Neratinib (HKI-272)

For research use only.

Catalog No.S2150

72 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.

Selleck's Neratinib (HKI-272) has been cited by 72 publications

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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 NYXBNWdrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUHsS4NVUUN3MEywMlAxPSEQvF2= NWexWVA{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
EFM-192A M4[0bmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1ywemlEPTB:MD6wNFUh|ryP M3vCNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
HCC1569 NFvO[pdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1X2WWlEPTB:MD6wNFUh|ryP NU\JTFBMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
HCC1954 M{nwUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWj3b4tYUUN3MEywMlAxPSEQvF2= Mmm1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
MDA-MB-175 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYPjfHlEUUN3MEywMlAxPSEQvF2= MnTLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
MDA-MB-361 MkO5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoTjTWM2ODxyLkCwOUDPxE1? MmfOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
SK-BR-3 NGHKRVZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NILWcWxKSzVyPECuNFA2KM7:TR?= NWnDd2VYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
UACC-812 M2ThW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX;jWIE2UUN3MEywMlAxPSEQvF2= MofQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
UACC-893 MlqzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV;2UGZvUUN3MEywMlAxPSEQvF2= MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
SUM-225 NVHn[GtIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NILwbWtKSzVyPUCuNFEh|ryP M{\2TVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
SUM-190 M3nVfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX7JR|UxRTBwMEGg{txO Mn;ZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
ZR-75-1 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkfyTWM2OD1yLkCzJO69VQ>? M3v2eFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
HCC70 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWrJR|UxRTBwMEOg{txO MnXCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
BT-20 Moe4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3vFbmlEPTB;MD6wO{DPxE1? M1TkN|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
MDA-MB-453 NYO3SHNYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF7QPZZKSzVyPUCuNFkh|ryP NXrxbWY4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
HCC1187 M4jV[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYLJR|UxRTBwMUCg{txO MlGxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
EFM-19 NEjVbZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVvJR|UxRTBwMUGg{txO NI[zcGY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
T-47D M2jUSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGHHU4hKSzVyPUCuNVYh|ryP NXHCWmE1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
MDA-MB-134 NU\Fbpo4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{T2VmlEPTB;MD6xO{DPxE1? NVnkXWVNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
HCC38 M2TIdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYDJR|UxRTBwMkWg{txO NIDQNog9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
MDA-MB-435 NFXvfnVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYDUNmNlUUN3ME2wMlM{KM7:TR?= MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
MDA-MB-468 MkC3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF24c5RKSzVyPUCuN|Mh|ryP M3rRWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
CAMA-1 MkHtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml\zTWM2OD1yLkO3JO69VQ>? Moj4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
MDA-MB-436 NFPWdZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{TYZ2lEPTB;MD60NUDPxE1? MkT2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
MCF-7 NGXJRWlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXjJR|UxRTBwNEGg{txO MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
MDA-MB-415 NY\FTmN5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1zJS2lEPTB;MD60NkDPxE1? MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
HCC1806 M4jIOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M135c2lEPTB;MD60OEDPxE1? MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDByOUC2OEc,OjRyMEmwOlQ9N2F-
HCC1395 NHPVV3VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX\JR|UxRTBwNEmg{txO NV\QXlg3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNFkxPjRpPkK0NFA6ODZ2PD;hQi=>
HCC1937 NX6yc3BWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4\1PWlEPTB;MD61NEDPxE1? NIXiepU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
HCC1143 NYjDfIpxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXHJR|UxRTBwNUSg{txO MoPUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
UACC-732 NVPzO3k3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHq1SlFKSzVyPUCuOlUh|ryP M2HWVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
MDA-MB-231 NVP5cYhzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVjJR|UxRTFwMECg{txO MlrVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
MDA-MB-157 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIDwUItKSzVyPUGuNVIh|ryP M3LSO|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
BT-549 NIqzSHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M17yW2lEPTB;MT6xOEDPxE1? M3i5blxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEC5NFY1Lz5{NECwPVA3PDxxYU6=
KPL-1 NXLCWZZFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1rPc2lEPTB;MT64PUDPxE1? NHfKUYU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECwPVA3PCd-MkSwNFkxPjR:L3G+
CAL-51 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVfJR|UxRTFwOEmg{txO Mn3xQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMEmwOlQoRjJ2MEC5NFY1RC:jPh?=
BT474 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV;3N4xnUUN3ME2wMlAxOzJ|INMxJFAvODByN{Wg{txO MoXrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN6MU[yOVQoRjJ|OEG2NlU1RC:jPh?=
SKBR3 M3S0Xmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnvpTWM2OD1yLkCwO|UhyrFiMD6wNFUh|ryP M17lSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|OEG2NlU1Lz5{M{ixOlI2PDxxYU6=
MDAMB453 MkS0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVnYNHBsUUN3ME2xMlU6KMLzIECuNVc6KM7:TR?= M121dVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|OEG2NlU1Lz5{M{ixOlI2PDxxYU6=
KB NVLCUIltT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2HjPGlEPTB;ND6xN{DDuSByLkS3JO69VQ>? MnXtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ2OUG5N|UoRjJ{NEmxPVM2RC:jPh?=
KBv200 MmDoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVHJR|UxRTZwMEOgxtEhOC54NDFOwG0> MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjR7MUmzOUc,OjJ2OUG5N|U9N2F-
MCF-7 NWrJXZJ6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M365RmlEPTB;Mz6zNEDDuSByLkSxJO69VQ>? MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjR7MUmzOUc,OjJ2OUG5N|U9N2F-
MCF-7/Adr NXzEeJpWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NG\XeodKSzVyPTCyMlg5KMLzIECuN|Ah|ryP NXnOXVcxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0PVE6OzVpPkKyOFkyQTN3PD;hQi=>
MCF-7 MnLOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mln4TWM2OD1|LkCyJOKyKDBwM{Sg{txO Mny1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ2OUG5N|UoRjJ{NEmxPVM2RC:jPh?=
MCF-7/FLV1000 Mne2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4jaSWlEPTB;Nz6wPUDDuSByLkexJO69VQ>? MoS3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ2OUG5N|UoRjJ{NEmxPVM2RC:jPh?=
HL60 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX3jcmExUUN3ME2yMlI3KMLzIECuNlMh|ryP Mlq2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ2OUG5N|UoRjJ{NEmxPVM2RC:jPh?=
HL60/Adr MkC1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF:1ZmxKSzVyPUGuOFIhyrFiMD6xOUDPxE1? NIPST4s9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkS5NVk{PSd-MkK0PVE6OzV:L3G+
HEK293/pcDNA3.1 NEDYXlZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIjIZYpKSzVyPUWuNlkhyrFiMD61N{DPxE1? M1TB[|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{NEmxPVM2Lz5{MkS5NVk{PTxxYU6=
HEK293/ABCB1 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX7GTWszUUN3ME22MlkyKMLzIECuO|AhKM7:TR?= M3PwbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{NEmxPVM2Lz5{MkS5NVk{PTxxYU6=
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L858R(EGFR) M{DifWNmdGxiVnnhZoltcXS7IFHzd4F6 M1zaT4Rm[3KnYYPld{Bk\WyuII\pZYJqdGm2eTDpckB1cW2nIHHu[EBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M{nKXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5M{GxNFAzLz5zN{OxNVAxOjxxYU6=
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P780insGSP NXL1bo91S2WubDDWbYFjcWyrdImgRZN{[Xl? M4j1[4Rm[3KnYYPld{Bk\WyuII\pZYJqdGm2eTDpckB1cW2nIHHu[EBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NHvufXQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{OxNVAxOid-MUezNVExODJ:L3G+
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A549 Mn;1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWXpcohq[mm2czDj[YxtKGe{b4f0bEBqdiC2aX3lJIFv\CCmb4PlJIRmeGWwZHXueEBu[W6wZYK= NHLldXM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNkixPFYyQCd-MU[4NVg3OTh:L3G+
3T3 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVPUZYI{UUN3ME23NFAhyrFiN{igcm0> MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPTF5M{CwPEc,OTVzN{OwNFg9N2F-
3T3/neu MlzUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUjJR|UxRTNiwsGgNE4yPCCwTR?= NGLFXlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNUG3N|AxQCd-MUWxO|MxODh:L3G+
SK-Br-3 NHSwSnNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmfWTWM2OD1{INMxJFAvOThibl2= NF;BNY09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNUG3N|AxQCd-MUWxO|MxODh:L3G+
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A431 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MorYTWM2OD16MTFCtUA6KG6P M1HMNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF3MUezNFA5Lz5zNUG3N|AxQDxxYU6=
MDA-MB-435 Mm\OS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEjBT4RKSzVyPUm2NEDDuSBzNkWgcm0> MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPTF5M{CwPEc,OTVzN{OwNFg9N2F-
SW620 NG\VOWFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX;pN443UUN3ME22PVAhyrFiOESgcm0> NFntXWY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNUG3N|AxQCd-MUWxO|MxODh:L3G+
SKBR3 M2OxZ2Z2dmO2aX;uJIF{e2G7 MUHJcohq[mm2aX;uJI9nKGi3bXHuJGhmejJiaX6gV2tDWjNiY3XscJMtKEWFNUCgQUAxNjByMjFOwG0v NIrGXJk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEC3O|QzPSd-MUiwO|c1OjV:L3G+
BT474 MmHISpVv[3Srb36gZZN{[Xl? MWjJcohq[mm2aX;uJI9nKGi3bXHuJGhmejJiaX6gRnQ1PzRiY3XscJMtKEWFNUCgQUAxNjByMjFOwG0v MmSzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyN{e0NlUoRjF6MEe3OFI2RC:jPh?=
A431 M4G3dWZ2dmO2aX;uJIF{e2G7 M4fFfmlvcGmkaYTpc44hd2ZiaIXtZY4hUGW{MjDpckBCPDNzIHPlcIx{NCCHQ{WwJF0hOC5yOEGg{txONg>? M3HEVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MEe3OFI2Lz5zOEC3O|QzPTxxYU6=
SW620 M2jwXmZ2dmO2aX;uJIF{e2G7 M2TEPWlvcGmkaYTpc44hd2ZiaIXtZY4hUGW{MjDpckBUXzZ{MDDj[YxteyxiRVO1NEA:KDBwNkmg{txONg>? Moj0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyN{e0NlUoRjF6MEe3OFI2RC:jPh?=
BA/F3 M3XXO2N6fG:2b4jpZ4l1gSCjc4PhfS=> M1vlZmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KG2xdYPlJGJCN0Z|IHPlcIx{KGW6cILld5NqdmdiRVfGVkBNQDV6UjDteZRidnRuIFnDOVAhRSByLkCwN|Uh|ryPLh?= MmH6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl{M{myNlkoRjF7MkO5NlI6RC:jPh?=
BA/F3 MmC4R5l1d3SxeHnjbZR6KGG|c3H5 NX2xTGhuS3m2b4TvfIlkcXS7IHHnZYlve3RibX;1d4UhSkFxRkOgZ4VtdHNiZYjwdoV{e2mwZzDFS2ZTKEx6NUjSM3Q4QTCPIH31eIFvfCxiSVO1NEA:KDBwMUig{txONg>? NHiyPHo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUKzPVIzQSd-MUmyN|kzOjl:L3G+
Sf9 NIX0NXRHfW6ldHnvckBie3OjeR?= M4rseFExKG2rboO= NFrzfVRKdmirYnn0bY9vKG:oIHj1cYFvKHerbHSgeJlx\SCHR1\SJIV5eHKnc4Pl[EBqdiCVZkmgZ4VtdHNidYPpcochY2ejbX3hN|JRZS2DVGCgZYZ1\XJiMUCgcYlveyCkeTDzZ4lvfGmubHH0bY9vKGOxdX70bY5oNCCLQ{WwJF0hOC5yMEK1JO69VS5? MoXWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MEC2OFMoRjJ2OUCwOlQ{RC:jPh?=
Sf9 NWT3cZJPTnWwY4Tpc44h[XO|YYm= MmTFNVAhdWmwcx?= NULDcGI4UW6qaXLpeIlwdiCxZjDoeY1idiCHR1\SJHQ4QTCPL1y4OVhTKG23dHHueEBmgHC{ZYPz[YQhcW5iU3[5JINmdGy|IIXzbY5oKFupYX3tZVMzWF1vQWTQJIFnfGW{IEGwJI1qdnNiYomgd4NqdnSrbHzheIlwdiClb4XueIlv\yxiSVO1NEA:KDBwME[2JO69VS5? Mm\JQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MEC2OFMoRjJ2OUCwOlQ{RC:jPh?=
BAF3 NFz1[oVHfW6ldHnvckBie3OjeR?= MXO3NkBpenN? NVPKflBsUW6qaXLpeIlwdiCxZjDU[Ywu\nW|ZXSgTWdHOVJiKIXub45wf25ib4Lp[4lvMSCneIDy[ZN{\WRiaX6gcY92e2ViQlHGN{Bk\WyuczDhd5Nme3OnZDDhd{Boem:5dHigbY5pcWKrdHnvckBi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCjc4PhfUwhT0l3MDC9JFAvOTlizszNMi=> MljJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh{OEKxNlIoRjJ6MkiyNVIzRC:jPh?=
BAF3 MVrGeY5kfGmxbjDhd5NigQ>? NHrrW4U4OiCqcoO= Ml3XTY5pcWKrdHnvckBw\iCWZXyt[pV{\WRiSV7TVkApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCvb4Xz[UBDSUZ|IHPlcIx{KGG|c3Xzd4VlKGG|IHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDd{IHjyd{BjgSCFZXzsWIl1\XJvR3zvJIF{e2G7LDDHTVUxKD1iMD6yPUDPxE1w MmLEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh{OEKxNlIoRjJ6MkiyNVIzRC:jPh?=
BAF3 NXLEVlIxT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= Mn7yO|IhcHK| Mmr3S5Jwf3SqIHnubIljcXSrb36gc4YhdW:3c3WgRmFHOyClZXzsd{Bi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCjc4PhfUwhT0l3MDC9JFEvQSEQvF2u NFH2TpQ9[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

In vivo Formulation Calculator (Clear solution)

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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
NCT04856475 Not yet recruiting Drug: Neratinib Breast Cancer|Brain Metastases Jules Bordet Institute September 1 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|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

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