PIM447 (LGH447)

Catalog No.S7985

For research use only.

PIM447 (LGH447) is a novel pan-PIM kinase inhibitor with Ki values of 6 pM, 18 pM, 9 pM for PIM1, PIM2, PIM3 respectively. It also inhibits GSK3β, PKN1, and PKCτ, but at a significantly lower potency with IC50 between 1 and 5 μM (>105-fold differential relative to the Ki on PIMs). PIM447 induces apoptosis.

PIM447 (LGH447) Chemical Structure

CAS No. 1210608-43-7(freebase)

Selleck's PIM447 (LGH447) has been cited by 13 publications

Purity & Quality Control

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Biological Activity

Description PIM447 (LGH447) is a novel pan-PIM kinase inhibitor with Ki values of 6 pM, 18 pM, 9 pM for PIM1, PIM2, PIM3 respectively. It also inhibits GSK3β, PKN1, and PKCτ, but at a significantly lower potency with IC50 between 1 and 5 μM (>105-fold differential relative to the Ki on PIMs). PIM447 induces apoptosis.
Targets
Pim1 [1]
(Cell-free assay)
Pim3 [1]
(Cell-free assay)
Pim2 [1]
(Cell-free assay)
6 pM(Ki) 9 pM(Ki) 18 pM(Ki)
In vitro

The kinase selectivity of PIM447 is first determined in biochemical assays for a panel of 68 diverse protein kinases that included PIM2 as well as 9 lipid kinases. In this panel, only PIM2 is significantly inhibited by PIM447 with an IC50 of <0.003 μM, the lowest sensitivity range for the assay. PIM447 also inhibits GSK3β, PKN1, and PKCτ, but at a significantly lower potency with IC50 between 1 and 5 μM (>105-fold differential relative to the Ki on PIMs). The biochemical IC50 for all other kinases tested in this panel is >9 μM. In follow-up cellular assays of GSK3β inhibition, PIM447 is tested up to 20 μM and is not active[1]. PIM447 is cytotoxic for myeloma cells due to cell-cycle disruption and induction of apoptosis mediated by a decrease in phospho-Bad (Ser112) and c-Myc levels and the inhibition of mTORC1 pathway. PIM447 also inhibits in vitro osteoclast formation and resorption, downregulates key molecules involved in these processes, and partially disrupts the F-actin ring, while increasing osteoblast activity and mineralization[2].

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MOLM16 NWjCUGNGSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NGf1WVU{KGSjeYO= MnHFRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCPT1zNNVYh[2WubIOgZYZ1\XJiMzDkZZl{KGK7IFPlcIxVcXSncj3HcI8h[XO|YYmsJGdKPTB;MD6wNe69VQ>? NYHKcHN[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1NFU5QThpPkK2OVA2QDl6PD;hQi=>
KG1 M{fqb2FvfGmycn;sbYZmemG2aY\lJIF{e2G7 MoO4N{Bl[Xm| NEi1VZpCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFvHNUBk\WyuczDh[pRmeiB|IHThfZMh[nliQ3XscHRqfGW{LVfsc{Bie3OjeTygS2k2OD1yLkCx{txO MlLOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3MEW4PVgoRjJ4NUC1PFk5RC:jPh?=
EOL-1 MUTBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? MVmzJIRigXN? M{S3[GFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iRV;MMVEh[2WubIOgZYZ1\XJiMzDkZZl{KGK7IFPlcIxVcXSncj3HcI8h[XO|YYmsJGdKPTB;MD6wNe69VQ>? NVewPZVuRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1NFU5QThpPkK2OVA2QDl6PD;hQi=>
M07e MnvaRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? M4DWe|Mh\GG7cx?= NVm5ZVdrSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNNFdmKGOnbHzzJIFnfGW{IEOg[IF6eyCkeTDD[YxtXGm2ZYKtS4xwKGG|c3H5MEBIUTVyPUCuNFXPxE1? M1T0T|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NUC1PFk5Lz5{NkWwOVg6QDxxYU6=
UKE1 NX3tbGRDSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= MV:zJIRigXN? NVHuNmJDSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDVT2UyKGOnbHzzJIFnfGW{IEOg[IF6eyCkeTDD[YxtXGm2ZYKtS4xwKGG|c3H5MEBIUTVyPUCuNFnPxE1? NFjnPWQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkWwOVg6QCd-Mk[1NFU5QTh:L3G+
MV411 MkOyRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? MofkN{Bl[Xm| NH;tW2RCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3WOFEyKGOnbHzzJIFnfGW{IEOg[IF6eyCkeTDD[YxtXGm2ZYKtS4xwKGG|c3H5MEBIUTVyPUCuNVPPxE1? MnHPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3MEW4PVgoRjJ4NUC1PFk5RC:jPh?=
KMS11 NFrEUIZCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MW[3NkBpenN? NVK0WGkxSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBtfWOrZnXyZZNmKGW6cILld5NqdmdiaIXtZY4hU02VMUGgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KEOnbHytWIl1\XKJbH:gZZN{[XluIFXDOVA:OC5zN988US=> M4rxZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NUC1PFk5Lz5{NkWwOVg6QDxxYU6=
KMS11 NGXyeo1HfW6ldHnvckBie3OjeR?= MWOxJIhz MkLpTY5pcWKrdHnvckBw\iCSSV2gb4lv[XOnIHnuJIx2[2moZYLhd4Uh\XiycnXzd4lv\yCqdX3hckBMVVNzMTDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKHCqb4PwbI9zgWyjdHnvckBw\iCVNmLQJIFnfGW{IEGgbJIh[nliZXzlZ5Rzd2OqZX3pcJVucW6nc3PlcoNmKGG|c3H5MEBGSzVyPUCuNVjPxE1? MkPyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3MEW4PVgoRjJ4NUC1PFk5RC:jPh?=
CMK NVfEe2VYSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= M3TJb|Mh\GG7cx?= MYfBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEOPSzDj[YxteyCjZoTldkA{KGSjeYOgZpkhS2WubGTpeIVzNUeubzDhd5NigSxiR1m1NF0xNjJ6zszN MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjVyNUi5PEc,OjZ3MEW4PVg9N2F-
KG1 MYHGeY5kfGmxbjDhd5NigQ>? MkjKNVAxKG2pL3vn MnrBNlQhcHK| MoHNWY5jd3WwZDDwcIF{dWFiY3;uZ4VvfHKjdHnvckBqdiCvb4Xz[UB5\W6xZ4Lh[pRm\CC5aYToJIh2dWGwIFvHNUBk\WyuczDheEAyODBibXevb4ctKHCxIHHmeIVzKDJ2IHjyd{BjgSCOQz;NV{9OWyCjbnHsfZNqeyxiQ4Co[kk:OC5|zszN MnjYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3MEW4PVgoRjJ4NUC1PFk5RC:jPh?=
SET2 M{LKdGFvfGmycn;sbYZmemG2aY\lJIF{e2G7 MlrWN{Bl[Xm| NFTaWItCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGPFWFIh[2WubIOgZYZ1\XJiMzDkZZl{KGK7IFPlcIxVcXSncj3HcI8h[XO|YYmsJGdKPTB;MD60PO69VQ>? M{\oNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NUC1PFk5Lz5{NkWwOVg6QDxxYU6=
CMK-11-5 M4rWdWFvfGmycn;sbYZmemG2aY\lJIF{e2G7 NV;JelNiOyCmYYnz Mof6RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCFTVutNVEuPSClZXzsd{Bi\nSncjCzJIRigXNiYomgR4VtdFSrdHXyMWdtdyCjc4PhfUwhT0l3ME2xMlA{|ryP Ml3HQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3MEW4PVgoRjJ4NUC1PFk5RC:jPh?=
MOLM13 MUTBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? NIX6V3I{KGSjeYO= M4r3cWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTV;MUVE{KGOnbHzzJIFnfGW{IEOg[IF6eyCkeTDD[YxtXGm2ZYKtS4xwKGG|c3H5MEBIUTVyPUGuN|nPxE1? NUXVSmhwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1NFU5QThpPkK2OVA2QDl6PD;hQi=>
HEL 92.1.7 NID3dlVCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= M4\GXlMh\GG7cx?= M1T5cWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFXMJFkzNjFwNzDj[YxteyCjZoTldkA{KGSjeYOgZpkhS2WubGTpeIVzNUeubzDhd5NigSxiR1m1NF0yNjZ4zszN M{nxeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NUC1PFk5Lz5{NkWwOVg6QDxxYU6=
TF1 M4ixOGFvfGmycn;sbYZmemG2aY\lJIF{e2G7 M2PaeVMh\GG7cx?= NIPiSWhCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGTGNUBk\WyuczDh[pRmeiB|IHThfZMh[nliQ3XscHRqfGW{LVfsc{Bie3OjeTygS2k2OD1zLkm2{txO NEDFWnc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkWwOVg6QCd-Mk[1NFU5QTh:L3G+
MUTZ8 NVTiR|FjSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NV;xdnJKOyCmYYnz NGPYVnpCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3VWHo5KGOnbHzzJIFnfGW{IEOg[IF6eyCkeTDD[YxtXGm2ZYKtS4xwKGG|c3H5MEBIUTVyPUGuPVnPxE1? M{m4U|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NUC1PFk5Lz5{NkWwOVg6QDxxYU6=
OCI-M1 M1jXbmFvfGmycn;sbYZmemG2aY\lJIF{e2G7 NGKxV3Q{KGSjeYO= MmPPRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCRQ1mtUVEh[2WubIOgZYZ1\XJiMzDkZZl{KGK7IFPlcIxVcXSncj3HcI8h[XO|YYmsJGdKPTB;Mj61O:69VQ>? MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjVyNUi5PEc,OjZ3MEW4PVg9N2F-
SKM1 MkLjRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? M2nRPFMh\GG7cx?= M3\PS2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU1vNNUBk\WyuczDh[pRmeiB|IHThfZMh[nliQ3XscHRqfGW{LVfsc{Bie3OjeTygS2k2OD1{Lk[5{txO M{joNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NUC1PFk5Lz5{NkWwOVg6QDxxYU6=
OCI-AML3 NYr1[HdnSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NHviTHA{KGSjeYO= M{PG[2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iT1PJMWFOVDNiY3XscJMh[W[2ZYKgN{Bl[Xm|IHL5JGNmdGyWaYTldk1IdG9iYYPzZZktKEeLNUC9Nk46Os7:TR?= MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjVyNUi5PEc,OjZ3MEW4PVg9N2F-
P31/FUJ NIXYbZFCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MYqzJIRigXN? MXjBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFB|MT;GWWoh[2WubIOgZYZ1\XJiMzDkZZl{KGK7IFPlcIxVcXSncj3HcI8h[XO|YYmsJGdKPTB;NT6wOu69VQ>? NHrIbWo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkWwOVg6QCd-Mk[1NFU5QTh:L3G+
MONO-MAC-1 M2nRT2FvfGmycn;sbYZmemG2aY\lJIF{e2G7 NGTRe4E{KGSjeYO= Mn3hRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCPT17PMW1CSy1zIHPlcIx{KGGodHXyJFMh\GG7czDifUBE\WyuVHn0[ZIuT2yxIHHzd4F6NCCJSUWwQVUvOToQvF2= MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjVyNUi5PEc,OjZ3MEW4PVg9N2F-
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OCI-AML2 M1TBUGFvfGmycn;sbYZmemG2aY\lJIF{e2G7 NFzxfZU{KGSjeYO= NYPNTnpvSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDPR2kuSU2OMjDj[YxteyCjZoTldkA{KGSjeYOgZpkhS2WubGTpeIVzNUeubzDhd5NigSxiR1m1NF02NjV|zszN MmfKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3MEW4PVgoRjJ4NUC1PFk5RC:jPh?=
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PL21 NY\ZeIJnSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NYf5T|BMOyCmYYnz MoXGRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCSTEKxJINmdGy|IHHmeIVzKDNiZHH5d{BjgSCFZXzsWIl1\XJvR3zvJIF{e2G7LDDHTVUxRThwNUdOwG0> MlnlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3MEW4PVgoRjJ4NUC1PFk5RC:jPh?=
SIG-M5 MknKRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? NWXXSmNTOyCmYYnz M2fZcmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU1nHMW02KGOnbHzzJIFnfGW{IEOg[IF6eyCkeTDD[YxtXGm2ZYKtS4xwKGG|c3H5MEBIUTVyPUiuOlbPxE1? MmK5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3MEW4PVgoRjJ4NUC1PFk5RC:jPh?=
NOMO1 MlTpRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? M{HpSFMh\GG7cx?= MWHBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE6RTV:xJINmdGy|IHHmeIVzKDNiZHH5d{BjgSCFZXzsWIl1\XJvR3zvJIF{e2G7LDDHTVUxRTFyzszN NX7iR3YzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1NFU5QThpPkK2OVA2QDl6PD;hQi=>
F-36P MWjBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? NHjyR2k{KGSjeYO= NH7uVplCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF[tN|ZRKGOnbHzzJIFnfGW{IEOg[IF6eyCkeTDD[YxtXGm2ZYKtS4xwKGG|c3H5MEBIUTVyPUGw{txO MlfpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3MEW4PVgoRjJ4NUC1PFk5RC:jPh?=
OCI-AML5 NIrlfpBCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= Ml\3N{Bl[Xm| MkDYRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCRQ1mtRW1NPSClZXzsd{Bi\nSncjCzJIRigXNiYomgR4VtdFSrdHXyMWdtdyCjc4PhfUwhT0l3ME2xNO69VQ>? M{fWd|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NUC1PFk5Lz5{NkWwOVg6QDxxYU6=
KG1 NXv1U3ZkSW62aYT1cY9zKGG|c3H5 NUL5eJpVOzBibXevb4c> MofLNVEh\GG7cx?= MljlRY51cXS3bX;yJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iS1exJINmdGy|IIjlco9oemGodHXkJIlvKG2xdYPlJIF{e2W|c3XkJIF{KHS3bX;yJJN1[XOrczDheEA{OCCvZz;r[{wheG9icXSgcYVie3W{ZXSgZYZ1\XJiMUGg[IF6eyCyb4P0JJR2dW:{IHntdIxidnSjdHnvci=> NHrhUYg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkWwOVg6QCd-Mk[1NFU5QTh:L3G+
KG1 MoixRY51cXS3bX;yJIF{e2G7 M3zQV|MxKHSxIEGwNEBu\y:tZx?= NV;D[plwOTFiZHH5dy=> MVPBcpRqfHWvb4KgZYN1cX[rdImgZYdicW6|dDDoeY1idiCNR{GgZ4VtdHNieHXuc4dz[W[2ZXSgbY4hdW:3c3WgZZN{\XO|ZXSgZZMhfHWvb4KgdoVoemW|c3nvckBifCB|MDD0c{AyODBibXevb4ctKHCxIIHkJI1m[XO3cnXkJIFnfGW{IEGxJIRigXNicH;zeEB1fW2xcjDpcZBt[W62YYTpc44hcW5icILld4Vv[2Vib3[gNVAxKG2pL3vnJGFz[S2F NYHkbWpwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1NFU5QThpPkK2OVA2QDl6PD;hQi=>
In vivo Low to moderate in vivo CL is observed for PIM447 across species, as CL values of 20, 28, and 8 mL/min/kg are observed in mouse, rat, and dog, respectively. The volume of distribution is consistently large across species, with Vss of 5.3, 6.4, and 3.6 L/kg observed in mouse, rat, and dog, respectively. Additionally, PIM447 exhibits high oral bioavailability across species, as 84%, 70%, and 71% is observed in mouse, rat, and dog, respectively. The stability of PIM447 in human plasma is high, >90% after a 3 h incubation, and the human plasma protein binding of PIM447 is 95%. With the combination of potent in vitro activity and low to moderate CL, PIM447 demonstrates in vivo target modulation (pS6RP), single agent antitumor activity in a KG-1 AML mouse xenograft model, and druglike properties suitable for development[1]. PIM447 significantly reduces the tumor burden and prevents tumor-associated bone loss in a disseminated murine model of human myeloma[2].

Protocol (from reference)

Cell Research:

[1]

  • Cell lines: KG-1 cells
  • Concentrations: 0.05, 0.5, and 5 μM
  • Incubation Time: 2 h
  • Method:

    Following treatment of KG-1 cells with PIM447 for 2 h at the indicated concentrations, cells are lysed in RIPA buffer. Protein concentration is determined using a BCA assay, and 50 μg of lysate is separated by SDS-PAGE using 10% bis-Tris gels. Proteins are transferred onto 0.2 μm nitrocellulose membrane, and pS6RP/total S6RP are detected. Following incubation with secondary antibodies, antibody binding is detected using ECL Advance.

Animal Research:

[1]

  • Animal Models: KG-1 AML xenograft mouse model 
  • Dosages: 30 or 100 mg/kg
  • Administration: oral administration

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 476.92
Formula

C24H23F3N4O.HCl

CAS No. 1210608-43-7(freebase)
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1CC(CC(C1)N)C2=C(C=NC=C2)NC(=O)C3=NC(=C(C=C3)F)C4=C(C=CC=C4F)F

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
NCT02160951 Completed Drug: LGH447 Multiple Myeloma Novartis Pharmaceuticals|Novartis September 2014 Phase 1
NCT02078609 Completed Drug: LGH447|Drug: LGH447 + midostaurin AML and High Risk MDS Novartis Pharmaceuticals|Novartis March 20 2014 Phase 1
NCT01456689 Completed Drug: LGH447|Drug: midazolam Multiple Myeloma Novartis Pharmaceuticals|Novartis April 25 2012 Phase 1

(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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