Nintedanib (BIBF 1120)

For research use only.

Catalog No.S1010 Synonyms: Intedanib, Vargatef, Ofev

86 publications

Nintedanib (BIBF 1120) Chemical Structure

CAS No. 656247-17-5

Nintedanib (BIBF 1120, Intedanib, Vargatef, Ofev) is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM in cell-free assays. Phase 3.

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Selleck's Nintedanib (BIBF 1120) has been cited by 86 publications

Purity & Quality Control

Choose Selective VEGFR Inhibitors

Biological Activity

Description Nintedanib (BIBF 1120, Intedanib, Vargatef, Ofev) is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM in cell-free assays. Phase 3.
Targets
VEGFR2 [1]
(Cell-free assay)
VEGFR3 [1]
(Cell-free assay)
LCK [1]
(Cell-free assay)
FLT3 [1]
(Cell-free assay)
VEGFR1 [1]
(Cell-free assay)
13 nM 13 nM 16 nM 26 nM 34 nM
In vitro

BIBF1120 inhibits PDGFR kinase activity of PDGFR alpha and PDGFR beta types with IC50 values of 59 nM and 65 nM, respectively. In addition, BIBF1120 suppresses the FGFR subtypes with IC50 of 60 nM, 37 nM and 108 nM for FGFR1, FGFR2, and FGFR3, respectively. BIBF1120 binds to the ATP-binding site in the cleft between the amino and carboxy terminal lobes of the kinase domain. The indolinone scaffold forms two hydrogen bonds with the backbone nitrogen of Cys919 and the backbone carbonyl oxygen of Glu917 in the hinge region. BIBF 1120 inhibits proliferation of PDGF-BB stimulated BRPs with EC50 of 79 nM in cell assays. BIBF1120 at concentrations as low as 100 nM blocks activation of MAPK after stimulation with 5% serum plus PDGF-BB. In cultures of human vascular smooth muscle cells (HUASMC), BIBF1120 prevents PDGF-BB stimulated proliferation with an EC50 of 69 nM. [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
SKOV3 MXfGeY5kfGmxbjDBd5NigQ>? NEPwOJc2KML3TR?= MXiyOEBp NY[1bGxTTE2VTx?= NUjh[pRwcW6mdXPld{BiKHOrZ37p[olk[W62IHnuZ5Jm[XOnIHnuJJRp\SCycn;tc5RmeiCjY4Tpeol1cWW|IH;mJGUu[2GmLNMgR2RJOSxiYX7kxsBETEh| NVTUV|VCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wOlE4PDdpPkK2NFYyPzR5PD;hQi=>
A549 Ml\5SpVv[3Srb36gRZN{[Xl? MkjKNk82KM7:TR?= MnfPNlQhcA>? NY\oVpRbTE2VTx?= NHTYdFlp[XNiYTDn[Y5memGuIFXNWEBz\X[ncoPhcEBm\m[nY4VCpC=> NXjGXIJWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wOlE4PDdpPkK2NFYyPzR5PD;hQi=>
T24 NH3UT5NHfW6ldHnvckBCe3OjeR?= NIP4[2czNzVizszN NV;Ke3QzOjRiaB?= M1zUZmROW09? Mne5bIF{KGFiZ3Xu[ZJidCCHTWSgdoV3\XK|YXyg[YZn\WO2wrC= NHeyZYo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC2NVc1Pyd-Mk[wOlE4PDd:L3G+
Mia-Paca2 M2TqSmZ2dmO2aX;uJGF{e2G7 NUXYOldrOi93IN88US=> MlXMNlQhcA>? M3H3SmROW09? M3XoS4hieyCjIHflcoVz[WxiRV3UJJJmfmW{c3HsJIVn\mWldNMg NUXCSohvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wOlE4PDdpPkK2NFYyPzR5PD;hQi=>
A549 MlfsSpVv[3Srb36gRZN{[Xl? NYnRbo13OC5yMfMAl|XDqM7:TR?= MWiyOEBp NEXuWndFVVOR MV7pcoR2[2W|IGPGWHBFyqCvUl7BJIV5eHKnc4Ppc44h\G:|ZTDk[ZBmdmSnboTsfS=> MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh2M{CwOUc,OjV6NEOwNFU9N2F-
A549 Mn\KSpVv[3Srb36gRZN{[Xl? MU[wMlAy6oDVNdMg{txO NUXoRoRUPzJiaB?= M{DobmROW09? NGXaN3BmdmijbnPld{BUWC2GIIDyc5RmcW5iZYjwdoV{e2mxbjDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6ncjDheEBkd26lZX70doF1cW:wczDv[kB2eCC2bzC1xsDPxE4EoB?= M3y5Z|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OESzNFA2Lz5{NUi0N|AxPTxxYU6=
A549 MonzSpVv[3Srb36gRZN{[Xl? M2jnTVXDqM7:TR?= M1zFdVAuOSCq MkT3SG1UVw>? NULCSXltcW6lcnXhd4V{KEGSLUGgZYN1cX[jdHnvckAh[W[2ZYKgN|AhdWmw NFXkUG09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUi0N|AxPSd-MkW4OFMxODV:L3G+
Hep3B M4jDVWNmdGxiVnnhZoltcXS7IFHzd4F6 NGW2UW4xNTJyIN88US=> M4HYelQ5yqCq MnzQ[IVkemWjc3XzJINmdGxidnnhZoltcXS7IHTvd4Uh\GWyZX7k[Y51dHl? MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDZ3N{O5PEc,OjR4NUezPVg9N2F-
HepG2 NWL2WnlNS2WubDDWbYFjcWyrdImgRZN{[Xl? MWmwMVIxKM7:TR?= MlLuOFjDqGh? Mn\Z[IVkemWjc3XzJINmdGxidnnhZoltcXS7IHTvd4Uh\GWyZX7k[Y51dHl? MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDZ3N{O5PEc,OjR4NUezPVg9N2F-
PLC5 MoS2R4VtdCCYaXHibYxqfHliQYPzZZk> MYOwMVIxKM7:TR?= NFzzSoE1QMLiaB?= NGLUVpRl\WO{ZXHz[ZMh[2WubDD2bYFjcWyrdImg[I9{\SCmZYDlcoRmdnSueR?= MkDkQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4NUezPVgoRjJ2NkW3N|k5RC:jPh?=
HuH7 NIrvbm5E\WyuIG\pZYJqdGm2eTDBd5NigQ>? NEXj[FYxNTJyIN88US=> Mm\rOFjDqGh? MWrk[YNz\WG|ZYOgZ4VtdCC4aXHibYxqfHliZH;z[UBl\XCnbnTlcpRtgQ>? NVrHWmVLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS2OVc{QThpPkK0OlU4Ozl6PD;hQi=>
SK-Hep1 M2jVdWNmdGxiVnnhZoltcXS7IFHzd4F6 NUW1[49iOC1{MDFOwG0> MV[0POKhcA>? M2PvdIRm[3KnYYPld{Bk\WyuII\pZYJqdGm2eTDkc5NmKGSncHXu[IVvfGy7 Mmr2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4NUezPVgoRjJ2NkW3N|k5RC:jPh?=
Hep3B NID5fJBCeG:ydH;zbZMhSXO|YYm= NEPabmwxNTJyIN88US=> M{[0ZlQ5yqCq M{nv[olv\HWlZYOgZ4VtdCCjcH;weI9{cXNiZH;z[UBl\XCnbnTlcpRtgQ>? M2XZ[|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NkW3N|k5Lz5{NE[1O|M6QDxxYU6=
HepG2 M2DLb2Fxd3C2b4Ppd{BCe3OjeR?= NHzHWIsxNTJyIN88US=> M{nRUlQ5yqCq M1fTRolv\HWlZYOgZ4VtdCCjcH;weI9{cXNiZH;z[UBl\XCnbnTlcpRtgQ>? Mmn3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4NUezPVgoRjJ2NkW3N|k5RC:jPh?=
PLC5 MknURZBweHSxc3nzJGF{e2G7 NXS0U2ZKOC1{MDFOwG0> NGHpcGg1QMLiaB?= MYnpcoR2[2W|IHPlcIwh[XCxcITvd4l{KGSxc3Wg[IVx\W6mZX70cJk> M1La[|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NkW3N|k5Lz5{NE[1O|M6QDxxYU6=
HuH7 NVz1[pN6SXCxcITvd4l{KEG|c3H5 NY\0WWV6OC1{MDFOwG0> Ml;zOFjDqGh? M1Lie4lv\HWlZYOgZ4VtdCCjcH;weI9{cXNiZH;z[UBl\XCnbnTlcpRtgQ>? MmqzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4NUezPVgoRjJ2NkW3N|k5RC:jPh?=
SK-Hep1 MlT3RZBweHSxc3nzJGF{e2G7 M1\DWlAuOjBizszN MoPwOFjDqGh? MYHpcoR2[2W|IHPlcIwh[XCxcITvd4l{KGSxc3Wg[IVx\W6mZX70cJk> MnrRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4NUezPVgoRjJ2NkW3N|k5RC:jPh?=
H1703 M4Tp[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Moi5TWM2OD1yLkC1JO69VQ>? NIGzPJo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{eyPVQxOyd-MkO3Nlk1ODN:L3G+
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Sf9 MmLrSpVv[3Srb36gZZN{[Xl? NYnsOGxXOjBibXnudy=> MYrJcohq[mm2aX;uJI9nKGi3bXHuJGdUXC2odYPl[EBXTUeIUkKg[ZhxemW|c3XkJIlvKFOoOTDpcpNm[3RiY3XscJMh[W[2ZYKgNlAhdWmwczDifUB{[2mwdHnscIF1cW:wIHPveY51cW6pLDDJR|UxKD1iMD6wNlEh|ryPLh?= MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDV3OUWyOEc,OTh3NUm1NlQ9N2F-
