Neratinib (HKI-272)

Catalog No.S2150

For research use only.

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.

Neratinib (HKI-272) Chemical Structure

CAS No. 698387-09-6

Selleck's Neratinib (HKI-272) has been cited by 85 publications

Purity & Quality Control

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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 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4TYeGlEPTB:MD6wNFUh|ryP NVi5VG1tRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
EFM-192A M3HZWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3W1TWlEPTB:MD6wNFUh|ryP M{jDflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
HCC1569 NUjPWZYxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXPW[mYzUUN3MEywMlAxPSEQvF2= NFPleWo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
HCC1954 M3nnOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWH2XZNtUUN3MEywMlAxPSEQvF2= M{jsZ|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
MDA-MB-175 MkPCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWGzd4ZQUUN3MEywMlAxPSEQvF2= MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
MDA-MB-361 MkC1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUf0WVV6UUN3MEywMlAxPSEQvF2= MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
SK-BR-3 M2G3TWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoTHTWM2ODxyLkCwOUDPxE1? MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
UACC-812 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3LpWmlEPTB:MD6wNFUh|ryP MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
UACC-893 MlHjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3W1PGlEPTB:MD6wNFUh|ryP NGnUSm49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
SUM-225 NXzNeZpZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn;MTWM2OD1yLkCxJO69VQ>? NGDvdlE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
SUM-190 MkDRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlLOTWM2OD1yLkCxJO69VQ>? NYjzclFSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
ZR-75-1 NGXSSHdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF3seIpKSzVyPUCuNFMh|ryP NWPzfZZpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
HCC70 MkTzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVnJR|UxRTBwMEOg{txO NEnkT5I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
BT-20 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHfmU|BKSzVyPUCuNFch|ryP NHX5TFY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
MDA-MB-453 NWDyUGoyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mme1TWM2OD1yLkC5JO69VQ>? NGXYR|I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
HCC1187 M2XueGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHrZVG9KSzVyPUCuNVAh|ryP MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
EFM-19 MoqxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MojVTWM2OD1yLkGxJO69VQ>? MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
T-47D MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlrkTWM2OD1yLkG2JO69VQ>? NVv6bXhKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
MDA-MB-134 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn3ZTWM2OD1yLkG3JO69VQ>? NUTHTXdqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
HCC38 NFrqNlZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUHJR|UxRTBwMkWg{txO NEnhZok9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
MDA-MB-435 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkfmTWM2OD1yLkOzJO69VQ>? NFH0VWg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
MDA-MB-468 MlPVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF\pXphKSzVyPUCuN|Mh|ryP NGHybXM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
CAMA-1 MlOyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2q3TmlEPTB;MD6zO{DPxE1? Mly5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
MDA-MB-436 NV;4XWhPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH7Vb3RKSzVyPUCuOFEh|ryP NGnjV289[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
MCF-7 MnPxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUT4W5FwUUN3ME2wMlQyKM7:TR?= NF\VdpY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
MDA-MB-415 M1nyd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnT3TWM2OD1yLkSyJO69VQ>? NUDVSnU5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
HCC1806 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGTSTXdKSzVyPUCuOFQh|ryP M1XkeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
HCC1395 M1rBfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWfJR|UxRTBwNEmg{txO MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
HCC1937 MkXZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3Po[GlEPTB;MD61NEDPxE1? MknSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
HCC1143 MkHnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX\QTo8{UUN3ME2wMlU1KM7:TR?= NHfzPWk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
UACC-732 M3vaXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MU\JR|UxRTBwNkWg{txO NYnCWGJ2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
MDA-MB-231 M{P4TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mom5TWM2OD1zLkCwJO69VQ>? NGfRVGc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
MDA-MB-157 M33MUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWjOO29HUUN3ME2xMlEzKM7:TR?= NWjMNpBFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
BT-549 MnTTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHzJRVNKSzVyPUGuNVQh|ryP NYL1NIpzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
KPL-1 NXPrcnR7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4XOXmlEPTB;MT64PUDPxE1? MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
CAL-51 NYjvPVhyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWrpN4xlUUN3ME2xMlg6KM7:TR?= NU\3NHBIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
BT474 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFL4eINKSzVyPUCuNFA{OjNiwsGgNE4xODB5NTFOwG0> NXr6dWVxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO4NVYzPTRpPkKzPFE3OjV2PD;hQi=>
SKBR3 Mk\FS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH2zN|ZKSzVyPUCuNFA4PSEEsTCwMlAxPSEQvF2= MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzhzNkK1OEc,OjN6MU[yOVQ9N2F-
MDAMB453 NULxdYNGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NY\DZpdiUUN3ME2xMlU6KMLzIECuNVc6KM7:TR?= NXrRO3lbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO4NVYzPTRpPkKzPFE3OjV2PD;hQi=>
KB MnHIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml2wTWM2OD12LkGzJOKyKDBwNEeg{txO NYTlTo1mRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0PVE6OzVpPkKyOFkyQTN3PD;hQi=>
KBv200 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWXzNGFUUUN3ME22MlA{KMLzIECuOlQh|ryP MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjR7MUmzOUc,OjJ2OUG5N|U9N2F-
MCF-7 M{LodWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHnBbXdKSzVyPUOuN|AhyrFiMD60NUDPxE1? NVHBOmM1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0PVE6OzVpPkKyOFkyQTN3PD;hQi=>
MCF-7/Adr M3:0Xmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF24ZphKSzVyPTCyMlg5KMLzIECuN|Ah|ryP M1zxfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{NEmxPVM2Lz5{MkS5NVk{PTxxYU6=
MCF-7 Mn:0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGjrV41KSzVyPUOuNFIhyrFiMD6zOEDPxE1? MmGyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ2OUG5N|UoRjJ{NEmxPVM2RC:jPh?=
MCF-7/FLV1000 MoDpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYTJR|UxRTdwMEmgxtEhOC55MTFOwG0> NWflTVNyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0PVE6OzVpPkKyOFkyQTN3PD;hQi=>
HL60 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV\wd3ROUUN3ME2yMlI3KMLzIECuNlMh|ryP NGfhXZg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkS5NVk{PSd-MkK0PVE6OzV:L3G+
HL60/Adr M37hOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlLDTWM2OD1zLkSyJOKyKDBwMUWg{txO Mn3DQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ2OUG5N|UoRjJ{NEmxPVM2RC:jPh?=
HEK293/pcDNA3.1 NWTNeotzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUXkbmZbUUN3ME21MlI6KMLzIECuOVMh|ryP MnrrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ2OUG5N|UoRjJ{NEmxPVM2RC:jPh?=
HEK293/ABCB1 NGX1dXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGTDSJRKSzVyPU[uPVEhyrFiMD63NEAh|ryP NFfIXlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkS5NVk{PSd-MkK0PVE6OzV:L3G+
SKBR MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mo\4NE4xOS1zMECgcm0> NHnoR40{NTdiZB?= NF6zPIVqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjD0bY1mKGGwZDDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M4[0O|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzNEi3OlA2Lz5{MUS4O|YxPTxxYU6=
L858R(EGFR) M37GNWNmdGxiVnnhZoltcXS7IFHzd4F6 MYnk[YNz\WG|ZYOgZ4VtdCC4aXHibYxqfHliaX6geIlu\SCjbnSg[I9{\SCmZYDlcoRmdnRibXHucoVz NIH3UlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{OxNVAxOid-MUezNVExODJ:L3G+
L858R/T790M(EGFR) MkPXR4VtdCCYaXHibYxqfHliQYPzZZk> MkGw[IVkemWjc3XzJINmdGxidnnhZoltcXS7IHnuJJRqdWViYX7kJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MnztQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTd|MUGwNFIoRjF5M{GxNFAzRC:jPh?=
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wild-type M3Ho[mNmdGxiVnnhZoltcXS7IFHzd4F6 Mmj1[IVkemWjc3XzJINmdGxidnnhZoltcXS7IHnuJJRqdWViYX7kJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPzNzMUCwNkc,OTd|MUGwNFI9N2F-
A775insYVMA MXvD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NHfTb2ll\WO{ZXHz[ZMh[2WubDD2bYFjcWyrdImgbY4hfGmvZTDhcoQh\G:|ZTDk[ZBmdmSnboSgcYFvdmW{ M1fyWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5M{GxNFAzLz5zN{OxNVAxOjxxYU6=
G776insV_G/L MUjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NI\H[Zhl\WO{ZXHz[ZMh[2WubDD2bYFjcWyrdImgbY4hfGmvZTDhcoQh\G:|ZTDk[ZBmdmSnboSgcYFvdmW{ MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPzNzMUCwNkc,OTd|MUGwNFI9N2F-
P780insGSP M1T4UWNmdGxiVnnhZoltcXS7IFHzd4F6 M3;xOIRm[3KnYYPld{Bk\WyuII\pZYJqdGm2eTDpckB1cW2nIHHu[EBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NE\3Uok9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{OxNVAxOid-MUezNVExODJ:L3G+
NCI-H1781 Ml2yS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXWwPZp3cW6qaXLpeJMh[2WubDDndo94fGhiaX6geIlu\SCjbnSg[I9{\SCmZYDlcoRmdnRibXHucoVz MnfMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTZ6MUi2NVgoRjF4OEG4OlE5RC:jPh?=
HCC827 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmDxbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5idHnt[UBidmRiZH;z[UBl\XCnbnTlcpQhdWGwbnXy MljuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTZ6MUi2NVgoRjF4OEG4OlE5RC:jPh?=
H3255 M4LkNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVLpcohq[mm2czDj[YxtKGe{b4f0bEBqdiC2aX3lJIFv\CCmb4PlJIRmeGWwZHXueEBu[W6wZYK= MnW2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTZ6MUi2NVgoRjF4OEG4OlE5RC:jPh?=
NCI-H1975 NYDKVGxDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2HwcIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIITpcYUh[W6mIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPjhzOE[xPEc,OTZ6MUi2NVg9N2F-
A549 MnLUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV\pcohq[mm2czDj[YxtKGe{b4f0bEBqdiC2aX3lJIFv\CCmb4PlJIRmeGWwZHXueEBu[W6wZYK= Mly5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTZ6MUi2NVgoRjF4OEG4OlE5RC:jPh?=
3T3 NUT2VGU6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYPJR|UxRTdyMDFCtUA4QCCwTR?= Mm\nQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTVzN{OwNFgoRjF3MUezNFA5RC:jPh?=
3T3/neu NF3Kem1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4nFfWlEPTB;MzFCtUAxNjF2IH7N NVL5bpIzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUWxO|MxODhpPkG1NVc{ODB6PD;hQi=>
SK-Br-3 NGTUfG1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnydFhKSzVyPUKgxtEhOC5zODDuUS=> MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPTF5M{CwPEc,OTVzN{OwNFg9N2F-
BT 474 NUexUpB2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkjTTWM2OD1{INMxJFAvODZibl2= NVzVTlNKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUWxO|MxODhpPkG1NVc{ODB6PD;hQi=>
A431 NGfpRWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mo\5TWM2OD16MTFCtUA6KG6P NF7Wb4I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNUG3N|AxQCd-MUWxO|MxODh:L3G+
MDA-MB-435 Ml24S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHLweVVKSzVyPUm2NEDDuSBzNkWgcm0> NIHpSmk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNUG3N|AxQCd-MUWxO|MxODh:L3G+
SW620 MluxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M17S[mlEPTB;NkmwJOKyKDh2IH7N M1nZV|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF3MUezNFA5Lz5zNUG3N|AxQDxxYU6=
SKBR3 NGHOWndHfW6ldHnvckBie3OjeR?= NH;WcW5KdmirYnn0bY9vKG:oIHj1cYFvKEinckKgbY4hW0uEUkOgZ4VtdHNuIFXDOVAhRSByLkCwNkDPxE1w M4\re|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MEe3OFI2Lz5zOEC3O|QzPTxxYU6=
BT474 NHfWNnpHfW6ldHnvckBie3OjeR?= M4XMemlvcGmkaYTpc44hd2ZiaIXtZY4hUGW{MjDpckBDXDR5NDDj[YxteyxiRVO1NEA:KDBwMECyJO69VS5? M1vHelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MEe3OFI2Lz5zOEC3O|QzPTxxYU6=
A431 M3njcGZ2dmO2aX;uJIF{e2G7 NVToXYtqUW6qaXLpeIlwdiCxZjDoeY1idiCKZYKyJIlvKEF2M{GgZ4VtdHNuIFXDOVAhRSByLkC4NUDPxE1w NXnudmk2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUiwO|c1OjVpPkG4NFc4PDJ3PD;hQi=>
SW620 NIfWSHhHfW6ldHnvckBie3OjeR?= MlPCTY5pcWKrdHnvckBw\iCqdX3hckBJ\XJ{IHnuJHNYPjJyIHPlcIx{NCCHQ{WwJF0hOC54OTFOwG0v NHe1SmQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEC3O|QzPSd-MUiwO|c1OjV:L3G+
BA/F3 NIrpW4JEgXSxdH;4bYNqfHliYYPzZZk> MlHQR5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmEwTjNiY3XscJMh\XiycnXzd4lv\yCHR1\SJGw5PTiUIH31eIFvfCxiSVO1NEA:KDBwMECzOUDPxE1w NHPyNVQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUKzPVIzQSd-MUmyN|kzOjl:L3G+
BA/F3 NVj4[ZNWS3m2b4TvfIlkcXS7IHHzd4F6 MkTIR5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmEwTjNiY3XscJMh\XiycnXzd4lv\yCHR1\SJGw5PTiUL2S3PVBOKG23dHHueEwhUUN3MDC9JFAvOThizszNMi=> M1\1flxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7MkO5NlI6Lz5zOUKzPVIzQTxxYU6=
Sf9 NV[zfJBMTnWwY4Tpc44h[XO|YYm= M1zudFExKG2rboO= MoXwTY5pcWKrdHnvckBw\iCqdX3hckB4cWymIIT5dIUhTUeIUjDlfJBz\XO|ZXSgbY4hW2Z7IHPlcIx{KHW|aX7nJHto[W2vYUOyVH0uSVSSIHHmeIVzKDFyIH3pcpMh[nlic3PpcpRqdGyjdHnvckBkd3WwdHnu[{whUUN3MDC9JFAvODB{NTFOwG0v MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyME[0N{c,OjR7MEC2OFM9N2F-
Sf9 Mki3SpVv[3Srb36gZZN{[Xl? NF\RdHMyOCCvaX7z NH33ZWFKdmirYnn0bY9vKG:oIHj1cYFvKEWJRmKgWFc6OE1xTEi1PHIhdXW2YX70JIV5eHKnc4Pl[EBqdiCVZkmgZ4VtdHNidYPpcochY2ejbX3hN|JRZS2DVGCgZYZ1\XJiMUCgcYlveyCkeTDzZ4lvfGmubHH0bY9vKGOxdX70bY5oNCCLQ{WwJF0hOC5yNk[g{txONg>? M{e1W|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUCwOlQ{Lz5{NEmwNFY1OzxxYU6=
BAF3 MVvGeY5kfGmxbjDhd5NigQ>? M1z3N|czKGi{cx?= M{Xh[2lvcGmkaYTpc44hd2ZiVHXsMYZ2e2WmIFnHSlFTKCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIH3veZNmKEKDRkOgZ4VtdHNiYYPz[ZN{\WRiYYOg[5Jwf3SqIHnubIljcXSrb36gZYZ1\XJiN{KgbJJ{KGK7IFPlcIxVcXSncj3HcI8h[XO|YYmsJGdKPTBiPTCwMlE6KM7:TT6= NHTtUmQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEK4NlEzOid-MkiyPFIyOjJ:L3G+
BAF3 MVzGeY5kfGmxbjDhd5NigQ>? NXX2ZmZUPzJiaILz MnfOTY5pcWKrdHnvckBw\iCWZXyt[pV{\WRiSV7TVkApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCvb4Xz[UBDSUZ|IHPlcIx{KGG|c3Xzd4VlKGG|IHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDd{IHjyd{BjgSCFZXzsWIl1\XJvR3zvJIF{e2G7LDDHTVUxKD1iMD6yPUDPxE1w NF3XWVM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEK4NlEzOid-MkiyPFIyOjJ:L3G+
BAF3 NFHaW2ZIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NHf3XXo4OiCqcoO= MV7Hdo94fGhiaX7obYJqfGmxbjDv[kBud3W|ZTDCRWY{KGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDD[YxtXGm2ZYKtS4xwKGG|c3H5MEBIUTVyIE2gNU46KM7:TT6= M1nxblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6MkiyNVIzLz5{OEK4NlEzOjxxYU6=
Assay
Methods Test Index PMID
Western blot pHER2 / HER2 / pAKT / AKT / pERK / ERK ; p-ERBB2 / ERBB2 / p-ERBB3 / ERBB3 / p-EGFR / p-90RSK 24009064 30118499
Growth inhibition assay Cell viability 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 (from reference)

Kinase Assay:[1]
  • 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]
  • 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.
Animal Research:[1]
  • 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

Solubility (25°C)

In vitro

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

Chemical Information

Molecular Weight 557.04
Formula

C30H29ClN6O3

CAS No. 698387-09-6
Storage 3 years -20°C powder
2 years -80°C in solvent
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

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
NCT05388149 Not yet recruiting Drug: Neratinib Breast Cancer|HER2-positive Breast Cancer University Health Network Toronto July 2022 Phase 2
NCT05252988 Not yet recruiting Drug: Neratinib|Drug: Loperamide|Drug: Colesevelam Early-stage Breast Cancer|HER2 Positive Breast Cancer|Hormone Receptor Positive Spanish Breast Cancer Research Group|Puma Biotechnology Inc.|Pierre Fabre Laboratories July 2022 Phase 2
NCT04856475 Withdrawn Drug: Neratinib Breast Cancer|Brain Metastases Jules Bordet Institute November 24 2021 Phase 2
NCT04781374 Terminated Drug: Neratinib Metastatic Prostate Adenocarcinoma|Castration-resistant Prostate Cancer|Prostate Cancer|Prostate Cancer Metastatic Dana-Farber Cancer Institute|Puma Biotechnology Inc. May 21 2021 Phase 2

(data from https://clinicaltrials.gov, updated on 2022-08-01)

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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