Vismodegib (GDC-0449)

Catalog No.S1082

For research use only.

Vismodegib (GDC-0449) is a potent, novel and specific hedgehog inhibitor with IC50 of 3 nM and also inhibits P-gp with IC50 of 3.0 μM in a cell-free assay.

Vismodegib (GDC-0449) Chemical Structure

CAS No. 879085-55-9

Selleck's Vismodegib (GDC-0449) has been cited by 165 publications

Purity & Quality Control

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Biological Activity

Description Vismodegib (GDC-0449) is a potent, novel and specific hedgehog inhibitor with IC50 of 3 nM and also inhibits P-gp with IC50 of 3.0 μM in a cell-free assay.
Targets
Hedgehog [1]
(Cell-free assay)
3 nM
In vitro

GDC-0449 targets the Hedgehog signaling pathway, blocking the activities of the Hedgehog-ligand cell surface receptors PTCH and/or SMO and suppressing Hedgehog signaling. GDC-0449 prevents multiple ATP-binding cassette (ABC) transporters. GDC-0449 also blocks ABCG2, Pgp, and MRP1-important ABC transporters associated with MDR. GDC-0449 is a potent inhibitor of ABC transporters, ABCG2/BCRP and ABCB1/Pgp, and is a mild inhibitor of ABCC1/MRP1. In ABCG2-overexpressing HEK293 cells, GDC-0449 increases retention of the fluorescent ABCG2 substrate BODIPY-prazosin and resensitizes these cells to mitoxantrone. In Madin-Darby canine kidney II cells engineered to overexpress Pgp or MRP1, GDC-0449 increases the retention of calcein-AM and resensitizes them to colchicine. GDC-0449 also resensitizes human non-small cell lung carcinoma cells NCI-H460/par and NCI-H460/MX20, which overexpress ABCG2 in response to mitoxantrone, to mitoxantrone, and to topotecan or SN-38. The IC50 values of GDC-0449 for prevention of ABCG2 and Pgp are about 1.4 μM and 3.0 μM, respectively. [2] GDC-0449 alters intracellular Ca2+ homeostasis and inhibits cell growth in cisplatin-resistant lung cancer cells. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
IGROV-1 MnP5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlL4TWM2OD1yLkC3NlQ5KM7:TR?= MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly0O|M1OTdxJ{7TRW5ITVJ:L3G+
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D-542MG NUezVHliT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4Oz[mlEPTB;MT64Olc{PyEQvF2= MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly0O|M1OTdxJ{7TRW5ITVJ:L3G+
23132-87 Mn\wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXPJR|UxRTRwNECxOFch|ryP M4HwVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFQ4OzRzNz:nQnNCVkeHUkyvZV4>
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ACN NGmzOJdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVPHSmVZUUN3ME24MlUxOTB7IN88US=> MmXrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOFc{PDF5Lze+V2FPT0WUPD;hQi=>
HuO-3N1 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NG\JZVBKSzVyPUmuOlAyODhizszN MmfCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOFc{PDF5Lze+V2FPT0WUPD;hQi=>
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KYSE-150 NF\PWHdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWrJR|UxRTFzLkW4OFEh|ryP NEDnd2w9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw1PzN2MUevK|5USU6JRWK8M4E,
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MDA-MB-361 M4fjVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3L6bmlEPTB;MUeuNlcyOSEQvF2= MmTPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOFc{PDF5Lze+V2FPT0WUPD;hQi=>
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NCI-SNU-1 NVPUUFZ1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{GzNmlEPTB;MkCuNFE6PiEQvF2= M1K3blxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFQ4OzRzNz:nQnNCVkeHUkyvZV4>
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LB2241-RCC MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWDJR|UxRTJzLki0OFEh|ryP Mmq2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOFc{PDF5Lze+V2FPT0WUPD;hQi=>
COLO-829 NVr3RYpXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEe4enVKSzVyPUKyMlE5PzFizszN NWrhXopjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPDd|NEG3M{c,W0GQR1XSQE9iRg>?
EW-11 NXfo[mFOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXvJR|UxRTJ{LkiwNlIh|ryP MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly0O|M1OTdxJ{7TRW5ITVJ:L3G+
NCI-H526 MnTPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYfJR|UxRTJ|LkS3NVch|ryP MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly0O|M1OTdxJ{7TRW5ITVJ:L3G+
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Calu-6 Mk[5SpVv[3Srb36gZZN{[Xl? NXT2XllxWGyjc33hJINwdmOnboTyZZRqd25iaX6gR4FtfS14IHPlcIx{KHinbn;ndoFnfGWmIH71[IUhdW:3c3WgVGswWERibX;k[Ywh[XRiN{WgcYcwc2duIIDvJIJq\CCob4KgOUBl[Xm|IH3lZZN2emWmIESgbJJ{KHCxc4SgcIF{fCCmb4PlJJJmdGG2aY\lJJRwKHWwdILlZZRm\CClb370do9tNCCFcDC9JFI{KM7:TT6= NIntOJI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEi3OVc1OSd-MkC4O|U4PDF:L3G+
T47D NUfD[3BPS3m2b4TvfIlkcXS7IHHzd4F6 MnrhO|IhcHK| NHTVZlVEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBVPDeGIHPlcIx{KGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEmFNUCgQUA1OS5|NDFOwG0v NVnm[WMyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmxNFc1OjlpPkK5NVA4PDJ7PD;hQi=>
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medulloblastoma cell MVjBcpRqfHWvb4KgZZN{[Xl? MUfBcpRqfHWvb4KgZYN1cX[rdImgZYdicW6|dDDtc5V{\SCvZXT1cIxw[myjc4TvcYEh[2WubIOgfIVvd2e{YX\0[YQhcW5iUITjbEAsNy1ibX;1d4Uh[XO|ZYPz[YQh[XNiZHXjdoVie2ViaX6geJVud3Jidn;seY1mKGG2IEGyMlUhdWdxa3esJJBwKGKrZD6= Mn70QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl5MU[yPVYoRjF7N{G2Nlk3RC:jPh?=
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A549 M2XFXmFvfGmycn;sbYZmemG2aY\lJIF{e2G7 NX\WdFZXOTBidV2= MoXyOFghcHK| MWnBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEF3NEmgZ4VtdHNiYYPz[ZN{\WRiYYOg[5Jwf3SqIHnubIljcXSrb36gZZQhOTBidV2gZYZ1\XJiNEigbJJ{KGK7IF3UWEBie3OjeT6= NWHHRWZ4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0PVE1PTlpPkK0OFkyPDV7PD;hQi=>
HCT116 NVHEWlRZSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= M4DVblExKHWP NH3OcJU1QCCqcoO= M4Xud2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFPUNVE3KGOnbHzzJIF{e2W|c3XkJIF{KGe{b4f0bEBqdmirYnn0bY9vKGG2IEGwJJVOKGGodHXyJFQ5KGi{czDifUBOXFRiYYPzZZkv Mkn3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2OUG0OVkoRjJ2NEmxOFU6RC:jPh?=
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MSC NFv0e|dHfW6ldHnvckBie3OjeR?= NHf3bJAzOCC2bzC4NEB2VQ>? M1TB[2lvcGmkaYTpc44hd2ZiaHXk[4Vpd2dic3nncoFtcW6pIHnuJI1wfXOnIF3TR{Bk\WyuczDhd5Nme3OnZDDhd{Bld3ewIILl[5Vt[XSrb36gc4Yh[WytYXzpcoUheGixc4DoZZRie2ViYYSgNlAhfG9iOECgeW0v MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR7MUS1PUc,OjR2OUG0OVk9N2F-
SK-N-MC M4PtWJFJXFNiYYPzZZk> NYDx[Zk3eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPLMW4uVUNiY3XscJMv NXPJSmI{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
TC32 MX;xTHRUKGG|c3H5 NEj1TJJyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBVSzN{IHPlcIx{Ng>? M1jGcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
NIH3T3-Luc MonJSpVv[3Srb36gZZN{[Xl? M3vHW|EhfU1? MoK4OFghcHK| Mk\DTY5pcWKrdHnvckBw\iC|bX:tcYVlcWG2ZXSgbIVl\2Wqb3egd4lodmGuaX7nJJBifGi5YYmgbY4hdW:3c3WgUmlJO1R|LVz1Z{Bk\WyuczDhd5Nme3OnZDDhd{Bld3ewcnXneYxifGmxbjDv[kBIdGlibWLORUBmgHC{ZYPzbY9vKGG2IEGgeW0h[W[2ZYKgOFghcHK|IHL5JJJm[WxvdHnt[UBRS1JiYX7hcJl{cXNw NWrGZVhYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0PVk1QDNpPkK5OFk6PDh|PD;hQi=>
C3H10T1/2 NVnlPXZMTnWwY4Tpc44h[XO|YYm= NVfFZ|VkOjRiaILz NI\ZTWJKdmirYnn0bY9vKG:oIHjl[IdmcG:pIIPp[45idGmwZzDwZZRpf2G7LX3l[IlifGWmIFfMTVEhdVKQQTDlfJBz\XO|aX;uJIlvKG2xdYPlJGM{UDFyVEGvNkBk\WyuczDh[pRmeiB{NDDodpMh[nliUmStVGNTKGGwYXz5d4l{KGmwIIDy[ZNmdmOnIH;mJEgyWix|YWKsOHMtP2GUKT23ZU1u\XSqeXytNU0pMFJrLU[tcYV1cHmuaHXweIFvNTJveXypc4N1[Wi7ZILvMVFJNWmwZHXuMVQugWxiMz3ofYRzd3i7YnXufo9ifGVw MoTsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR5M{C5PFQoRjJ2N{OwPVg1RC:jPh?=
C3H10T1/2 NVHQUoV{TnWwY4Tpc44h[XO|YYm= NV\L[INwOjRiaILz Mo[zTY5pcWKrdHnvckBw\iCqZXTn[Yhw\yC|aXfuZYxqdmdicHH0bJdigS2vZXTpZZRm\CCJTFmxJI1TVkFiZYjwdoV{e2mxbjDpckBud3W|ZTDDN2gyOFRzL{KgZ4VtdHNiYX\0[ZIhOjRiaILzJIJ6KFKWLWDDVkBidmGueYPpd{BqdiCycnXz[Y5k\SCxZjDWSFMv NFfMUJg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEezNFk5PCd-MkS3N|A6QDR:L3G+
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medulloblastoma cell NIDNTopCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= NUL0S5VsfXBidH:gN|AhfU1? MlTjO|IhcHK| MnzQRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDtc5V{\SCSdHPoL{8uKHB3Mz2vMUBu\WS3bHzvZoxie3SxbXGgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKGOnbHygdJJwdGmoZYLheIlwdiC3cDD0c{A{OCC3TTDh[pRmeiB5MjDodpMh[nliTWTTJIF{e2G7Lh?= M3vWeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6OEezN|A{Lz5{OEi3N|MxOzxxYU6=
medulloblastoma cell MlL2RZBweHSxc3nzJIF{e2G7 M4fKVGlv\HWldHnvckBw\iCjcH;weI9{cXNiaX6gcY92e2ViUITjbEswNSCyNUOtM{0hdWWmdXzsc4Jt[XO2b33hJINmdGy|IHntdIxidnSnZDDpckBifGi7bXnjJI52\GVibX;1d4Uh[XRiMUKuOUBu\y:tZzygbZAh[mmmIH\vdkAyPSClb37z[YN2fGm4ZTDkZZl{KGK7IGTVUmVNKGG|c3H5Mi=> MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDh5M{OwN{c,Ojh6N{OzNFM9N2F-
NIH/3T3 M1jtUGZ2dmO2aX;uJIF{e2G7 M37pTWlvcGmkaYTpc44hd2ZiaHXk[4Vpd2dic3nncoFtcW6pIIDheIh4[XliZYjwdoV{e2WmIHnuJI1wfXOnIF7JTE8{XDNiY3XscJMh[XO|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBp\WSpZXjv[{1qdmS3Y3XkJGdtcS1{IHHjZ5VufWyjdHnvckBifCC2aYCgc4YheHKrbXHyfUBkcWyrYTDifUBFSVCLIIP0ZYlvcW6pIHLhd4VlKGOxbn\vZ4FtKG2rY4Lvd4NweGmlIHHuZYx6e2m|Lh?= MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzhzMEW5NUc,Ojd6MUC1PVE9N2F-
NIH/3T3 NYjONVFvTnWwY4Tpc44h[XO|YYm= MVzJcohq[mm2aX;uJI9nKGinZHflbI9oKHOrZ37hcIlv\yCyYYToe4F6KGmwIH3veZNmKE6LSD:zWFMh[2WubIOgZZN{\XO|ZXSgZZMhcW6qaXLpeIlwdiCxZjDo[YRo\WixZz3pcoR2[2WmIGPtc{1GT0[SIHPpcIlienlidILhcpNtd2OjdHnvckBjgSCGQWDJJJN1[WmwaX7nJIJie2WmIHPvcoZw[2GuIH3pZ5Jwe2OxcHnjJIFv[Wy7c3nzMi=> M{exSlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5OEGwOVkyLz5{N{ixNFU6OTxxYU6=
medulloblastoma cell M{XURmFvfGlvdIXtc5Ih[XO|YYm= Mlj6RY51cS22dX3vdkBi[3Srdnn0fUBi\2GrboP0JI1wfXOnIGD0Z4gsNy1icEWzMU8uKG2nZIXscI9jdGG|dH;tZUBk\WyuczDpcZBt[W62ZXSgbY4h[XSqeX3pZ{BvfWSnIH3veZNmKGG|c3Xzd4VlKGG|IIT1cY9zKGe{b4f0bEBqdmirYnn0bY9vKGG2IEKwJI1oN2upLDDwc{Bi\G2rbnnzeIVz\WRidIfpZ4Uh\GGrbImgeoliKGejdnHn[UBu\WG|dYLl[EBmfmW{eTDveIhmeiCmYYmg[JVzcW6pIHPvcZBwfW6mIHTvd4lv\y5? NWLKTYY4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm3N|k4OTRpPkK5O|M6PzF2PD;hQi=>
C3H10T1/2 NEPzcVBHfW6ldHnvckBie3OjeR?= NEf1NIM1NjFidH:gNVAxOCCwTR?= MYjBcIxwe3SncnnjJIlvcGmkaYTpc44hd2ZiU33vJIlvKG2xdYPlJGM{UDFyVEGvNkBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIID1do1wenCqYX3pcoUucW6mdXPl[EBIdGlzIITyZY5{[3KrcITpc45idCCjY4Tpeol1gSCjdDC0MlEhfG9iMUCwNEBvVSCkeTDxVGNzKGGwYXz5d4l{Ng>? NYLTOlhFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwO|Q2PDFpPkKzNFc1PTRzPD;hQi=>
C3H10T1/2 NI\GZZVHfW6ldHnvckBie3OjeR?= Mm[5OE4yKHSxIEGwNFAhdk1? MmnRR49ueGW2aYTpeoUhcW6qaXLpeIlwdiCxZjDTcY8hcW5ibX;1d4UhSzOKMUDUNU8zKGOnbHzzJIF{e2W|c3XkJIF{KGmwaHnibZRqd25ib3[gV2FINWmwZIXj[YQhT2yrMTD0doFve2O{aYD0bY9v[WxiYXP0bZZqfHliYYSgOE4yKHSxIEGwNFAhdk1iYomgdXBEWiCjbnHsfZNqey5? M2ruWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MEe0OVQyLz5{M{C3OFU1OTxxYU6=
Assay
Methods Test Index PMID
Western blot Bcl-2 / Bax ; p53 / Cyclin D1 / p21 ; Gli1 / SOX2 / OCT4 ; p-GSK3β / GSK3β / p-Akt / Akt / Gli1 ; Fas / DR4 / DR5 / Cleaved PARP / Bcl-2 / Cleaved caspase-3 / PDGFRα 28195165 26418365 27143997 22087285
Immunofluorescence Gli1 / Gli2 22087285
Growth inhibition assay Cell viability 29042665
In vivo GDC-0449 has been used to treat medulloblastoma in animal models. [2] GDC-0449 prevents the growth of primary pancreatic xenografts without non-specifically inhibiting pancreatic cell proliferation. Oral dosing of GDC-0449 causes tumor regressions in the Ptch(+/-) allograft model of medulloblastoma at doses ≥25 mg/kg and tumor growth inhibition at doses up to 92 mg/kg dosed twice daily in two ligand-dependent colorectal cancer models, D5123, and 1040830. Analysis of Hh pathway activity and PK/PD modeling reveals that GDC-0449 inhibits Gli1 with a similar IC50 in both the medulloblastoma and D5123 models (0.165 μM and 0.267 μM, respectively). Pathway modulation is linked to efficacy using an integrated PK/PD model revealing a steep relationship where > 50% of the activity of GDC-0449 is associated with >80% repression of the Hh pathway. [4]

Protocol (from reference)

Cell Research:[2]
  • Cell lines: MDCKII cells
  • Concentrations: 20 μM
  • Incubation Time: 2 hours
  • Method: MDCKII cells are seeded into 24-well plates at a density of 3 × 105 cells per well and are allowed to attach. Medium is then changed to that containing different drugs (50 μM VP, 50 μM indomethacin, or 20 μM GDC-0449 in DMSO or DMSO alone as control, and nonfluorescent calcein-AM is added to a final concentration of 1.0 μM and incubated at 37 °C for 2 hours. Cells are then washed twice with Ca2+, Mg2+-containing Hank's balanced salt solution buffer and lysed by shaking in 0.01% Triton X-100 in PBS buffer for 1 hour at room temperature or overnight at 4 °C. The lysate is then transferred into 96-well plates, and the fluorescence signal caused by the cell-derived calcein is quantified spectrophotometrically with a SpectraMax M5 Multi-Detection Readerusing an excitation wavelength of 495 nm and an emission wavelength of 515 nm. All manipulations are performed in the dark. All readings are expressed as mean ?SEM normalized to the control.
  • (Only for Reference)
Animal Research:[4]
  • Animal Models: Ptch(+/-) allograft model, D5123 and 1040830
  • Dosages: ~ 100 mg/kg
  • Administration: Orally
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 84 mg/mL
(199.38 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
5% DMSO+40% PEG 300+5% Tween 80+50% ddH2O
For best results, use promptly after mixing.

12.5mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 421.3
Formula

C19H14Cl2N2O3S

CAS No. 879085-55-9
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CS(=O)(=O)C1=CC(=C(C=C1)C(=O)NC2=CC(=C(C=C2)Cl)C3=CC=CC=N3)Cl

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

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

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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