Neratinib (HKI-272)

For research use only.

Catalog No.S2150

67 publications

Neratinib (HKI-272) Chemical Structure

CAS No. 698387-09-6

Neratinib (HKI-272) is a highly selective HER2 and EGFR inhibitor with IC50 of 59 nM and 92 nM in cell-free assays; weakly inhibits KDR and Src, no significant inhibition to Akt, CDK1/2/4, IKK-2, MK-2, PDK1, c-Raf and c-Met. Phase 3.

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Selleck's Neratinib (HKI-272) has been cited by 67 publications

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Choose Selective HER2 Inhibitors

Biological Activity

Description Neratinib (HKI-272) is a highly selective HER2 and EGFR inhibitor with IC50 of 59 nM and 92 nM in cell-free assays; weakly inhibits KDR and Src, no significant inhibition to Akt, CDK1/2/4, IKK-2, MK-2, PDK1, c-Raf and c-Met. Phase 3.
Targets
HER2 [1]
(Cell-free assay)
EGFR [1]
(Cell-free assay)
KDR [1]
(Cell-free assay)
Src [1]
(Cell-free assay)
59 nM 92 nM 800 nM 1.4 μM
In vitro

Neratinib weakly inhibits tyrosine kinases KDR and Src with IC50 of 0.8 μM and 1.4 μM, respectively, being 14- and 24-fold less active compared with HER2. Neratinib displays no activity against other serine-threonine kinases such as Akt, cyclin D1/cdk4, cyclin E/cdk2, cyclin B1/cdk1, IKK-2, MK-2, PDK1, c-Raf, and Tpl-2, as well as the tyrosine kinase c-Met. Neratinib selectively inhibits the proliferation of 3T3 cells transfected with the HER2 (3T3/neu), as well as two other HER-2-overexpressing SK-Br-3 and BT474 cells with IC50 values of 2-3 nM, displaying >230-fold potency compared with non-transfected 3T3 cells as well as MDA-MB-435 and SW620 which are EGFR- and HER2-negative. Neratinib also inhibits the proliferation of EGFR-dependent A431 cells with an IC50 of 81 nM. Neratinib reduces HER2 receptor autophosphorylation in BT474 cells with an IC50 of 5 nM, and EGF-dependent phosphorylation of EGFR in A431 cells with IC50 of 3 nM. Blocking of HER-2 by Neratinib results in inhibition of downstream MAPK and Akt pathways with IC50 of 2 nM, more potently than Trastuzumab. Neratinib inhibits the cyclin D1 expression and the phosphorylation of the Rb-susceptibility gene production in BT474 cells with IC50 of 9 nM, leading to G1-S arrest and ultimately decreased cell proliferation. [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BT-474 MnfoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Moj0TWM2ODxyLkCwOUDPxE1? MnHIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
EFM-192A NUDkUVA2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEfBWnRKSzVyPECuNFA2KM7:TR?= MnfXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
HCC1569 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXzhS4FuUUN3MEywMlAxPSEQvF2= M3;qeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
HCC1954 NEPEXVBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M13re2lEPTB:MD6wNFUh|ryP MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
MDA-MB-175 MlzNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnjJTWM2ODxyLkCwOUDPxE1? MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
MDA-MB-361 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWjBfJZ5UUN3MEywMlAxPSEQvF2= MkPnQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
SK-BR-3 NYixfXBwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXXJR|UxRDBwMEC1JO69VQ>? NFP4V4c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
UACC-812 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn;kTWM2ODxyLkCwOUDPxE1? NV:wcYJxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
UACC-893 NIfwWFdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoruTWM2ODxyLkCwOUDPxE1? NXTNTHBuRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
SUM-225 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVLJR|UxRTBwMEGg{txO NIDrbGg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
SUM-190 NYXHfYl3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml70TWM2OD1yLkCxJO69VQ>? MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
ZR-75-1 MlPMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlT1TWM2OD1yLkCzJO69VQ>? NGDHc2Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
HCC70 NFHIc5hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXPJR|UxRTBwMEOg{txO MkX2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
BT-20 NGntVWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3jo[2lEPTB;MD6wO{DPxE1? NXroelVGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
MDA-MB-453 NWPQOVlrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUXJR|UxRTBwMEmg{txO MmqwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
HCC1187 MnzXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1:yeGlEPTB;MD6xNEDPxE1? M{DUbVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
EFM-19 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFOzWIZKSzVyPUCuNVEh|ryP M{LmOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
T-47D MnTuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mo\oTWM2OD1yLkG2JO69VQ>? NIrWVHM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
MDA-MB-134 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV\JR|UxRTBwMUeg{txO M1P5UlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
HCC38 NEnMbIhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWPiZW1CUUN3ME2wMlI2KM7:TR?= MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
MDA-MB-435 NWP3bJN2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVvRTXhHUUN3ME2wMlM{KM7:TR?= MmrZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
MDA-MB-468 NHL6TWFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVHIOZl[UUN3ME2wMlM{KM7:TR?= MkfEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
CAMA-1 MoPES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4PPfGlEPTB;MD6zO{DPxE1? NWXZdIJSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
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MCF-7 NVTST48zT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYD0OFlXUUN3ME2wMlQyKM7:TR?= M1WxeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
MDA-MB-415 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NW\tbotPUUN3ME2wMlQzKM7:TR?= MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
HCC1806 NYSyd2g2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUjJR|UxRTBwNESg{txO M{nEV|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
HCC1395 MmL2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV\JR|UxRTBwNEmg{txO NIG1eYs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
HCC1937 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M331V2lEPTB;MD61NEDPxE1? MnWwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
HCC1143 M2DXT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXXJR|UxRTBwNUSg{txO M1flZ|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
UACC-732 NWPQPGJVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWPzcHVHUUN3ME2wMlY2KM7:TR?= NX;6bpdMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
MDA-MB-231 NFfCZohIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYXJR|UxRTFwMECg{txO MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
MDA-MB-157 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NULTbYV6UUN3ME2xMlEzKM7:TR?= NFLUUYM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
BT-549 NIC4bGJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWXJR|UxRTFwMUSg{txO M1LNUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
KPL-1 NVrOOlJZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXfwS|Y2UUN3ME2xMlg6KM7:TR?= NF3SVI49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
CAL-51 NUHMNFJ2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGi1OldKSzVyPUGuPFkh|ryP NHmxOVg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
BT474 NFzqUnhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4rubGlEPTB;MD6wNFMzOyEEsTCwMlAxODd3IN88US=> MmfyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN6MU[yOVQoRjJ|OEG2NlU1RC:jPh?=
SKBR3 NHexepdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYiwbFNtUUN3ME2wMlAxPzViwsGgNE4xODVizszN MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzhzNkK1OEc,OjN6MU[yOVQ9N2F-
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KB MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIrMcHpKSzVyPUSuNVMhyrFiMD60O{DPxE1? MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjR7MUmzOUc,OjJ2OUG5N|U9N2F-
KBv200 M3;5[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{\LfGlEPTB;Nj6wN{DDuSByLk[0JO69VQ>? MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjR7MUmzOUc,OjJ2OUG5N|U9N2F-
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MCF-7/Adr M1vtPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2q4W2lEPTB;IEKuPFghyrFiMD6zNEDPxE1? M17FT|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{NEmxPVM2Lz5{MkS5NVk{PTxxYU6=
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MCF-7/FLV1000 NIi2VmNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX;HZ4E4UUN3ME23MlA6KMLzIECuO|Eh|ryP NFLhTY49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkS5NVk{PSd-MkK0PVE6OzV:L3G+
HL60 M33DU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2LTeWlEPTB;Mj6yOkDDuSByLkKzJO69VQ>? NUDROXl5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0PVE6OzVpPkKyOFkyQTN3PD;hQi=>
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HEK293/pcDNA3.1 NIXBWFlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHW3SYFKSzVyPUWuNlkhyrFiMD61N{DPxE1? MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjR7MUmzOUc,OjJ2OUG5N|U9N2F-
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L858R(EGFR) MkP3R4VtdCCYaXHibYxqfHliQYPzZZk> NVXhfHBv\GWlcnXhd4V{KGOnbHygeoli[mmuaYT5JIlvKHSrbXWgZY5lKGSxc3Wg[IVx\W6mZX70JI1idm6nch?= MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPzNzMUCwNkc,OTd|MUGwNFI9N2F-
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G776insV_G/L MmfIR4VtdCCYaXHibYxqfHliQYPzZZk> Mn76[IVkemWjc3XzJINmdGxidnnhZoltcXS7IHnuJJRqdWViYX7kJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M32xRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5M{GxNFAzLz5zN{OxNVAxOjxxYU6=
P780insGSP NYTlN2xNS2WubDDWbYFjcWyrdImgRZN{[Xl? NHi0OZJl\WO{ZXHz[ZMh[2WubDD2bYFjcWyrdImgbY4hfGmvZTDhcoQh\G:|ZTDk[ZBmdmSnboSgcYFvdmW{ NFfs[oE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{OxNVAxOid-MUezNVExODJ:L3G+
NCI-H1781 M2K5Zmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWfxR2s2cW6qaXLpeJMh[2WubDDndo94fGhiaX6geIlu\SCjbnSg[I9{\SCmZYDlcoRmdnRibXHucoVz MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPjhzOE[xPEc,OTZ6MUi2NVg9N2F-
HCC827 NF6yZZVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlP3bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5idHnt[UBidmRiZH;z[UBl\XCnbnTlcpQhdWGwbnXy M4XzT|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF4OEG4OlE5Lz5zNkixPFYyQDxxYU6=
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A549 M1HhOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWKybXIycW6qaXLpeJMh[2WubDDndo94fGhiaX6geIlu\SCjbnSg[I9{\SCmZYDlcoRmdnRibXHucoVz M3XBVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF4OEG4OlE5Lz5zNkixPFYyQDxxYU6=
3T3 NXq3e29ST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{X2emlEPTB;N{CwJOKyKDd6IH7N MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPTF5M{CwPEc,OTVzN{OwNFg9N2F-
3T3/neu MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUfJR|UxRTNiwsGgNE4yPCCwTR?= MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPTF5M{CwPEc,OTVzN{OwNFg9N2F-
SK-Br-3 NFXNT3NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFvPSHdKSzVyPUKgxtEhOC5zODDuUS=> MlvJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTVzN{OwNFgoRjF3MUezNFA5RC:jPh?=
BT 474 NWDrV4RXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{O3VWlEPTB;MjFCtUAxNjB4IH7N MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPTF5M{CwPEc,OTVzN{OwNFg9N2F-
A431 NX\ERmFtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH[xZm5KSzVyPUixJOKyKDlibl2= NH65WGk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNUG3N|AxQCd-MUWxO|MxODh:L3G+
MDA-MB-435 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVfJR|UxRTl4MDFCtUAyPjVibl2= MoLKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTVzN{OwNFgoRjF3MUezNFA5RC:jPh?=
SW620 M37SOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWDJR|UxRTZ7MDFCtUA5PCCwTR?= M3PlflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF3MUezNFA5Lz5zNUG3N|AxQDxxYU6=
SKBR3 MWfGeY5kfGmxbjDhd5NigQ>? MoezTY5pcWKrdHnvckBw\iCqdX3hckBJ\XJ{IHnuJHNMSlJ|IHPlcIx{NCCHQ{WwJF0hOC5yMEKg{txONg>? MlvXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyN{e0NlUoRjF6MEe3OFI2RC:jPh?=
BT474 NVi1clZjTnWwY4Tpc44h[XO|YYm= NI\xWlNKdmirYnn0bY9vKG:oIHj1cYFvKEinckKgbY4hSlR2N{SgZ4VtdHNuIFXDOVAhRSByLkCwNkDPxE1w NIHYR4U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEC3O|QzPSd-MUiwO|c1OjV:L3G+
A431 MYjGeY5kfGmxbjDhd5NigQ>? NYf1RXJTUW6qaXLpeIlwdiCxZjDoeY1idiCKZYKyJIlvKEF2M{GgZ4VtdHNuIFXDOVAhRSByLkC4NUDPxE1w Mli1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyN{e0NlUoRjF6MEe3OFI2RC:jPh?=
SW620 NYnCbog1TnWwY4Tpc44h[XO|YYm= MnzOTY5pcWKrdHnvckBw\iCqdX3hckBJ\XJ{IHnuJHNYPjJyIHPlcIx{NCCHQ{WwJF0hOC54OTFOwG0v M2TIcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MEe3OFI2Lz5zOEC3O|QzPTxxYU6=
BA/F3 MmDCR5l1d3SxeHnjbZR6KGG|c3H5 M4XPWWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KG2xdYPlJGJCN0Z|IHPlcIx{KGW6cILld5NqdmdiRVfGVkBNQDV6UjDteZRidnRuIFnDOVAhRSByLkCwN|Uh|ryPLh?= NUPYNIV2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUmyN|kzOjlpPkG5NlM6OjJ7PD;hQi=>
BA/F3 MkXGR5l1d3SxeHnjbZR6KGG|c3H5 NWnJXGxYS3m2b4TvfIlkcXS7IHHnZYlve3RibX;1d4UhSkFxRkOgZ4VtdHNiZYjwdoV{e2mwZzDFS2ZTKEx6NUjSM3Q4QTCPIH31eIFvfCxiSVO1NEA:KDBwMUig{txONg>? NV3Xb4VJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUmyN|kzOjlpPkG5NlM6OjJ7PD;hQi=>
Sf9 MXrGeY5kfGmxbjDhd5NigQ>? MXWxNEBucW6| MUnJcohq[mm2aX;uJI9nKGi3bXHuJJdqdGRidInw[UBGT0[UIHX4dJJme3OnZDDpckBU\jliY3XscJMhfXOrbnegX4didW2jM{LQYU1CXFBiYX\0[ZIhOTBibXnud{BjgSC|Y3nueIltdGG2aX;uJINwfW62aX7nMEBKSzVyIE2gNE4xODJ3IN88UU4> MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyME[0N{c,OjR7MEC2OFM9N2F-
Sf9 Mm\CSpVv[3Srb36gZZN{[Xl? NWP4RohzOTBibXnudy=> MY\Jcohq[mm2aX;uJI9nKGi3bXHuJGVITlJiVEe5NG0wVDh3OGKgcZV1[W62IHX4dJJme3OnZDDpckBU\jliY3XscJMhfXOrbnegX4didW2jM{LQYU1CXFBiYX\0[ZIhOTBibXnud{BjgSC|Y3nueIltdGG2aX;uJINwfW62aX7nMEBKSzVyIE2gNE4xPjZizszNMi=> Mn;SQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MEC2OFMoRjJ2OUCwOlQ{RC:jPh?=
BAF3 Ml3SSpVv[3Srb36gZZN{[Xl? NVHyXlR7PzJiaILz MnPhTY5pcWKrdHnvckBw\iCWZXyt[pV{\WRiSVfGNXIhMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5ibX;1d4UhSkGIMzDj[YxteyCjc4Pld5Nm\CCjczDndo94fGhiaX7obYJqfGmxbjDh[pRmeiB5MjDodpMh[nliQ3XscHRqfGW{LVfsc{Bie3OjeTygS2k2OCB;IECuNVkh|ryPLh?= M2TqUlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6MkiyNVIzLz5{OEK4NlEzOjxxYU6=
BAF3 MmrPSpVv[3Srb36gZZN{[Xl? NGTtTGk4OiCqcoO= MUnJcohq[mm2aX;uJI9nKFSnbD3meZNm\CCLTmPSJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW|c3XkJIlvKG2xdYPlJGJCTjNiY3XscJMh[XO|ZYPz[YQh[XNiZ4Lve5RpKGmwaHnibZRqd25iYX\0[ZIhPzJiaILzJIJ6KEOnbHzUbZRmei2JbH:gZZN{[XluIFfJOVAhRSByLkK5JO69VS5? M{H6TVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6MkiyNVIzLz5{OEK4NlEzOjxxYU6=
BAF3 MmDPS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MlrRO|IhcHK| NX76NGw4T3Kxd4ToJIlvcGmkaYTpc44hd2ZibX;1d4UhSkGIMzDj[YxteyCjZoTldkA4OiCqcoOgZpkhS2WubGTpeIVzNUeubzDhd5NigSxiR1m1NEA:KDFwOTFOwG0v NHj5Z5c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEK4NlEzOid-MkiyPFIyOjJ:L3G+

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
pHER2 / HER2 / pAKT / AKT / pERK / ERK ; 

PubMed: 24009064     


BT474 (right) and SKBR3 (left) cell were treated for 1 hour or 1 day with increasing concentrations of neratinib. After lysis, protein levels were assessed using western blotting techniques.

p-ERBB2 / ERBB2 / p-ERBB3 / ERBB3 / p-EGFR / p-90RSK ; 

PubMed: 30118499     


(A) Effects of MEK162 alone, neratinib alone, and the combination of MEK162 plus neratinib were assessed in sensitive, inflammatory subtype cell lines (NCI-H747, SW-837), (B) resistant, stem-like subtype cell lines (SW480, SW620). Cell lines were cultured䲧疝Ỵ疞㧀疜膉痘 瘿삨ՂᾰƌՂĀ 㺣痖帉痖Ѐ瑖堘𢡄빢᎒ՂĀ鑸᎒彿堙奋堙巫堙᎒ﻺ᎒彿堙ﻮ᎒塚堙ﻺ᎒ꍈ堞빢᎒學堙漸堞圔堙빢᎒圞堙圭堙𢡄玚Wᾰƌ ᾰƌ戤瘯Ɖ뙠ෆ䐺痖暼瘿뙠ෆᾰƌ 뙠ෆÐ㺣痖뙠ෆ€𢡄뙤ෆ€䀷痗뙤ෆ౴뙤ෆ㵶痗뙤ෆ뺖᎒泌Itemセ᎒

24009064 30118499
Growth inhibition assay
Cell viability ; 

PubMed: 30118499     


NCI-H747, SW837, SW1116, SW1463, NCI-H508, SNU-C1, SW480, SW620, C2BBE1, Hs675.T, and HCT116 cells were treated with a constant dose of MEK162 (0.5 μM) in combination with different doses of neratinib for 72 hours. Dimethyl sulfoxide (DMSO) (0.01%) was us䲧疝Ỵ疞㧀疜膉痘 瘿삨ՂᾰƌՂĀ 㺣痖帉痖Ѐ瑖堘𢡄빢᎒

30118499
In vivo Oral administration of Neratinib significantly inhibits the growth of 3T3/neu xenografts, with inhibition of 34%, 53%, 98%, and 98% at dose of 10, 20, 40, and 80 mg/kg/day, respectively. Consistent with the inhibition of HER-2 phosphorylation by 84% within 1 hour of administration at 40 mg/kg/day, Neratinib inhibits the growth of BT474 xenografts by 70-82%, 67%, and 93% at dose of 5, 10, and 40 mg/kg/day, respectively. Neratinib is also effective against SK-OV-3 xenografts with inhibition of 31% and 85% at 5 and 60 mg/kg/day, respectively. Neratinib is less potent against EGFR-dependent A431 xenografts than HER-2-dependent tumors, with 32% and 44% inhibition at 5 and 20 mg/kg/day, respectively. Neratinib displays little activity against MCF-7 and MX-1 xenografts expressing low levels of HER-2 and EGFR, with only 28% inhibition at 80 mg/kg/day, suggesting that Neratinib has selective activity for cells expressing HER-2 or EGFR. [1]

Protocol

Kinase Assay:[1]
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Cell-free autophosphorylation assay using time-resolved fluorometry:

Neratinib is prepared as 10 mg/mL stocks in DMSO and diluted in 25 mM HEPES (pH 7.5; 0.002 ng/mL-20 μg/mL). Purified recombinant COOH-terminal fragments of HER2 (amino acids 676-1255) or epidermal growth factor receptor (EGFR) (amino acids 645-1186) [diluted in 100 mM HEPES (pH 7.5) and 50% glycerol] is incubated with increasing concentrations of Neratinib in 4 mM HEPES (pH 7.5), 0.4 mM MnCl2, 20 μM sodium vanadate, and 0.2 mM DTT for 15 minutes at room temperature in 96-well ELISA plates. The kinase reaction is initiated by the addition of 40 μM ATP and 20 mM MgCl2 and allowed to proceed for 1 hour at room temperature. Plates are washed, and phosphorylation is detected using Europium-labeled anti-phospho-tyrosine antibodies (15 ng/well). After washing and enhancement steps, signal is detected using a Victor2 fluorescence reader (excitation wavelength 340 nm, emission wavelength 615 nm). The concentration of Neratinib that inhibits receptor phosphorylation by 50% (IC50) is calculated from inhibition curves.
Cell Research:[1]
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  • Cell lines: 3T3, 3T3/neu, A431, BT474, SK-Br-3, MDA-MB-435, and SW480
  • Concentrations: Dissolved in DMSO, final concentrations 0.5 ng/mL-5 μg/mL
  • Incubation Time: 2 or 6 days
  • Method: Cells are exposed to various concentrations of Neratinib for 2, or 6 days. Cell proliferation is determined using sulforhodamine B, a protein binding dye. Briefly, cells are fixed with 10% trichloroacetic acid and washed extensively with water. Cells are then stained with 0.1% sulforhodamine B and washed in 5% acetic acid. Protein-associated dye is solubilized in 10 mM Tris, and absorbance is measured at 450 nM. The concentration of Neratinib that inhibits cell proliferation by 50% (IC50) is determined from inhibition curves.
    (Only for Reference)
Animal Research:[1]
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  • Animal Models: Female athymic (nude) mice implanted s.c. with 3T3/neu, BT474, MCF-7, or SK-OV-3 cells
  • Dosages: ~80 mg/kg/day
  • Administration: Gavage
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 5 mg/mL warmed (8.97 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
30% PEG400+0.5% Tween80+5% propylene glycol
For best results, use promptly after mixing.
5 mg/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 557.04
Formula

C30H29ClN6O3

CAS No. 698387-09-6
Storage powder
in solvent
Synonyms N/A
Smiles CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)Cl)C#N)NC(=O)C=CCN(C)C

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    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    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
NCT04388384 Recruiting Drug: Neratinib Breast Neoplasm Pierre Fabre Pharma GmbH|iOMEDICO AG|Pierre Fabre Pharma Austria|Pierre Fabre Pharma AG April 20 2020 --
NCT03812393 Recruiting Drug: Neratinib Triple Negative Breast Cancer|Early-stage Breast Cancer|HER2-positive Breast Cancer West Cancer Center|Celcuity|Puma Biotechnology Inc. June 21 2019 Phase 2
NCT03919292 Recruiting Drug: Neratinib|Drug: Divalproex Sodium Solid Tumor Adult Virginia Commonwealth University|Puma Biotechnology Inc. May 1 2019 Phase 1|Phase 2
NCT03786107 Recruiting Diagnostic Test: Almac HER-Seq Assay Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer|Metastatic Cervical Cancer Puma Biotechnology Inc. March 14 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

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

If you have any other enquiries, please leave a message.

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HER2 Signaling Pathway Map

HER2 Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID