Vismodegib (GDC-0449)

For research use only.

Catalog No.S1082

153 publications

Vismodegib (GDC-0449) Chemical Structure

CAS No. 879085-55-9

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.

Selleck's Vismodegib (GDC-0449) has been cited by 153 publications

Purity & Quality Control

Choose Selective Hedgehog/Smoothened Inhibitors

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 NUnvPZp2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NET1RYNKSzVyPUCuNFczPDhizszN MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly0O|M1OTdxJ{7TRW5ITVJ:L3G+
HCE-T NWraU3ZmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGPiV49KSzVyPUGuN|IzPDdizszN M1zzW|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFQ4OzRzNz:nQnNCVkeHUkyvZV4>
D-542MG Mn\RS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEKyWIVKSzVyPUGuPFY4OzdizszN NIjvNY49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw1PzN2MUevK|5USU6JRWK8M4E,
23132-87 NGiwW3FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NELEeIhKSzVyPUSuOFAyPDdizszN MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly0O|M1OTdxJ{7TRW5ITVJ:L3G+
HDLM-2 MmTES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2CxWGlEPTB;OD6wOFc3PiEQvF2= M4mwNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFQ4OzRzNz:nQnNCVkeHUkyvZV4>
ACN Mk\WS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX2xTVhJUUN3ME24MlUxOTB7IN88US=> MlfxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOFc{PDF5Lze+V2FPT0WUPD;hQi=>
HuO-3N1 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFr6OllKSzVyPUmuOlAyODhizszN MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly0O|M1OTdxJ{7TRW5ITVJ:L3G+
BHT-101 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVrJR|UxRTFzLkO4JO69VQ>? NFr5Zo89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw1PzN2MUevK|5USU6JRWK8M4E,
KYSE-150 NYCxcWN2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4r4RWlEPTB;MUGuOVg1OSEQvF2= NXHkNYZjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPDd|NEG3M{c,W0GQR1XSQE9iRg>?
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NB7 MkTtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlvOTWM2OD1zNT64PVEh|ryP MkDOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOFc{PDF5Lze+V2FPT0WUPD;hQi=>
DMS-273 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1zTUmlEPTB;MU[uOlcyOyEQvF2= M4PUVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFQ4OzRzNz:nQnNCVkeHUkyvZV4>
MDA-MB-361 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlT6TWM2OD1zNz6yO|EyKM7:TR?= MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly0O|M1OTdxJ{7TRW5ITVJ:L3G+
DU-145 MnjNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV3JR|UxRTF6LkOyJO69VQ>? M3uwR|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFQ4OzRzNz:nQnNCVkeHUkyvZV4>
NCI-H82 M1v2Rmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4\HWWlEPTB;MUmuPFM5PiEQvF2= M2XR[|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFQ4OzRzNz:nQnNCVkeHUkyvZV4>
NCI-SNU-1 MkTwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWTyTZJ3UUN3ME2yNE4xOTl4IN88US=> MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly0O|M1OTdxJ{7TRW5ITVJ:L3G+
GCT NVXiOmI3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX7wXmZUUUN3ME2yNE45QDJ2IN88US=> MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly0O|M1OTdxJ{7TRW5ITVJ:L3G+
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LB2241-RCC MoXMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M123d2lEPTB;MkGuPFQ1OSEQvF2= MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly0O|M1OTdxJ{7TRW5ITVJ:L3G+
COLO-829 Mnm1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{H3U2lEPTB;MkKuNVg4OSEQvF2= NFjqW4g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw1PzN2MUevK|5USU6JRWK8M4E,
EW-11 M{frR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVrhNYo6UUN3ME2yNk45ODJ{IN88US=> NUD1VXlSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPDd|NEG3M{c,W0GQR1XSQE9iRg>?
NCI-H526 Mn7QS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWnrXpM3UUN3ME2yN{41PzF5IN88US=> NX30fm5TRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPDd|NEG3M{c,W0GQR1XSQE9iRg>?
SF295 MnnqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGjnTnhKSzVyPUK0MlAzPTJizszN MlHLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOFc{PDF5Lze+V2FPT0WUPD;hQi=>
D-566MG MofMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXfNb4ZDUUN3ME2yOU4zQTR|IN88US=> MnLJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOFc{PDF5Lze+V2FPT0WUPD;hQi=>
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QIMR-WIL MnfyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIfldlZKSzVyPUO4MlA4ODhizszN NIr3bHo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw1PzN2MUevK|5USU6JRWK8M4E,
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HCC1806 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWnJR|UxRTR4LkGxOFgh|ryP M1nwTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFQ4OzRzNz:nQnNCVkeHUkyvZV4>
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medulloblastoma cell M2nJbmFvfGm2dX3vdkBie3OjeR?= MYfBcpRqfHWvb4KgZYN1cX[rdImgZYdicW6|dDDtc5V{\SCvZXT1cIxw[myjc4TvcYEh[2WubIOgfIVvd2e{YX\0[YQhcW5iUITjbEAsNy1ibX;1d4Uh[XO|ZYPz[YQh[XNiZHXjdoVie2ViaX6geJVud3Jidn;seY1mKGG2IEGyMlUhdWdxa3esJJBwKGKrZD6= MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTdzNkK5Okc,OTl5MU[yPVY9N2F-
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medulloblastoma cell NH3FepZCeG:ydH;zbZMh[XO|YYm= NHHnfJpKdmS3Y4Tpc44hd2ZiYYDvdJRwe2m|IHnuJI1wfXOnIGD0Z4gsNy1icEWzMU8uKG2nZIXscI9jdGG|dH;tZUBk\WyuczDpcZBt[W62ZXSgbY4h[XSqeX3pZ{BvfWSnIH3veZNmKGG2IEGyMlUhdWdxa3esJIlxKGKrZDDmc5IhOTViY3;ud4VkfXSrdnWg[IF6eyCkeTDUWW5GVCCjc4PhfU4> M4XiWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6OEezN|A{Lz5{OEi3N|MxOzxxYU6=
NIH/3T3 NGLXXVZHfW6ldHnvckBie3OjeR?= MmrBTY5pcWKrdHnvckBw\iCqZXTn[Yhw\yC|aXfuZYxqdmdicHH0bJdigSCneIDy[ZN{\WRiaX6gcY92e2ViTlnIM|NVOyClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJIhm\GenaH;nMYlv\HWlZXSgS4xqNTJiYXPjeY12dGG2aX;uJIF1KHSrcDDv[kBxemmvYYL5JINqdGmjIHL5JGRCWElic4ThbY5qdmdiYnHz[YQh[2:wZn;jZYwhdWmlcn;zZ49xcWNiYX7hcJl{cXNw NF\TV5g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{ixNFU6OSd-Mke4NVA2QTF:L3G+
NIH/3T3 NH3NW|ZHfW6ldHnvckBie3OjeR?= MYfJcohq[mm2aX;uJI9nKGinZHflbI9oKHOrZ37hcIlv\yCyYYToe4F6KGmwIH3veZNmKE6LSD:zWFMh[2WubIOgZZN{\XO|ZXSgZZMhcW6qaXLpeIlwdiCxZjDo[YRo\WixZz3pcoR2[2WmIGPtc{1GT0[SIHPpcIlienlidILhcpNtd2OjdHnvckBjgSCGQWDJJJN1[WmwaX7nJIJie2WmIHPvcoZw[2GuIH3pZ5Jwe2OxcHnjJIFv[Wy7c3nzMi=> MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzhzMEW5NUc,Ojd6MUC1PVE9N2F-
medulloblastoma cell NWW0W45RSW62aT30eY1weiCjc4PhfS=> NG\lOmxCdnSrLYT1cY9zKGGldHn2bZR6KGGpYXnud5QhdW:3c3WgVJRkcCtxLTDwOVMuNy1ibXXkeYxtd2KuYYP0c41iKGOnbHzzJIlueGyjboTl[EBqdiCjdHj5cYlkKG63ZHWgcY92e2ViYYPz[ZN{\WRiYYOgeJVud3JiZ4Lve5RpKGmwaHnibZRqd25iYYSgNlAhdWdxa3esJJBwKGGmbXnubZN1\XKnZDD0e4lk\SCmYXnsfUB3cWFiZ3H2ZYdmKG2nYYP1doVlKGW4ZYL5JI91cGW{IHThfUBlfXKrbnegZ49ueG:3bnSg[I9{cW6pLh?= NUOxPWlLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm3N|k4OTRpPkK5O|M6PzF2PD;hQi=>
C3H10T1/2 MWrGeY5kfGmxbjDhd5NigQ>? NFvoWJQ1NjFidH:gNVAxOCCwTR?= MniwRYxtd3O2ZYLpZ{BqdmirYnn0bY9vKG:oIGPtc{BqdiCvb4Xz[UBEO0hzMGSxM|Ih[2WubIOgZZN{\XO|ZXSgZZMhcW6qaXLpeIlwdiCxZjDweZJud3KyaHHtbY5mNWmwZIXj[YQhT2yrMTD0doFve2O{aYD0bY9v[WxiYXP0bZZqfHliYYSgOE4yKHSxIEGwNFAhdk1iYomgdXBEeiCjbnHsfZNqey5? M3zqZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MEe0OVQyLz5{M{C3OFU1OTxxYU6=
C3H10T1/2 NYniVVZMTnWwY4Tpc44h[XO|YYm= NELoUGg1NjFidH:gNVAxOCCwTR?= MUnDc41x\XSrdHn2[UBqdmirYnn0bY9vKG:oIGPtc{BqdiCvb4Xz[UBEO0hzMGSxM|Ih[2WubIOgZZN{\XO|ZXSgZZMhcW6qaXLpeIlwdiCxZjDTRWcucW6mdXPl[EBIdGlzIITyZY5{[3KrcITpc45idCCjY4Tpeol1gSCjdDC0MlEhfG9iMUCwNEBvVSCkeTDxVGNTKGGwYXz5d4l{Ng>? MojHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjNyN{S1OFEoRjJ|MEe0OVQyRC:jPh?=

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
Bcl-2 / Bax; 

PubMed: 28195165     


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     


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     


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     


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     


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     


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     


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
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

Cell Research:[2]
- Collapse
  • 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]
- Collapse
  • 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 powder
in solvent
Synonyms N/A
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)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
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Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
    Concentration
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*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and SDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • 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):
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    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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 Active not recruiting Drug: Vismodegib Carcinoma Basal Cell University of Michigan Rogel Cancer Center July 15 2015 Phase 4

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

Tel: +1-832-582-8158 Ext:3

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID