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 82 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 M4Xu[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEjTdZZKSzVyPECuNFA2KM7:TR?= NG[0N5g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
EFM-192A NEDEV49Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVzJR|UxRDBwMEC1JO69VQ>? MoHiQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
HCC1569 MlzGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml3uTWM2ODxyLkCwOUDPxE1? NWPU[mlHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
HCC1954 M{fDVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NELybG1KSzVyPECuNFA2KM7:TR?= NF7Qe5E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
MDA-MB-175 NEi2PGRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW\Ve5pDUUN3MEywMlAxPSEQvF2= MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
MDA-MB-361 M3v4cWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXzH[GJUUUN3MEywMlAxPSEQvF2= MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
SK-BR-3 NYjxT45nT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoHOTWM2ODxyLkCwOUDPxE1? NV76W4FpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
UACC-812 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1PHfGlEPTB:MD6wNFUh|ryP M4nKdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
UACC-893 M3jlXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4\nNmlEPTB:MD6wNFUh|ryP NXW3TpBmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
SUM-225 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUTJR|UxRTBwMEGg{txO NYPse|FURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
SUM-190 NEXzOYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX\SfFl{UUN3ME2wMlAyKM7:TR?= M1fqXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
ZR-75-1 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn\oTWM2OD1yLkCzJO69VQ>? NEjmdIg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
HCC70 NUnESXJ[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NILvR3VKSzVyPUCuNFMh|ryP MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
BT-20 Ml;jS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVrJR|UxRTBwMEeg{txO NUTEfpJIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
MDA-MB-453 NIC4VlRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3uwcWlEPTB;MD6wPUDPxE1? Mkm5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
HCC1187 NXzKd|hXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkOxTWM2OD1yLkGwJO69VQ>? Ml3KQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
EFM-19 Mmi0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWDJR|UxRTBwMUGg{txO M4DnZ|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
T-47D NYOzSm9{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2LKS2lEPTB;MD6xOkDPxE1? NXPHfVlDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
MDA-MB-134 NXvINZVVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXr4N5BvUUN3ME2wMlE4KM7:TR?= Mn\NQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
HCC38 NWrvWFhlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{LkPWlEPTB;MD6yOUDPxE1? MnG3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
MDA-MB-435 MlLhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV;QdY5FUUN3ME2wMlM{KM7:TR?= MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
MDA-MB-468 M2qxbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHPRblJKSzVyPUCuN|Mh|ryP M2PUdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
CAMA-1 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEiweXhKSzVyPUCuN|ch|ryP MlfYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
MDA-MB-436 M4\Pd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYDGOYNpUUN3ME2wMlQyKM7:TR?= NFTETYo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
MCF-7 NED0cVhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVzlR3J1UUN3ME2wMlQyKM7:TR?= M4\VUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
MDA-MB-415 NX3HXYdGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn7STWM2OD1yLkSyJO69VQ>? MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
HCC1806 NXTVVVVFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXzoRmlSUUN3ME2wMlQ1KM7:TR?= NHHjb3o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
HCC1395 NYTwO|hbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUXBfpk1UUN3ME2wMlQ6KM7:TR?= MnvuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
HCC1937 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWTJR|UxRTBwNUCg{txO NHz6dY89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
HCC1143 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX7kU3BlUUN3ME2wMlU1KM7:TR?= MnXVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
UACC-732 M{OzZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVXN[I5jUUN3ME2wMlY2KM7:TR?= MluxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
MDA-MB-231 NEnocllIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWW2[VZ[UUN3ME2xMlAxKM7:TR?= MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
MDA-MB-157 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH7lRVJKSzVyPUGuNVIh|ryP MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
BT-549 M1T6dmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{jMXmlEPTB;MT6xOEDPxE1? MkK5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
KPL-1 NIjW[5ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWHJR|UxRTFwOEmg{txO NGfKNJA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
CAL-51 Mn;ES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHvXSY5KSzVyPUGuPFkh|ryP NEfKd4w9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
BT474 Ml23S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV7JR|UxRTBwMECzNlMhyrFiMD6wNFA4PSEQvF2= MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzhzNkK1OEc,OjN6MU[yOVQ9N2F-
SKBR3 M{XEcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFTqN5hKSzVyPUCuNFA4PSEEsTCwMlAxPSEQvF2= NUnrZYNjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO4NVYzPTRpPkKzPFE3OjV2PD;hQi=>
MDAMB453 NYjmfGVST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX7QfJlTUUN3ME2xMlU6KMLzIECuNVc6KM7:TR?= NEnjSHo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{ixOlI2PCd-MkO4NVYzPTR:L3G+
KB NEHEdFVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1\TfGlEPTB;ND6xN{DDuSByLkS3JO69VQ>? NIrRSos9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkS5NVk{PSd-MkK0PVE6OzV:L3G+
KBv200 NGH6[G1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVPJR|UxRTZwMEOgxtEhOC54NDFOwG0> NF3LOZQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkS5NVk{PSd-MkK0PVE6OzV:L3G+
MCF-7 M3zJfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEjZO4ZKSzVyPUOuN|AhyrFiMD60NUDPxE1? NYnwVoZWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0PVE6OzVpPkKyOFkyQTN3PD;hQi=>
MCF-7/Adr NImwWWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEHKcplKSzVyPTCyMlg5KMLzIECuN|Ah|ryP NFrXVpM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkS5NVk{PSd-MkK0PVE6OzV:L3G+
MCF-7 MknhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV\qSHExUUN3ME2zMlAzKMLzIECuN|Qh|ryP NVjJXpVwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0PVE6OzVpPkKyOFkyQTN3PD;hQi=>
MCF-7/FLV1000 NWrGdZRsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3fSOGlEPTB;Nz6wPUDDuSByLkexJO69VQ>? M4i5UVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{NEmxPVM2Lz5{MkS5NVk{PTxxYU6=
HL60 NFS0OHlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmLVTWM2OD1{LkK2JOKyKDBwMkOg{txO NF7wZZg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkS5NVk{PSd-MkK0PVE6OzV:L3G+
HL60/Adr NVWyclR[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIK1e4FKSzVyPUGuOFIhyrFiMD6xOUDPxE1? MnzoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ2OUG5N|UoRjJ{NEmxPVM2RC:jPh?=
HEK293/pcDNA3.1 NITmSWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW[zbpZtUUN3ME21MlI6KMLzIECuOVMh|ryP NXTG[W9QRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0PVE6OzVpPkKyOFkyQTN3PD;hQi=>
HEK293/ABCB1 NFPrZpVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4SzT2lEPTB;Nj65NUDDuSByLkewJEDPxE1? NX63W4NyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0PVE6OzVpPkKyOFkyQTN3PD;hQi=>
SKBR M1XBT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUm1Z2pYOC5yMT2xNFAhdk1? NGTCZZU{NTdiZB?= NFH0TWJqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjD0bY1mKGGwZDDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M3;SdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzNEi3OlA2Lz5{MUS4O|YxPTxxYU6=
L858R(EGFR) MnPTR4VtdCCYaXHibYxqfHliQYPzZZk> MorX[IVkemWjc3XzJINmdGxidnnhZoltcXS7IHnuJJRqdWViYX7kJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M13xNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5M{GxNFAzLz5zN{OxNVAxOjxxYU6=
L858R/T790M(EGFR) MWDD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M4LB[YRm[3KnYYPld{Bk\WyuII\pZYJqdGm2eTDpckB1cW2nIHHu[EBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M3zGflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5M{GxNFAzLz5zN{OxNVAxOjxxYU6=
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NCI-H1781 NYXYZ4VtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUfRd442cW6qaXLpeJMh[2WubDDndo94fGhiaX6geIlu\SCjbnSg[I9{\SCmZYDlcoRmdnRibXHucoVz MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPjhzOE[xPEc,OTZ6MUi2NVg9N2F-
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A549 MnnSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoPObY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5idHnt[UBidmRiZH;z[UBl\XCnbnTlcpQhdWGwbnXy MnPUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTZ6MUi2NVgoRjF4OEG4OlE5RC:jPh?=
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A431 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{XCbGlEPTB;OEGgxtEhQSCwTR?= Mlf5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTVzN{OwNFgoRjF3MUezNFA5RC:jPh?=
MDA-MB-435 M{TreGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlnlTWM2OD17NkCgxtEhOTZ3IH7N NYLySVI1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUWxO|MxODhpPkG1NVc{ODB6PD;hQi=>
SW620 MoTzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2fCUmlEPTB;NkmwJOKyKDh2IH7N NEfrfmk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNUG3N|AxQCd-MUWxO|MxODh:L3G+
SKBR3 MV3GeY5kfGmxbjDhd5NigQ>? NVHLeHRxUW6qaXLpeIlwdiCxZjDoeY1idiCKZYKyJIlvKFONQmKzJINmdGy|LDDFR|UxKD1iMD6wNFIh|ryPLh?= NFiyS3k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEC3O|QzPSd-MUiwO|c1OjV:L3G+
BT474 M{naUmZ2dmO2aX;uJIF{e2G7 NEDB[ZVKdmirYnn0bY9vKG:oIHj1cYFvKEinckKgbY4hSlR2N{SgZ4VtdHNuIFXDOVAhRSByLkCwNkDPxE1w NVrEWZp7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUiwO|c1OjVpPkG4NFc4PDJ3PD;hQi=>
A431 MUDGeY5kfGmxbjDhd5NigQ>? M1iyOWlvcGmkaYTpc44hd2ZiaIXtZY4hUGW{MjDpckBCPDNzIHPlcIx{NCCHQ{WwJF0hOC5yOEGg{txONg>? MljqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyN{e0NlUoRjF6MEe3OFI2RC:jPh?=
SW620 NFnwN2NHfW6ldHnvckBie3OjeR?= MV;Jcohq[mm2aX;uJI9nKGi3bXHuJGhmejJiaX6gV3c3OjBiY3XscJMtKEWFNUCgQUAxNjZ7IN88UU4> Mlz4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyN{e0NlUoRjF6MEe3OFI2RC:jPh?=
BA/F3 NWP5[5RwS3m2b4TvfIlkcXS7IHHzd4F6 MV7DfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRU9HOyClZXzsd{BmgHC{ZYPzbY5oKEWJRmKgUFg2QFJibYX0ZY51NCCLQ{WwJF0hOC5yMEO1JO69VS5? NVfleJZ6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUmyN|kzOjlpPkG5NlM6OjJ7PD;hQi=>
BA/F3 MXrDfZRwfG:6aXPpeJkh[XO|YYm= NYjYNJhwS3m2b4TvfIlkcXS7IHHnZYlve3RibX;1d4UhSkFxRkOgZ4VtdHNiZYjwdoV{e2mwZzDFS2ZTKEx6NUjSM3Q4QTCPIH31eIFvfCxiSVO1NEA:KDBwMUig{txONg>? M2jYblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7MkO5NlI6Lz5zOUKzPVIzQTxxYU6=
Sf9 NUKy[pd5TnWwY4Tpc44h[XO|YYm= NX7wd|V6OTBibXnudy=> MUnJcohq[mm2aX;uJI9nKGi3bXHuJJdqdGRidInw[UBGT0[UIHX4dJJme3OnZDDpckBU\jliY3XscJMhfXOrbnegX4didW2jM{LQYU1CXFBiYX\0[ZIhOTBibXnud{BjgSC|Y3nueIltdGG2aX;uJINwfW62aX7nMEBKSzVyIE2gNE4xODJ3IN88UU4> NGXjUXE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwNFY1Oyd-MkS5NFA3PDN:L3G+
Sf9 NXPWRXozTnWwY4Tpc44h[XO|YYm= NVPIN4JnOTBibXnudy=> M2jZcWlvcGmkaYTpc44hd2ZiaIXtZY4hTUeIUjDUO|kxVS:OOEW4VkBufXSjboSg[ZhxemW|c3XkJIlvKFOoOTDj[YxteyC3c3nu[{Bc\2GvbXGzNnBeNUGWUDDh[pRmeiBzMDDtbY5{KGK7IIPjbY51cWyuYYTpc44h[2:3boTpcoctKEmFNUCgQUAxNjB4NjFOwG0v M3\QfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUCwOlQ{Lz5{NEmwNFY1OzxxYU6=
BAF3 MoT4SpVv[3Srb36gZZN{[Xl? MmDyO|IhcHK| NEHkRm1KdmirYnn0bY9vKG:oIGTlcE1nfXOnZDDJS2YyWiBqdX7rco94diCxcnnnbY4qKGW6cILld5Nm\CCrbjDtc5V{\SCEQV[zJINmdGy|IHHzd4V{e2WmIHHzJIdzd3e2aDDpcohq[mm2aX;uJIFnfGW{IEeyJIhzeyCkeTDD[YxtXGm2ZYKtS4xwKGG|c3H5MEBIUTVyIE2gNE4yQSEQvF2u MoPiQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh{OEKxNlIoRjJ6MkiyNVIzRC:jPh?=
BAF3 M1T2VmZ2dmO2aX;uJIF{e2G7 M4rzVlczKGi{cx?= MXLJcohq[mm2aX;uJI9nKFSnbD3meZNm\CCLTmPSJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW|c3XkJIlvKG2xdYPlJGJCTjNiY3XscJMh[XO|ZYPz[YQh[XNiZ4Lve5RpKGmwaHnibZRqd25iYX\0[ZIhPzJiaILzJIJ6KEOnbHzUbZRmei2JbH:gZZN{[XluIFfJOVAhRSByLkK5JO69VS5? NWe1Z|ZpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkiyPFIyOjJpPkK4NlgzOTJ{PD;hQi=>
BAF3 MUjHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NXK4OXNZPzJiaILz NXrXVZZGT3Kxd4ToJIlvcGmkaYTpc44hd2ZibX;1d4UhSkGIMzDj[YxteyCjZoTldkA4OiCqcoOgZpkhS2WubGTpeIVzNUeubzDhd5NigSxiR1m1NEA:KDFwOTFOwG0v NFPLSnQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEK4NlEzOid-MkiyPFIyOjJ:L3G+
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

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

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
NCT04856475 Withdrawn Drug: Neratinib Breast Cancer|Brain Metastases Jules Bordet Institute November 24 2021 Phase 2
NCT04781374 Recruiting 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
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 Inc.|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

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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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