NIH3T3 NYD5[WwxTnWwY4Tpc44h[XO|YYm= NXLG[29ZPTBibl2= MVOxJIhz NXHFem44UW6qaXLpeIlwdiCxZjDWSWdHWjJidILhcpNn\WO2ZXSgbY4hdW:3c3WgUmlJO1R|IHPlcIx{KGG2IEWwJI5OKGmwY4XiZZRm\CCob4KgNUBpeiCvZXHzeZJm\CCjZoTldkA{OiCqcoOge4F{cG:3dDDmc4xtd3enZDDifUBXTUeIIIP0bY12dGG2aX;uJIZweiBzMDDtbY5{KGK7IGfld5Rmem5iYnzveJRqdmd? NF3Db5c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEW1PVUzPCd-MUi1OVk2OjR:L3G+
HT-29 MXjBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? M1vqXVczKGi{cx?= M{HxUWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSGStNlkh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OCB;IESuPUDPxE1w MnHIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjhzOUC2OVIoRjJ6MUmwOlUzRC:jPh?=
SKOV3 NYW3Z2YxSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= MmD6O|IhcHK| MWLBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFONT2[zJINmdGy|IHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVAhRSB{OD63OkDPxE1w NVjWUlBnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkixPVA3PTJpPkK4NVkxPjV{PD;hQi=>
BL21 (DE3) NUnydpRQTnWwY4Tpc44h[XO|YYm= MkT1N|AhdWmwcx?= MUfJcohq[mm2aX;uJI9nKEirc{[teIFo\2WmIF3FUGsh[2G2YXz5eIlkKGSxbXHpckApOSC2bzCzOFAhemW|aXT1[ZMqKCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIFXzZ4hmemmlaHnhJINwdGliQlyyNUApTEV|KTDj[YxteyC3c3nu[{BD[2xvR1ygZZMhe3Wkc4TyZZRmKG2nYYP1doVlKGGodHXyJFMxKG2rboOgbY4heHKnc3XuZ4Uhd2ZiW3fhcY1iOzKSXVHUVEBjgSCuaYH1bYQhe2OrboTpcIxifGmxbjDjc5VvfGmwZzDt[ZRpd2RuIFvpJF0hOC5yMEW2JO69VS5? NI\IS3o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEO1NVYxPyd-MkizOVE3ODd:L3G+
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A549 MULBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? M3P2bVczKGi{cx?= MUPBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEF3NEmgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NEA:KDJ{Lk[yJO69VS5? MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDh{NkC4OEc,Ojh6Mk[wPFQ9N2F-
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SJ-GBM2 NUHI[mg5eUiWUzDhd5NigQ>? NYq0Nmt7eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPKMWdDVTJiY3XscJM> MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
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LAN-5 NX;OSog6eUiWUzDhd5NigQ>? NYn3b3JYeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFzBUk02KGOnbHzz M3jNTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
NB1643 MnK1dWhVWyCjc4PhfS=> NWK2fm13eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhVkJzNkSzJINmdGy| MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
SK-N-MC MV3xTHRUKGG|c3H5 M33Yd5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHNMNU5vTVOgZ4VtdHN? M4f6OFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
TC32 MYrxTHRUKGG|c3H5 MW\xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDUR|MzKGOnbHzz NFXXTIk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
Rh18 NGHPTJdyUFSVIHHzd4F6 MkS2dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgVogyQCClZXzsdy=> NFHpSVQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
Fibronectin / Collagen 1a1; 

PubMed: 26072676     


(A and B) IPF fibroblasts were treated with increasing doses of nintedanib (0.5, 1, or 2 μM) (A) or nintedanib (2 μM) for increasing durations (24, 48, or 72 h) (B). Expression of fibronectin and collagen 1a1 was evaluated by Western immunoblotting.

p-SMAD3 / SMAD3 / p-p38 MAPK / p38 MAPK ; 

PubMed: 26072676     


IMR-90 fibroblasts were serum starved overnight and cotreated with or without TGF-β1 (2.5 ng/ml) and increasing doses of nintedanib (0.5, 1, and 2 μM) for 1 hour. Expression of pS423/425-SMAD3, SMAD3, pT180/Y182-p38 mitogen-activated protein kinase (MAPK), and p38 MAPK was evaluated by Western blotting. 

Cyclin A / Cyclin D1 / Cyclin E / CDK2 / CDK4 / CDK6; 

PubMed: 29934570     


Western blot based detection of cell cycle associated molecules viz., Cyclins A, D1 and E, and CDKs 2, 4 and 6 in PC3 cells after 72 hours of Nintedanib treatment. 

p-EGFR / FGFR1 / p-AKT / AKT / p-ERK / ERK; 

PubMed: 27581340     


Effects of nintedanib on FGFR1, ERK, and AKT phosphorylation in FGFR1 CNG‐positive lung squamous cell carcinoma cell lines. H520 and LK‐2 cells were incubated for 6 h in the presence of the indicated concentrations of nintedanib, after which cell lysates (25 μg soluble protein) were subjected to immunoblot analysis with antibodies to the indicated proteins.

26072676 29934570 27581340
Immunofluorescence
Vimentin / E-cadherin ; 

PubMed: 29934570     


Immunoflouresence staining for Vimentin (green) and E-cadherin (red) in DMSO control and 2.5 µM Nintedanib treated PC3 cells after 72 h of incubation. Representative flourescent pictures are shown at 600X. DAPI: 4′,6-diamidino-2-phenylindole.

29934570
In vivo In all tumor models tested thus far, including human tumor xenografts growing in nude mice and a syngeneic rat tumor model, BIBF1120 is highly active at well-tolerated doses (25-100 mg/kg daily p.o.). This is evident in the magnetic resonance imaging of tumor perfusion after 3 days, reducing vessel density and vessel integrity after 5 days, and profound growth inhibition. [1]

Protocol

Kinase Assay:[3]
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VEGFR2 Kinase Assay:

