Nintedanib (BIBF 1120)

For research use only.

Catalog No.S1010 Synonyms: Intedanib, Vargatef, Ofev

95 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.

Selleck's Nintedanib (BIBF 1120) has been cited by 95 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 MXTGeY5kfGmxbjDBd5NigQ>? MXG1JOK2VQ>? Moq4NlQhcA>? NGjtZ5dFVVOR NV\ETFRxcW6mdXPld{BiKHOrZ37p[olk[W62IHnuZ5Jm[XOnIHnuJJRp\SCycn;tc5RmeiCjY4Tpeol1cWW|IH;mJGUu[2GmLNMgR2RJOSxiYX7kxsBETEh| NI\od|g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC2NVc1Pyd-Mk[wOlE4PDd:L3G+
A549 MWLGeY5kfGmxbjDBd5NigQ>? MYiyM|Uh|ryP MonkNlQhcA>? M4\IeWROW09? NIj3fIpp[XNiYTDn[Y5memGuIFXNWEBz\X[ncoPhcEBm\m[nY4VCpC=> Ml\nQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyNkG3OFcoRjJ4ME[xO|Q4RC:jPh?=
T24 MmPvSpVv[3Srb36gRZN{[Xl? NHnHRWwzNzVizszN MVSyOEBp MmfYSG1UVw>? MnXmbIF{KGFiZ3Xu[ZJidCCHTWSgdoV3\XK|YXyg[YZn\WO2wrC= M2fZVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4ME[xO|Q4Lz5{NkC2NVc1PzxxYU6=
Mia-Paca2 M3X0VmZ2dmO2aX;uJGF{e2G7 MWiyM|Uh|ryP MoPvNlQhcA>? M4TQO2ROW09? NGL2eG5p[XNiYTDn[Y5memGuIFXNWEBz\X[ncoPhcEBm\m[nY4VCpC=> M1rZWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4ME[xO|Q4Lz5{NkC2NVc1PzxxYU6=
A549 MXXGeY5kfGmxbjDBd5NigQ>? M2rtdlAvODIkgKO1xsDPxE1? M1zuPFI1KGh? NF;ETmFFVVOR Mn7DbY5lfWOnczDTSnRRTMLibWLORUBmgHC{ZYPzbY9vKGSxc3Wg[IVx\W6mZX70cJk> MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh2M{CwOUc,OjV6NEOwNFU9N2F-
A549 MknKSpVv[3Srb36gRZN{[Xl? NELV[4cxNjBz4pETOeKh|ryP MUm3NkBp M{LFUmROW09? MkXI[Y5p[W6lZYOgV3AuTCCycn;0[YlvKGW6cILld5Nqd25iaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XJiYYSgZ49v[2WwdILheIlwdnNib3[geZAhfG9iNdMg{txOyqB? MnLtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6NEOwNFUoRjJ3OESzNFA2RC:jPh?=
A549 NVTnc3pTTnWwY4Tpc44hSXO|YYm= MUS1xsDPxE1? M13oSlAuOSCq NY\ZbZFjTE2VTx?= NWrwfmJWcW6lcnXhd4V{KEGSLUGgZYN1cX[jdHnvckAh[W[2ZYKgN|AhdWmw NX7xeHBPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4OFMxODVpPkK1PFQ{ODB3PD;hQi=>
Hep3B NXewc5NkS2WubDDWbYFjcWyrdImgRZN{[Xl? MWWwMVIxKM7:TR?= MYC0POKhcA>? M{n4PYRm[3KnYYPld{Bk\WyuII\pZYJqdGm2eTDkc5NmKGSncHXu[IVvfGy7 M37X[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NkW3N|k5Lz5{NE[1O|M6QDxxYU6=
HepG2 NGPkT|dE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MX:wMVIxKM7:TR?= NXHkdFRSPDkEoHi= M4PMOYRm[3KnYYPld{Bk\WyuII\pZYJqdGm2eTDkc5NmKGSncHXu[IVvfGy7 M3jvWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NkW3N|k5Lz5{NE[1O|M6QDxxYU6=
PLC5 MXXD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MVewMVIxKM7:TR?= NHH6eHo1QMLiaB?= NYHLOo5L\GWlcnXhd4V{KGOnbHygeoli[mmuaYT5JIRwe2ViZHXw[Y5l\W62bIm= Ml;EQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4NUezPVgoRjJ2NkW3N|k5RC:jPh?=
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SK-Hep1 MVnD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M{\OOlAuOjBizszN Mn:2OFjDqGh? M3TqdYRm[3KnYYPld{Bk\WyuII\pZYJqdGm2eTDkc5NmKGSncHXu[IVvfGy7 NV\hSmhyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS2OVc{QThpPkK0OlU4Ozl6PD;hQi=>
Hep3B MmLpRZBweHSxc3nzJGF{e2G7 MlS4NE0zOCEQvF2= NGrFb|U1QMLiaB?= NIT3R5RqdmS3Y3XzJINmdGxiYYDvdJRwe2m|IHTvd4Uh\GWyZX7k[Y51dHl? M2GxW|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NkW3N|k5Lz5{NE[1O|M6QDxxYU6=
HepG2 M4XZTGFxd3C2b4Ppd{BCe3OjeR?= MWqwMVIxKM7:TR?= NH7LWJo1QMLiaB?= MlXlbY5lfWOnczDj[YxtKGGyb4D0c5NqeyCmb4PlJIRmeGWwZHXueIx6 MlLxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4NUezPVgoRjJ2NkW3N|k5RC:jPh?=
PLC5 NVrRWI5ZSXCxcITvd4l{KEG|c3H5 M1;l[VAuOjBizszN NISzZZY1QMLiaB?= MlvobY5lfWOnczDj[YxtKGGyb4D0c5NqeyCmb4PlJIRmeGWwZHXueIx6 NWLUbJlKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS2OVc{QThpPkK0OlU4Ozl6PD;hQi=>
HuH7 NUiyfHNzSXCxcITvd4l{KEG|c3H5 M1TUPFAuOjBizszN NY\TNpByPDkEoHi= NHz2SJFqdmS3Y3XzJINmdGxiYYDvdJRwe2m|IHTvd4Uh\GWyZX7k[Y51dHl? NF\Oc|U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NE[1O|M6QCd-MkS2OVc{QTh:L3G+
SK-Hep1 Mm\kRZBweHSxc3nzJGF{e2G7 MVOwMVIxKM7:TR?= NF7YRm01QMLiaB?= MkfhbY5lfWOnczDj[YxtKGGyb4D0c5NqeyCmb4PlJIRmeGWwZHXueIx6 NWL5dGdXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS2OVc{QThpPkK0OlU4Ozl6PD;hQi=>
H1703 MkO4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MY\JR|UxRTBwMEWg{txO MlHhQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5Mkm0NFMoRjJ|N{K5OFA{RC:jPh?=
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Sf9 M2G0emZ2dmO2aX;uJIF{e2G7 NEOycFAzOCCvaX7z MWDJcohq[mm2aX;uJI9nKGi3bXHuJGdUXC2odYPl[EBXTUeIUkKg[ZhxemW|c3XkJIlvKFOoOTDpcpNm[3RiY3XscJMh[W[2ZYKgNlAhdWmwczDifUB{[2mwdHnscIF1cW:wIHPveY51cW6pLDDJR|UxKD1iMD6wNlEh|ryPLh?= M3;o[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6NUW5OVI1Lz5zOEW1PVUzPDxxYU6=
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A673 MXfxTHRUKGG|c3H5 NXHJTFhoeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFG2O|Mh[2WubIO= NF61UVk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
DAOY Ml;ndWhVWyCjc4PhfS=> M2q2SpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCGQV;ZJINmdGy| NFT6dHM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
Saos-2 NEDvS4lyUFSVIHHzd4F6 NVrOfopTeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPhc5MuOiClZXzsdy=> MmrGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
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SK-N-SH NHz6cHdyUFSVIHHzd4F6 M{nrepFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMXNJKGOnbHzz Mlu5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
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OHS-50 Mn:3dWhVWyCjc4PhfS=> M2nYUpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCRSGOtOVAh[2WubIO= NFTkZWg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
LAN-5 NGewUppyUFSVIHHzd4F6 NVXOR3dmeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhVEGQLUWgZ4VtdHN? Mn\LQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
DAOY MkLDdWhVWyCjc4PhfS=> MmrTdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgSGFQYSClZXzsdy=> MoDMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
Rh41 NHToT4VyUFSVIHHzd4F6 NGDFfGtyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUni0NUBk\Wyucx?= M2LsRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
MG 63 (6-TG R) MW\xTHRUKGG|c3H5 MX\xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDNS{A3OyBqNj3US{BTMSClZXzsdy=> NHzWRWo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
Rh30 MV3xTHRUKGG|c3H5 MUXxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDSbFMxKGOnbHzz MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
U-2 OS NWnrWYxQeUiWUzDhd5NigQ>? NWXVT3JreUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhXS1{IF;TJINmdGy| MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
OHS-50 MnnndWhVWyCjc4PhfS=> MYDxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDPTHMuPTBiY3XscJM> MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
Rh41 NU[wfZBneUiWUzDhd5NigQ>? NXL2N5FweUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhWmh2MTDj[Yxtew>? NF[3PYs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
SJ-GBM2 Mk\kdWhVWyCjc4PhfS=> NH\1RpVyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1qtS2JOOiClZXzsdy=> MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
NB-EBc1 MmXUdWhVWyCjc4PhfS=> NGfFc3VyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKtSWJkOSClZXzsdy=> M2LtXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
LAN-5 M4nkPZFJXFNiYYPzZZk> NYXLcY8zeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFzBUk02KGOnbHzz NFTmVIY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
NB1643 Ml;mdWhVWyCjc4PhfS=> M{nDbJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJG5DOTZ2MzDj[Yxtew>? MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
SK-N-MC MYHxTHRUKGG|c3H5 MX;xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDTT{1PNU2FIHPlcIx{ MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
TC32 MUDxTHRUKGG|c3H5 MUPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDUR|MzKGOnbHzz NV\kXVN[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh18 M4CyVZFJXFNiYYPzZZk> M3XsepFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHJpOThiY3XscJM> NFHvR|E9[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
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.

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-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. 

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.

27581340 29934570 26072676
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

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
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Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04976036 Not yet recruiting Drug: Nintedanib|Drug: Placebo Telangiectasia Hereditary Hemorrhagic Dr. Romain Lazor|Boehringer Ingelheim|Centre Hospitalier Universitaire Vaudois September 2021 Phase 2
NCT04971746 Recruiting Drug: Pirfenidone|Drug: GLPG4716|Drug: Nintedanib Healthy Galapagos NV July 19 2021 Phase 1
NCT04888715 Recruiting Drug: DWN12088|Drug: Pirfenidone|Drug: Nintedanib Idiopathic Pulmonary Fibrosis Daewoong Pharmaceutical Co. LTD. July 23 2021 Phase 1
NCT04856111 Recruiting Drug: Pirfenidone|Drug: Nintedanib Novel Coronavirus-induced Lung Fibrosis Postgraduate Institute of Medical Education and Research March 17 2021 Phase 4
NCT04525547 Recruiting Drug: Nintedanib Idiopathic Pulmonary Fibrosis Boehringer Ingelheim January 13 2021 --

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

VEGFR Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID