45idGmwZzDpckBud3W\|ZTDTbIghVGmpaISyJINmdGy\|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiCydYLtc5JxcGGvaX7lMYlv\HWlZXSgS4xqKG2nZHnheIVlKHS{YX7zZ5JqeHSrb37hcEBi[3Srdnn0fUBxemW2cnXheIVlKG[xcjCxJIhzKG[xbHzve4VlKGK7IID1do1wenCqYX3pcoUh[WSmaYTpc44hdWWjc4Xy[YQh[W[2ZYKgOFghcHK\|IHL5JIx2[2moZYLhd4UhemWyb4L0[ZIh\2WwZTDhd5NigSxiSVO1NEA:KDBwOUig{txONg>?	MnHzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh7NEe5N\|koRjJ6OUS3PVM6RC:jPh?=
NIH/3T3	NUTTW2tITnWwY4Tpc44h[XO\|YYm=			NHTsOXpKdmirYnn0bY9vKG:oIHjl[IdmcG:pIIPp[45idGmwZzDwZZRpf2G7IHnuJI1wfXOnIF7JTE8{XDNiY3XscJMhcGG{Yn;ybY5oKFOvbzDEOFc4UCCvdYThcpQh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJGdtcSCvUl7BJIV5eHKnc4Ppc44h[nliUmStVGNTKG2ndHjv[EwhUUN3MDC9JFEvOTl4IN88UU4>	M2jZdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5OEGwOVkyLz5{N{ixNFU6OTxxYU6=
S12	Ml35SpVv[3Srb36gZZN{[Xl?		NYfqSG9pPDhiaILz	MnXiTY5pcWKrdHnvckBw\iCqdX3hckBUUEhicHH0bJdigSCrbjDtc5V{\SCVMUKgZ4VtdHNiYYPz[ZN{\WRiYYOgS2xKNW2nZHnheIVlKHS{YX7zZ5JqeHSrb37hcEBi[3Srdnn0fUBi\nSncjC0PEBpenNiYomgcJVkcW[ncnHz[UBz\XCxcoTldkBo\W6nIHHzd4F6KGmwIIDy[ZNmdmOnIH;mJFAvPSCvZz;tUEBpfW2jbjDhcJBp[S1zLXHjbYQh\2y7Y3;wdo91\WmwLDDJR\|UxKD1iMT63OUDPxE1w	NH7jWpU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUSzPFUzPyd-MkG0N\|g2Ojd:L3G+
Calu6	NWn0WGM6TnWwY4Tpc44h[XO\|YYm=		M4XY[VQhcHK\|	NFvlbWJRdGG\|bXGgZ49v[2WwdILheIlwdiCrbjDoeY1idiCFYXz1OkBk\WyuczD4[Y5w\3KjZoTl[EBqdiCwdXTlJI1wfXOnIHH0JFc2KG2pL3vnMEBxdyCkaXSgcYVie3W{ZXSgZYZ1\XJiNDDodpMheG:\|dDDmbYZ1cCCmb4PlMEBEeCB;IEKzJO69VS5?	NIjKZnc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUexOlI6Pid-MUm3NVYzQTZ:L3G+
Calu-6	NFrlUHVHfW6ldHnvckBie3OjeR?=			MUPQcIF{dWFiY3;uZ4VvfHKjdHnvckBqdiCFYXz1MVYh[2WubIOgfIVvd2e{YX\0[YQhdnWmZTDtc5V{\SCSSz;QSEBud2SnbDDheEA4PSCvZz;r[{wheG9iYnnkJIZweiB3IHThfZMhdWWjc4Xy[YQhPCCqcoOgdI9{fCCuYYP0JIRwe2VicnXsZZRqfmVidH:geY51emWjdHXkJINwdnS{b3ysJGNxKD1iMkOg{txONg>?	NG\xW489[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEi3OVc1OSd-MkC4O\|U4PDF:L3G+
T47D	MYXDfZRwfG:6aXPpeJkh[XO\|YYm=		MV:3NkBpenN?	MoHnR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gWFQ4TCClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG\|c3H5MEBKSzVyIE2gOFEvOzRizszNMi=>	NEezepA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUGwO\|QzQSd-MkmxNFc1Ojl:L3G+
LS180	NGjVZYZCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		M{jNVVczKGi{cx?=	NXzPUm9SSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDMV\|E5OCClZXzsd{Bi\nSncjC3NkBpenNiYomgd5Vt\m:{aH;kZY1qdmVvQjDhd5NigSxiSVO1NEA:KDR3IN88UU4>	Mn;BQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzByOUmyOVcoRjNyMEm5NlU4RC:jPh?=
LS174T	M3nLPWFvfGmycn;sbYZmemG2aY\lJIF{e2G7		M4LrN\|czKGi{cx?=	MYLBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEyVMUe0WEBk\WyuczDh[pRmeiB5MjDodpMh[nliQ3XscHRqfGW{LVfsc{BtfW2rbnXzZ4VvfCClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OCB;IES1MlgyKM7:TT6=	MnfXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ6MkC1OVQoRjJ4OEKwOVU1RC:jPh?=
BxPC3	M4\RPWFvfGmycn;sbYZmemG2aY\lJIF{e2G7		MUO3NkBpenN?	NWOzZ412SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDCfHBEOyClZXzsd{Bi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCudX3pcoV{[2WwdDDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3MDC9JFQ4Njl3IN88UU4>	M3i3NVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4OEKwOVU1Lz5{NkiyNFU2PDxxYU6=
medulloblastoma cell	NEX1VnpCdnSrdIXtc5Ih[XO\|YYm=			MUTBcpRqfHWvb4KgZYN1cX[rdImgZYdicW6\|dDDtc5V{\SCvZXT1cIxw[myjc4TvcYEh[2WubIOgfIVvd2e{YX\0[YQhcW5iUITjbEAsNy1ibX;1d4Uh[XO\|ZYPz[YQh[XNiZHXjdoVie2ViaX6geJVud3Jidn;seY1mKGG2IEGyMlUhdWdxa3esJJBwKGKrZD6=	M1HG[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7N{G2Nlk3Lz5zOUexOlI6PjxxYU6=
S12	NGj5TmtHfW6ldHnvckBie3OjeR?=		MXG0PEBpenN?	MmXDTY5pcWKrdHnvckBw\iCqdX3hckBUUEhicHH0bJdigSCrbjDtc5V{\SCVMUKgZ4VtdHNiYYPz[ZN{\WRiYYOgS2xKNW2nZHnheIVlKHS{YX7zZ5JqeHSrb37hcEBi[3Srdnn0fUBi\nSncjC0PEBpenNiYomgcJVkcW[ncnHz[UBz\XCxcoTldkBo\W6nIHHzd4F6KGmwIIDy[ZNmdmOnIH;mJFEhdWdxbVygbJVu[W5iYXzwbIEuOS2jY3nkJIdtgWOxcILveIVqdi5?	NI\YPYo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUSzPFUzPyd-MkG0N\|g2Ojd:L3G+
Shh Light2	NXjKe2lETnWwY4Tpc44h[XO\|YYm=	MlrENE4yKHWP	MVuzOkBpenN?	NFjNdG9KdmirYnn0bY9vKG:oIGPtc{1u\WSrYYTl[EBJcCC\|aXfuZYxtcW6pIIDheIh4[XliaX6gcY92e2ViU3joJGxq\2i2MjDj[YxteyCjc4Pld5Nm\CCjczDzeZBxemW\|c3nvckBw\iCJbHmxMY1TVkFiZYjwdoV{e2mxbjDheEAxNjFidV2gcYVie3W{ZXSgZYZ1\XJiM{[gbJJ{KGK7IGLUMZFRS1JiYX7hcJl{cXNw	NYnpeVFbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMke3N\|YxPjNpPkK3O\|M3ODZ\|PD;hQi=>
SW1353	NV3peWFVSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=	MmPRNVAhfU1?	MXG0PEBpenN?	NET5[YFCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGPXNVM2OyClZXzsd{Bie3Onc4Pl[EBieyCpcn;3eIghcW6qaXLpeIlwdiCjdDCxNEB2VSCjZoTldkA1QCCqcoOgZpkhVVSWIHHzd4F6Ng>?	MoruQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2OUG0OVkoRjJ2NEmxOFU6RC:jPh?=
DaOY	M1OzfmFvfGmycn;sbYZmemG2aY\lJIF{e2G7	NIXiNZUyOCC3TR?=	NYPP[Iw3PDhiaILz	M3nndWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iRHHPXUBk\WyuczDhd5Nme3OnZDDhd{Boem:5dHigbY5pcWKrdHnvckBifCBzMDD1UUBi\nSncjC0PEBpenNiYomgUXRVKGG\|c3H5Mi=>	M1jPbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NEmxOFU6Lz5{NES5NVQ2QTxxYU6=
A549	MnjJRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?	NHPFRXIyOCC3TR?=	NVHDOYZlPDhiaILz	NF\yS2lCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFG1OFkh[2WubIOgZZN{\XO\|ZXSgZZMh\3Kxd4ToJIlvcGmkaYTpc44h[XRiMUCgeW0h[W[2ZYKgOFghcHK\|IHL5JG1VXCCjc4PhfU4>	Mmr3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2OUG0OVkoRjJ2NEmxOFU6RC:jPh?=
HCT116	M3nVOWFvfGmycn;sbYZmemG2aY\lJIF{e2G7	M2XmV\|ExKHWP	MVW0PEBpenN?	M{jhUmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFPUNVE3KGOnbHzzJIF{e2W\|c3XkJIF{KGe{b4f0bEBqdmirYnn0bY9vKGG2IEGwJJVOKGGodHXyJFQ5KGi{czDifUBOXFRiYYPzZZkv	M1\D[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NEmxOFU6Lz5{NES5NVQ2QTxxYU6=
NIH/3T3	MmjLSpVv[3Srb36gZZN{[Xl?	NHz4SIQyOCC3TR?=		M4LyW2lvcGmkaYTpc44hd2ZiSHXk[4Vpd2dic3nncoFtcW6pIHnuJI1wfXOnIF7JTE8{XDNiY3XscJMh[XO\|ZYPz[YQh[XNiZH;3ckBz\We3bHH0bY9vKG:oIH3QWGNJOSCvUl7BJIV5eHKnc4Ppc44h[XRiMUCgeW0v	NHXGOYY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES5NVQ2QSd-MkS0PVE1PTl:L3G+
MSC	Mnm1SpVv[3Srb36gZZN{[Xl?	NGPhfo4zOCC2bzC4NEB2VQ>?		NHHnendKdmirYnn0bY9vKG:oIHjl[IdmcG:pIIPp[45idGmwZzDpckBud3W\|ZTDNV2Mh[2WubIOgZZN{\XO\|ZXSgZZMh\G:5bjDy[Yd2dGG2aX;uJI9nKGGua3HsbY5mKHCqb4PwbIF1[XOnIHH0JFIxKHSxIEiwJJVONg>?	NGD3cJc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES5NVQ2QSd-MkS0PVE1PTl:L3G+
SK-N-MC	NWDDU4JSeUiWUzDhd5NigQ>?			NUnrTHB2eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPLMW4uVUNiY3XscJMv	M2n0RVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
TC32	NEnTc4hyUFSVIHHzd4F6			MoLBdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgWGM{OiClZXzsd{4>	MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
NIH3T3-Luc	NXvmbJdqTnWwY4Tpc44h[XO\|YYm=	MWKxJJVO	MmPSOFghcHK\|	M3\aOmlvcGmkaYTpc44hd2Zic33vMY1m\GmjdHXkJIhm\GenaH;nJJNq\26jbHnu[{Bx[XSqd3H5JIlvKG2xdYPlJG5KUDOWMz3MeYMh[2WubIOgZZN{\XO\|ZXSgZZMh\G:5boLl[5Vt[XSrb36gc4YhT2yrIH3SUmEh\XiycnXzd4lwdiCjdDCxJJVOKGGodHXyJFQ5KGi{czDifUBz\WGuLYTpcYUhWEOUIHHuZYx6e2m\|Lh?=	MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR7OUS4N{c,Ojl2OUm0PFM9N2F-
C3H10T1/2	MUPGeY5kfGmxbjDhd5NigQ>?		NEjkNpEzPCCqcoO=	MVXJcohq[mm2aX;uJI9nKGinZHflbI9oKHOrZ37hcIlv\yCyYYToe4F6NW2nZHnheIVlKEeOSUGgcXJPSSCneIDy[ZN{cW:wIHnuJI1wfXOnIFOzTFExXDFxMjDj[YxteyCjZoTldkAzPCCqcoOgZpkhWlRvUFPSJIFv[Wy7c3nzJIlvKHC{ZYPlcoNmKG:oIDixVkw{[VJuNGOsO4FTMS15YT3t[ZRpgWxvMT2oLHIqNTZvbXX0bJltcGWydHHuMVIugWxrb3P0ZYh6\HKxLUHIMYlv\GWwLUStfYwhOy2qeXTyc5h6[mWwen;heIUv	NUW2ZmxZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS3N\|A6QDRpPkK0O\|MxQTh2PD;hQi=>
C3H10T1/2	MWDGeY5kfGmxbjDhd5NigQ>?		MUKyOEBpenN?	NVL3fmN7UW6qaXLpeIlwdiCxZjDo[YRo\WixZzDzbYdv[WyrbnegdIF1cHejeT3t[YRq[XSnZDDHUGkyKG2UTlGg[ZhxemW\|c3nvckBqdiCvb4Xz[UBEO0hzMGSxM\|Ih[2WubIOgZYZ1\XJiMkSgbJJ{KGK7IGLUMXBEWiCjbnHsfZNqeyCrbjDwdoV{\W6lZTDv[kBXTDNw	MlzkQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR5M{C5PFQoRjJ2N{OwPVg1RC:jPh?=
NIH/3T3	MWXGeY5kfGmxbjDhd5NigQ>?	NUflR2dnOTByIH7N	M13WT\|M3KGi{cx?=	M{LSNGlvcGmkaYTpc44hd2ZiaHXk[4Vpd2dic3nncoFtcW6pIIDheIh4[XliaX6gcY92e2ViTlnIM\|NVOyClZXzsd{Bie3Onc4Pl[EBieyCmb4fudoVofWyjdHnvckBw\iCVaHitbY5lfWOnZDDHcIkyKG2UTlGg[ZhxemW\|c3nvckBt\X[nbIOgZZQhOTByIH7NJIFnfGW{IEO2JIhzeyCkeTDSWE1yWEOUIHHuZYx6e2m\|Lh?=	NVPxW2dURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki4O\|M{ODNpPkK4PFc{OzB\|PD;hQi=>
C3H10T1/2	MoLzSpVv[3Srb36gZZN{[Xl?	M2X6R\|ExOCCwTR?=	Mlj3N\|YhcHK\|	NFK4NGdKdmirYnn0bY9vKG:oIHjl[IdmcG:pIIPp[45idGmwZzDwZZRpf2G7IHnuJI1wfXOnIFOzTFExXDFxMjDj[YxteyCjc4Pld5Nm\CCjczDkc5dvemWpdXzheIlwdiCxZjDTbIgucW6mdXPl[EBIdGlzIH3SUmEh\XiycnXzd4lwdiCuZY\lcJMh[XRiMUCwJI5OKGGodHXyJFM3KGi{czDifUBTXC2zUFPSJIFv[Wy7c3nzMi=>	M2PweVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6OEezN\|A{Lz5{OEi3N\|MxOzxxYU6=
NIH/3T3	NHf0TJlHfW6ldHnvckBie3OjeR?=	NYLHTnBCOTByIH7N	MUizOkBpenN?	NUfTfpJPUW6qaXLpeIlwdiCxZjDo[YRo\WixZzDzbYdv[WyrbnegdIF1cHejeTDpckBud3W\|ZTDOTWgwO1R\|IHPlcIx{KGG\|c3Xzd4VlKGG\|IHTve45z\We3bHH0bY9vKG:oIGPobE1qdmS3Y3XkJJB1[2hzIH3SUmEh\XiycnXzd4lwdiCuZY\lcJMh[XRiMUCwJI5OKGGodHXyJFM3KGi{czDifUBTXC2zUFPSJIFv[Wy7c3nzMi=>	M{nrPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6OEezN\|A{Lz5{OEi3N\|MxOzxxYU6=
C3H10T1/2	M1;xZ2Z2dmO2aX;uJIF{e2G7	MVWxNFAhdk1?	M{TtSVM3KGi{cx?=	MUnJcohq[mm2aX;uJI9nKGinZHflbI9oKHOrZ37hcIlv\yCyYYToe4F6KGmwIH3veZNmKEN\|SEGwWFEwOiClZXzsd{Bie3Onc4Pl[EBieyCmb4fudoVofWyjdHnvckBw\iCVaHitbY5lfWOnZDDweINpOSCvUl7BJIV5eHKnc4Ppc44hdGW4ZXzzJIF1KDFyMDDuUUBi\nSncjCzOkBpenNiYomgVnQueVCFUjDhcoFtgXOrcz6=	NU\rUo52RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki4O\|M{ODNpPkK4PFc{OzB\|PD;hQi=>
medulloblastoma cell	MmXVRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?	MoG2eZAhfG9iM{CgeW0>	NXLITpR5PzJiaILz	NETLS3BCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JI1wfXOnIGD0Z4gsNy1icEWzMU8uKG2nZIXscI9jdGG\|dH;tZUBk\WyuczDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5iY3XscEBxem:uaX\ldoF1cW:wIIXwJJRwKDNyIIXNJIFnfGW{IEeyJIhzeyCkeTDNWHMh[XO\|YYmu	NWfh[YNQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki4O\|M{ODNpPkK4PFc{OzB\|PD;hQi=>
medulloblastoma cell	MX;BdI9xfG:\|aYOgZZN{[Xl?			MX\JcoR2[3Srb36gc4Yh[XCxcITvd4l{KGmwIH3veZNmKFC2Y3irM{0heDV\|LT:tJI1m\HWubH;icIF{fG:vYTDj[YxteyCrbYDsZY51\WRiaX6gZZRpgW2rYzDueYRmKG2xdYPlJIF1KDF{LkWgcYcwc2duIHnwJIJq\CCob4KgNVUh[2:wc3XjeZRqfmViZHH5d{BjgSCWVV7FUEBie3OjeT6=	MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDh5M{OwN{c,Ojh6N{OzNFM9N2F-
NIH/3T3	MUDGeY5kfGmxbjDhd5NigQ>?			NIHj[phKdmirYnn0bY9vKG:oIHjl[IdmcG:pIIPp[45idGmwZzDwZZRpf2G7IHX4dJJme3OnZDDpckBud3W\|ZTDOTWgwO1R\|IHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhcGWmZ3Xoc4cucW6mdXPl[EBIdGlvMjDhZ4N2dXWuYYTpc44h[XRidHnwJI9nKHC{aX3hdpkh[2muaXGgZpkhTEGSSTDzeIFqdmmwZzDiZZNm\CClb37mc4NidCCvaXPyc5Nkd3CrYzDhcoFtgXOrcz6=	NGrIcG89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{ixNFU6OSd-Mke4NVA2QTF:L3G+
NIH/3T3	MXTGeY5kfGmxbjDhd5NigQ>?			NHrqPXFKdmirYnn0bY9vKG:oIHjl[IdmcG:pIIPp[45idGmwZzDwZZRpf2G7IHnuJI1wfXOnIF7JTE8{XDNiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBp\WSpZXjv[{1qdmS3Y3XkJHNudy2HR1\QJINqdGmjcomgeJJidnOub3PheIlwdiCkeTDERXBKKHO2YXnubY5oKGKjc3XkJINwdm[xY3HsJI1q[3Kxc3PvdIlkKGGwYXz5d4l{Ng>?	M4ThRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5OEGwOVkyLz5{N{ixNFU6OTxxYU6=
medulloblastoma cell	NFPwbVFCdnSrLYT1cY9zKGG\|c3H5			NV;qd5FTSW62aT30eY1weiCjY4Tpeol1gSCjZ3HpcpN1KG2xdYPlJHB1[2htLz2gdFU{NS9vIH3l[JVtdG:kbHHzeI9u[SClZXzsd{BqdXCuYX70[YQhcW5iYYTofY1q[yCwdXTlJI1wfXOnIHHzd4V{e2WmIHHzJJR2dW:{IHfyc5d1cCCrbnjpZol1cW:wIHH0JFIxKG2pL3vnMEBxdyCjZH3pcol{fGW{ZXSgeJdq[2ViZHHpcJkhfmmjIHfheoFo\SCvZXHzeZJm\CCndnXyfUBwfGincjDkZZkh\HW{aX7nJINwdXCxdX7kJIRwe2mwZz6=	NIixXZQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUezPVcyPCd-Mkm3N\|k4OTR:L3G+
C3H10T1/2	M1W4RmZ2dmO2aX;uJIF{e2G7	MWG0MlEhfG9iMUCwNEBvVQ>?		NV7pZWFRSWyub4P0[ZJq[yCrbnjpZol1cW:wIH;mJHNudyCrbjDtc5V{\SCFM1ixNHQyNzJiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBxfXKvb4LwbIFucW6nLXnu[JVk\WRiR3zpNUB1emGwc3PybZB1cW:wYXygZYN1cX[rdImgZZQhPC5zIITvJFExODBibl2gZpkheVCFcjDhcoFtgXOrcz6=	M3e1OVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|MEe0OVQyLz5{M{C3OFU1OTxxYU6=
C3H10T1/2	M4HseWZ2dmO2aX;uJIF{e2G7	MkHqOE4yKHSxIEGwNFAhdk1?		NF7jbWtEd22yZYTpeIl3\SCrbnjpZol1cW:wIH;mJHNudyCrbjDtc5V{\SCFM1ixNHQyNzJiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBUSUdvaX7keYNm\CCJbHmxJJRz[W6\|Y4LpdJRqd26jbDDhZ5Rqfmm2eTDheEA1NjFidH:gNVAxOCCwTTDifUByWEOUIHHuZYx6e2m\|Lh?=	NFLPeFU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{C3OFU1OSd-MkOwO\|Q2PDF:L3G+

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Assay

Methods	Test Index	PMID
Western blot	Bcl-2 / Bax; PubMed: 28195165 Sci Rep GDC-0449 treatment affected the expression levels of cell cycle-related protein levels. U251 cells were treated with 0.1% DMSO or GDC-0449 at the indicated concentrations for 24 h. Cells were then harvested and examined using Western blot analysis with the indicated antibodies. p53 / Cyclin D1 / p21; PubMed: 28195165 Sci Rep GDC-0449 treatment affected the expression levels of cell cycle-related protein levels. U251 cells were treated with 0.1% DMSO or GDC-0449 at the indicated concentrations for 24 h. Cells were then harvested and examined using Western blot analysis with the indicated antibodies. Gli1 / SOX2 / OCT4; PubMed: 26418365 Stem Cells The activation of Hedgehog pathways and CSC markers were tested by immunoblotting analysis in Hs578T and BT549 cells. β‐Actin was used as a loading control. p-GSK3β / GSK3β / p-Akt / Akt / Gli1; PubMed: 27143997 Oxid Med Cell Longev Cells were pretreated with or without 30 μM GDC-0449 for 2 h before TMT treatment. After incubation with 3.75 μM TMT for another 24 h, the expression levels of proteins were determined through Western blot analysis. Fas / DR4 / DR5 / Cleaved PARP / Bcl-2 / Cleaved caspase-3 / PDGFRα; PubMed: 22087285 PLoS One Pancreatic CSCs were treated with GDC-0449 (0, 1, 5 and 10 µM) for 48 h. The expression of Fas, DR4/TRAIL-R1, DR5/TRAIL-R2, PARP cleavage, Bcl-2, and Caspase-3 by the Western blot analysis. β-Actin was used as a loading control.	28195165 26418365 27143997 22087285
Immunofluorescence	Gli1 / Gli2; PubMed: 22087285 PLoS One GDC-0449 inhibits expression of Gli1 and Gli2 in human pancreatic CSCs. The cells were seeded on fibronectin-coated coverslips and treated with GDC-0449 (10 µM) for 48 h. Subsequently, cells were fixed with 4% paraformaldehyde, blocked in 10% normal goat serum and stained with Gli1 and Gli2 primary antibodies (1∶100) for 16 h at 4°C and washed with PBS. Afterwards, cells were incubated with fluorescently labeled secondary antibody (1∶200) along with DAPI (1 mg/ml) for 1 h at room temperature and cells were mounted and visualized under a fluorescent microscope. For better visuality, the color of DAPI was changed from blue to red.	22087285
Growth inhibition assay	Cell viability; PubMed: 29042665 Sci Rep GDC-0449 improves the anti-proliferation activity in NIH-3T3 cells but not in BxPC-3, Panc-1, MIAPaca-2 and SW1990 cells when cultured alone. The cytotoxicities of GDC-0449, Dox or Dox with GDC-0449 (5 μM or 10 μM) were measured by performing a 48-h MTT assay in BxPC-3 (A), Panc-1 (B), MIAPaca-2 (C), SW1990 (D) and NIH-3T3 (E) cells. Apoptosis rate was detected by flow cytometry (Annexin V staining) analysis after treatment with Dox (200 nM) with or without GDC-0449 for 24 h (F). Data are presented as the mean ± SD. P < 0.05, *P < 0.01.	29042665

体内研究

GDC-0449已经用于治疗动物模型的成髓细胞瘤。^[2] GDC-0449 抑制原代胰腺移植瘤生长，但是不抑制细胞增殖。GDC-0449按25 mg/kg 以上剂量口服给药髓母细胞瘤Ptch(+/-)异体移植物模型，引起细胞衰退，按92 mg/kg剂量处理两种配位体依赖的结肠直肠癌模型D5123和1040830，每天处理两次，抑制肿瘤生长。分析Hh通路活性和 PK/PD 模型显示GDC-0449抑制 Gli1，IC50值与GDC-0449作用于髓母细胞瘤和D5123模型的IC50值差不多(分别为0.165 μM ±11.5% 和0.267 μM ±4.83%)。^[4]

细胞实验：^[2]	- 合并 Cell lines: MDCKII细胞 Concentrations: 20 μM Incubation Time: 2小时 Method: MDCKII细胞按每孔3x10⁵密度接种在24孔板中。培养液包含不同药物，实验组为50 µM VP,50 µM吲哚美辛,或者20 µM GDC-0449溶解在DMSO中，对照组只含有DMSO。然后加入非荧光的钙黄绿素-AM，最终浓度达到1.0 µM。然后在37^oC温育2小时。细胞用含Ca²⁺,Mg²⁺的Hank's平衡盐溶液buffer冲洗2次，然后震荡1小时溶解在含0.01% Triton X-100的磷酸缓冲液中，然后放在4^oC下过夜。溶解的物质然后转移到96孔板上，钙黄绿素引起的荧光信号用分光光度法定量。所有的实验操作需在暗中进行，所有的读数用平均值±SEM表示。 (Only for Reference)
动物实验：^[4]	- 合并 Animal Models: Ptch(+/-)异体移植物模型 Dosages: 25 mg/kg,92 mg/kg Administration: 口服 (Only for Reference)

参考文献

[4] Wong H, et al. Clin Cancer Res. 2011, 17(14), 4682-4692.

- 合并

溶解度 (25°C)

体外	DMSO	84 mg/mL (199.38 mM)
	Water	Insoluble
	Ethanol	Insoluble
体内	从左到右依次将纯溶剂加入产品，现配现用(数据来自Selleck实验检测而非文献)： 5% DMSO+40% PEG 300+5% Tween 80+50% ddH2O	12.5mg/mL

* 溶解度检测是由Selleck技术部门检测的，可能会和文献中提供的溶解度有所差异，这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据 Download Vismodegib (GDC-0449) SDF

分子量	421.3
化学式	C₁₉H₁₄Cl₂N₂O₃S
CAS号	879085-55-9
储存条件	3年-20°C 粉状 2年-80°C 溶于溶剂
别名	N/A

动物体内配方计算器 (澄清溶液)

第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）

给药剂量

mg/kg

动物平均体重

每只动物给药体积

动物数量

只

第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）

% DMSO+ % + % Tween 80+ % ddH₂O

计算重置

计算结果:

工作液浓度： mg/ml；

DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；

体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH₂O，混匀澄清。

注意：1. 首先保证母液是澄清的；
2. 一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。

计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

质量

浓度

体积

分子量
=

×

×

*在配置溶液时，请务必参考Selleck产品标签上、SDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。

稀释计算器

用本工具协助配置特定浓度的溶液，使用的计算公式为：

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入输出 )

C1

V1

C2

V2
×

=

×

在配置溶液时，请务必参考Selleck产品标签上、SDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。.

连续稀释计算器方程

连续稀释
初始浓度:
稀释倍数:

计算结果

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

分子量计算器

通过输入化合物的化学式来计算其分子量：

注：化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量	浓度	体积	分子量
=	×	×
计算

临床试验信息 (data from https://clinicaltrials.gov, updated on 2022-01-17)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03610022	Recruiting	Drug: Treatment with vismodegib	Metastatic Basal Cell Carcinoma\|Locally Advanced Basal Cell Carcinoma	University Hospital Bordeaux	September 3 2018	Phase 4
NCT03035188	Unknown status	Drug: Vismodegib	Basal Cell Carcinoma	SRH Wald-Klinikum Gera GmbH	January 2017	Phase 2
NCT02781389	Completed	--	Basal Cell Carcinoma	University Hospital Essen\|OnkoDataMed GmbH	April 29 2016	--
NCT02593760	Completed	Other: Placebo\|Drug: Ruxolitinib\|Drug: Vismodegib	Myelofibrosis	Hoffmann-La Roche	January 25 2016	Phase 1
NCT02648048	Completed	Drug: Pirfenidone\|Drug: Vismodegib	Idiopathic Pulmonary Fibrosis	Hoffmann-La Roche	January 15 2016	Phase 1
NCT02436408	Completed	Drug: Vismodegib	Carcinoma Basal Cell	University of Michigan Rogel Cancer Center	July 15 2015	Phase 4

技术支持

在订购、运输、储存和使用我们的产品的任何阶段，您遇到的任何问题，均可以通过拨打我们的热线电话400-668-6834，或者技术支持邮箱tech@selleck.cn，直接联系到我们。我们会在24小时内尽快联系您。

操作手册

如果有其他问题，请给我们留言。

Hedgehog/Smoothened Signaling Pathway Map

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用于临床的Smoothened抑制剂

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最新的Smoothened抑制剂

GANT61 : Inhibitor for GLI1 as well as GLI2-induced transcription, inhibits hedgehog with IC50 of 5 μM, displays selectivity over other pathways, such as TNF and glucocorticoid receptor gene transactivation.
Smoothened激活剂

Purmorphamine : Directly binds and activates Smoothened, and blocks BODIPY-cyclopamine binding to Smo with IC50 of ~ 1.5 μM.

研究领域

产品类型

定制您的化合物库

Vismodegib (GDC-0449)

客户使用Selleck生产的Vismodegib (GDC-0449)发表文献164篇：

产品安全说明书

Hedgehog/Smoothened抑制剂选择性比较

生物活性

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

参考文献

溶解度 (25°C)

化学数据 Download Vismodegib (GDC-0449) SDF

动物体内配方计算器 (澄清溶液)

计算器

摩尔浓度计算器

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

稀释计算器

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

连续稀释计算器方程

连续稀释

计算结果

分子量计算器

总分子量：g/mol

摩尔浓度计算器

临床试验信息 (data from https://clinicaltrials.gov, updated on 2022-01-17)

技术支持

Hedgehog/Smoothened Signaling Pathway Map

Hedgehog/Smoothened Inhibitors with Unique Features

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