The cytoplasmic tyrosine kinase domain of VEGFR2 (residues 797-1355 according to sequence deposited in databank SWISS-PROT P35968) is cloned into pFastBac fused to GST and extracted. Enzyme activity is assayed in the presence or absence of serial dilutions of BIBF1120 performed in 25% DMSO. Each microtiter plate contains internal controls such as blank, maximum reaction, and historical reference compound. All incubations are conducted at room temperature on a rotation shaker. 10 μL of each BIBF1120 dilution is added to 10 μL of diluted kinase (0.8 μg/mL VEGFR2, 10 mM Tris pH 7.5, 2 mM EDTA, and 2 mg/mL BSA) and preincubated for 1 hour. The reaction is started by addition of 30 μL of substrate mix containing 62.4 mM Tris pH 7.5, 2.7 mM DTT, 5.3 mM MnCl2, 13.3 mM Mg-acetate, 0.42 mM ATP, 0.83 mg/mL Poly-Glu-Tyr(4:1), and 1.7 μg/mL Poly-Glu-Tyr(4:1)-biotin and incubated for 1 hour. The reaction is stopped by addition of 50 μL of 250 mM EDTA, 20 mM HEPES, pH 7.4. 90 μL of the reaction mix is transferred to a streptavidin plate and incubated for 1-2 hours. After three washes with PBS the EU-labeled antibody, PY20 is added (recommended dilution 1:2000 of 0.5 mg/mL labeled antibody in DELFIA assay buffer). Excessive detection antibody is removed by three washes of DELFIA washing buffer. Then 10 minutes before measurement on the multilabel reader, each well is incubated with 100 μL of DELFIA enhancement solution.
Cell Research:[1]
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  • Cell lines: HUVEC, HUASMC, and BRP cell lines
  • Concentrations: 50 nM
  • Incubation Time: 2 hours
  • Method: The cell lines HUVEC, HUASMC, and BRP are used for the assay. BIBF1120 is added to the cultures two hours before the addition of ligands. Cell lysates are generated. Western blotting is done using standard SDS-PAGE methods, loading 50 to 75 μg of protein per lane. Detection is facilitated by enhanced chemiluminescence. Total and phosphorylated mitogen-activated protein kinase (MAPK) is analyzed using monoclonal antibodies M3807 and M8159. Total Akt is detected using the corresponding polyclonal antibody and phosphorylated Akt (Ser473) is analyzed by using its monoclonal antibody. Monoclonal antibody is also used to detect cleaved caspase-3 while KDR (VEGFR2) protein is detected using a corresponding antibody.
    (Only for Reference)
Animal Research:[1]
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  • Animal Models: FaDu, Caki-1, SKOV-3, H460, HT-29, or PAC-120 xenografts in Athymic NMRI-nu/nu female mice
  • Dosages: 100 mg/kg
  • Administration: p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 6 mg/mL (11.11 mM)
Ethanol 3 mg/mL (5.55 mM)
Water 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+2% Tween 80+ddH2O
For best results, use promptly after mixing.
0.25mg/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 539.62
Formula

C31H33N5O4

CAS No. 656247-17-5
Storage powder
in solvent
Synonyms Intedanib, Vargatef, Ofev
Smiles CN1CCN(CC1)CC(=O)N(C)C2=CC=C(C=C2)N=C(C3=CC=CC=C3)C4=C(NC5=C4C=CC(=C5)C(=O)OC)O

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Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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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
NCT04525547 Not yet recruiting Drug: Nintedanib Idiopathic Pulmonary Fibrosis Boehringer Ingelheim December 31 2020 --
NCT04541680 Recruiting Drug: Nintedanib 150 MG [Ofev]|Other: Placebo SARS-Cov-2 Induced Pulmonary Fibrosis Assistance Publique - Hôpitaux de Paris|Boehringer Ingelheim October 29 2020 Phase 3
NCT03283007 Recruiting Drug: Nintedanib|Drug: Placebo Lung-transplant Recipients Assistance Publique - Hôpitaux de Paris October 30 2019 Phase 3
NCT03958071 Completed Drug: Nintedanib|Drug: Pirfenidone|Other: Untreated Cohort Idiopathic Pulmonary Fibrosis Boehringer Ingelheim February 1 2019 --
NCT03710824 Recruiting Drug: Nintedanib Idiopathic Pulmonary Fibrosis Boehringer Ingelheim February 28 2019 --

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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VEGFR Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID