Alvespimycin (17-DMAG) HCl

Catalog No.S1142 Synonyms: NSC 707545,BMS 826476 HCl,KOS 1022

For research use only.

Alvespimycin (17-DMAG, NSC 707545, BMS 826476, KOS 1022) HCl is a potent HSP90 inhibitor with IC50 of 62 nM in a cell-free assay. Phase 2.

Alvespimycin (17-DMAG) HCl Chemical Structure

CAS No. 467214-21-7

Selleck's Alvespimycin (17-DMAG) HCl has been cited by 54 publications

Purity & Quality Control

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Biological Activity

Description Alvespimycin (17-DMAG, NSC 707545, BMS 826476, KOS 1022) HCl is a potent HSP90 inhibitor with IC50 of 62 nM in a cell-free assay. Phase 2.
Features A synthetic derivative Geldanamycin, with lower hepatotoxicity than parent antibiotic & higher potency and bioavailability than the similar derivative 17-AAG.
Targets
HSP90 [1]
(Cell-free assay)
62 nM
In vitro

17-DMAG displays ~2 times potency against human Hsp90 than 17-AAG, with IC50 of 62 nM versus 119 nM. In SKBR3 and SKOV3 cells which over-express Hsp90 client protein Her2, 17-DMAG causes down-regulation of Her2 with EC50 of 8 nM and 46 nM, respectively, as well as induction of Hsp70 with EC50 of 4 nM and 14 nM, respectively, leading to significant cytotoxicity with GI50 of 29 nM and 32 nM, respectively, consistent with Hsp90 inhibition. [1] 17-DMAG in combination with vorinostat synergistically induces apoptosis of the cultured MCL cells as well as primary MCL cells, more potently than either agent alone, by markedly attenuating the levels of cyclin D1 and CDK4, as well as of c-Myc, c-RAF and Akt. [3] In contrast to 17-AAG which is only active for IKKβ in chronic lymphocytic leukemia (CLL) cells, 17-DMAG treatment effectively leads to depletion of the Hsp90 client protein, resulting in diminished NF-κB p50/p65 DNA binding, decreased NF-κB target gene transcription, and caspase-dependent apoptosis. By targeting the NF-κB family, 17-DMAG selectively mediates dose- and time-dependent cytotoxicity against CLL cells, but not normal T cells or NK cells important for immune surveillance. [5]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
SKBr3 M2r0S2N6fG:2b4jpZ4l1gSCjc4PhfS=> NETlUnJEgXSxdH;4bYNqfHliYXfhbY5{fCCVS1LyN{Bk\WyuczygTWM2OD1yLkCyOO69VS5? NFm0OZk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNkG2OVM2PCd-MU[xOlU{PTR:L3G+
SKBR3 MnHpSpVv[3Srb36gZZN{[Xl? NGfmXGpWeHKnZ4XsZZRqd25ib3[gTJNxPzBiaX6gV2tDWjNiY3XscJMtKEWFNUC9NE4xODUQvF2u MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPjh3NEC2Okc,OTZ6NUSwOlY9N2F-
SKBR3 MWHGeY5kfGmxbjDhd5NigQ>? M3jHWmRm\3KjZHH0bY9vKG:oIFjldlIhcW5iU1vCVlMh[2WubIOsJGVEPTB;MD6wNFjPxE1w MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPjh3NEC2Okc,OTZ6NUSwOlY9N2F-
SKOV3 M1[xbmZ2dmO2aX;uJIF{e2G7 NVPpOoFQXXC{ZXf1cIF1cW:wIH;mJGh{eDdyIHnuJHNMV1Z|IHPlcIx{NCCHQ{WwQVAvODF2zszNMi=> MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPjh3NEC2Okc,OTZ6NUSwOlY9N2F-
SKOV3 MWDGeY5kfGmxbjDhd5NigQ>? NFnKc25F\We{YXTheIlwdiCxZjDI[ZIzKGmwIGPLU3Y{KGOnbHzzMEBGSzVyPUCuNFQ3|ryPLh?= MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPjh3NEC2Okc,OTZ6NUSwOlY9N2F-
AGS M2P1VmZ2dmO2aX;uJIF{e2G7 Ml;VNVYhcHK| NIfjUYlKdmirYnn0bY9vKG:oIFjJSlEh[WO2aY\heIlwdiCrbjDoeY1idiCDR2OgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iCqeYDvfIliNWmwZIXj[YQhdHWlaX\ldoF{\SCneIDy[ZN{cW:wIHHmeIVzKDF4IHjyd{BjgSC{ZYDvdpRmeiCjc4PhfUwhUUN3ME2wMlA{Ps7:TT6= MlvJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTd3OEO5OVAoRjF5NUizPVUxRC:jPh?=
Hep3B M135[mZ2dmO2aX;uJIF{e2G7 NV;sV|RmOTZiaILz Moj3TY5pcWKrdHnvckBw\iCKSV[xJIFkfGm4YYTpc44hcW5iaIXtZY4hUGWyM1KgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iCqeYDvfIliNWmwZIXj[YQhdHWlaX\ldoF{\SCneIDy[ZN{cW:wIHHmeIVzKDF4IHjyd{BjgSC{ZYDvdpRmeiCjc4PhfUwhUUN3ME2wMlA3Oc7:TT6= NELUOXc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{W4N|k2OCd-MUe1PFM6PTB:L3G+
AGS MVTGeY5kfGmxbjDhd5NigQ>? M1LEeFI1KGi{cx?= Mn:xWoli[mmuaYT5JI9nKGi3bXHuJGFIWyClZXzsd{B2dmSncjDuc5Jud3irYzDjc45lcXSrb37zJIFnfGW{IEK0JIhzeyCkeTDNWHQh[XO|YYmsJGlEPTB;MUdOwG0v MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPzV6M{m1NEc,OTd3OEO5OVA9N2F-
NCI-H526 NIG0e29HfW6ldHnvckBie3OjeR?= NHS0VZMyKHWP NIe1RZIzPCCqcoO= NH\sNFFDcW6maX7nJIFn\mmwaYT5JJRwKEiVUEmwJIlvKGi3bXHuJG5EUS2KNUK2JINmdGy|IHH0JFEhfU1iYX\0[ZIhOjRiaILzJIJ6KG[udX;y[ZNk\W6lZTDwc4xiemm8YYTpc44h[XO|YYm= NHnYZ|c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{[wN|U1OCd-MUe2NFM2PDB:L3G+
NCI-H526 MXTGeY5kfGmxbjDhd5NigQ>? MlH2NUB2VQ>? NXPLbHRIQTZiaILz Mke0TY5pcWKrdHnvckBw\iCKU2C5NE1u\WSrYYTl[EBxem:uaX\ldoF1cW:wIH;mJIh2dWGwIF7DTU1JPTJ4IHPlcIx{KGG2IEGgeW0h[W[2ZYKgPVYhcHK|IHL5JJN2dG[xcnjv[IFucW6nIFKgZZN{[Xl? NH;leIw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{[wN|U1OCd-MUe2NFM2PDB:L3G+
AGS NHnkPGNHfW6ldHnvckBie3OjeR?= NHT4bVBKdmirYnn0bY9vKG:oIHj5dI95cWFvaX7keYNm\CCKSV[xJIFkfGm4YYTpc44hcW5iaIXtZY4hSUeVIHPlcIx{KGK7IILldI9zfGW{IHflcoUh[XO|YYmsJGlEPTB;MD6wNFM3|ryPLh?= M3;lXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6M{W5OlMyLz5zOEO1PVY{OTxxYU6=
HeLa MYDGeY5kfGmxbjDhd5NigQ>? MY\Jcohq[mm2aX;uJI9nKFSQRj3hcJBp[S2rbnT1Z4VlKE6ILXvhdJBiSiCjY4TpeoF1cW:wIHnuJIh2dWGwIFjlUIEh[2WubIOsJGlEPTB;MD6xOe69VS5? NYqwXJZJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUizOVk3OzFpPkG4N|U6PjNzPD;hQi=>
HeLa M3TET2N6fG:2b4jpZ4l1gSCjc4PhfS=> NYrK[2xbS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hUGWOYTDj[YxteyCkeTDNWHQh[XO|YYmsJGlEPTB;Mj6wOu69VS5? NEDsUoE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEO1PVY{OSd-MUizOVk3OzF:L3G+
AGS NWTL[XVpS3m2b4TvfIlkcXS7IHHzd4F6 NIPU[Y5EgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBCT1NiY3XscJMh[nliTWTUJIF{e2G7LDDJR|UxRTF4zszNMi=> NFjIS|U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEO1PVY{OSd-MUizOVk3OzF:L3G+
A2058 M1\UcGN6fG:2b4jpZ4l1gSCjc4PhfS=> NYK4ZndDS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSTJyNUigZ4VtdHNiYomgUXRVKGG|c3H5MEBKSzVyPUCuNFAzOc7:TT6= MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDl{OUS4Okc,OTh7Mkm0PFY9N2F-
MDA-MB-231 NVqy[XJiTnWwY4Tpc44h[XO|YYm= MYLJcohq[mm2aX;uJI9nKEi|cEmwJIlvKGi3bXHuJG1FSS2PQj2yN|Eh[2WubIOgZZN{\XO|ZXSgZZMhcGW{MjDk[Ydz[WSjdHnvckwhUUN3ME2wMlAxPDYQvF2u M3yyN|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6OUK5OFg3Lz5zOEmyPVQ5PjxxYU6=
MDA-MB-231 NUTRV2t5S3m2b4TvfIlkcXS7IHHzd4F6 MX\DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNSGEuVUJvMkOxJINmdGy|IHL5JG1VXCCjc4PhfUwhUUN3ME2wMlAxPTkQvF2u MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDl{OUS4Okc,OTh7Mkm0PFY9N2F-
A2058 NEe3V3NHfW6ldHnvckBie3OjeR?= Mn\XTY5pcWKrdHnvckBw\iCKc4C5NEBqdiCqdX3hckBCOjB3ODDj[YxteyxiRVO1NF0xNjByN{pOwG0v Mn3xQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh7Mkm0PFYoRjF6OUK5OFg3RC:jPh?=
MDA-MB-231 NEDtcnFHfW6ldHnvckBie3OjeR?= MkTDTY5pcWKrdHnvckBw\iCKc4C5NEBqdiCqdX3hckBOTEFvTVKtNlMyKGOnbHzzJIF{e2W|c3XkJIF{KEGtdDDk[Ydz[WSjdHnvckwhUUN3ME2wMlAyPzcQvF2u M3rPOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6OUK5OFg3Lz5zOEmyPVQ5PjxxYU6=
A2058 NX3oVZhuTnWwY4Tpc44h[XO|YYm= NG\PVmpKdmirYnn0bY9vKG:oIFjzdFkxKGmwIHj1cYFvKEF{MEW4JINmdGy|IHHzd4V{e2WmIHHzJGFsfCCmZXfyZYRifGmxbjygTWM2OD1yLkCyOFPPxE1w MlHaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh7Mkm0PFYoRjF6OUK5OFg3RC:jPh?=
HuH7 MnHQRY51cX[rcnHsJIF{e2G7 NGLWWGE{KGSjeYO= MULBcpRqfmm{YXygZYN1cX[rdImgZYdicW6|dDDI[ZBifGm2aYOgR{B3cXK3czDn[Y5wfHmyZTCxZkBEd25zIHnu[oVkfGWmIHnuJIh2dWGwIFj1TFch[2WubIOgZZN{\XO|ZXSgZZMhT0GSRFigVm5CKG:{IEG4V{BzWk6DIHzleoVtKGGodHXyJFMh\GG7czDifUByWlRvUFPSJIFv[Wy7c3nzMEBGSzVyPUCuNFAyOs7:TT6= MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDl|NkG5NUc,OTh7M{[xPVE9N2F-
HuH7 NYLNNmNbSW62aY\pdoFtKGG|c3H5 MoHUN{Bl[Xm| Mn\kRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTIVx[XSrdHnzJGMhfmm{dYOg[4Vvd3S7cHWgNYIhS2:wMTDpcoZm[3SnZDDpckBpfW2jbjDIeWg4KGOnbHzzJIF{e2W|c3XkJIF{KEeDUFTIJHJPSSCxcjCxPHMhelKQQTDs[ZZmdCCjZoTldkA{KGSjeYOgd4Vt\WO2ZXSge4l1cCB2MDDuUUBJS1ZvN{m2JIFv\CB6MECgcm0h[m:lZYDy[ZZqeiCkeTDxVnQuWEOUIHHuZYx6e2m|LDDFR|UxRTBwMECzNe69VS5? NYS4PZEyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi5N|YyQTFpPkG4PVM3OTlzPD;hQi=>
SKBR3 Mk[2SpVv[3Srb36gZZN{[Xl? MVrCbY5lcW6pIHHm[olvcXS7IITvJGh{eDlyIHnuJIh2dWGwIGPLRnI{KGOnbHzzMEBKSzVyPUCuNFI1|ryPLh?= NYPlTpAzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUmwNVc2PjJpPkG5NFE4PTZ{PD;hQi=>
Hep3B MWrGeY5kfGmxbjDhd5NigQ>? M1jHT|MxKG2rboO= MYPJcohq[mm2aX;uJI9nKGi7cH;4bYEucW6mdXPl[EBJUUZzYXzwbIEheHKxdHXpckBi[2O3bYXsZZRqd25iaX6gbJVu[W5iSHXwN2Ih[2WubIOgeJJm[XSnZDDmc5IhOzBibXnud{Bu\WG|dYLl[EBi\nSncjCxNkBpenNiYomgW4V{fGW{bjDicI91KGGwYXz5d4l{NCCLQ{WwQVAvODV5Mt88UU4> M{fzNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7MEeyNlE1Lz5zOUC3NlIyPDxxYU6=
Hep3B NVH3WXE3TnWwY4Tpc44h[XO|YYm= MoLzNVYhcHK| NVi4dWVlUW6qaXLpeIlwdiCxZjDofZBwgGmjLXnu[JVk\WRiVlXHSkBxem:2ZXnuJJNm[3KndHnvckBqdiCqdX3hckBJ\XB|QjDj[YxteyCjZoTldkAyPiCqcoOgZpkhTUyLU1GsJGlEPTB;MD6wO|k2|ryPLh?= NGjoOGY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUC3NlIyPCd-MUmwO|IzOTR:L3G+
HCT116 NXXldm9wS3m2b4TvfIlkcXS7IHHzd4F6 MmHWO|IhcHK| Mln0R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gTGNVOTF4IHPlcIx{KGGodHXyJFczKGi{czygTWM2OD1yLkC1O:69VS5? MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTJ|MUi2OEc,OTl{M{G4OlQ9N2F-
SKBR3 M1;qdWN6fG:2b4jpZ4l1gSCjc4PhfS=> MmTnO|IhcHK| MXHDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDTT2JTOyClZXzsd{Bi\nSncjC3NkBpenNuIFnDOVA:OC5yNUlOwG0v NXj3[mQ4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUmyN|E5PjRpPkG5NlMyQDZ2PD;hQi=>
MCF7 NGr3dWFEgXSxdH;4bYNqfHliYYPzZZk> MXm3NkBpenN? MlnLR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUWNHPyClZXzsd{Bi\nSncjC3NkBpenNuIFnDOVA:OC5yN{JOwG0v Ml7HQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl{M{G4OlQoRjF7MkOxPFY1RC:jPh?=
SKOV3 M1\BUGN6fG:2b4jpZ4l1gSCjc4PhfS=> MUO3NkBpenN? NEPVZY5EgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUU0:YMzDj[YxteyCjZoTldkA4OiCqcoOsJGlEPTB;MD6xNlLPxE1w NIXqWmo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUKzNVg3PCd-MUmyN|E5PjR:L3G+
SKBR3 NIGyWGpEgXSxdH;4bYNqfHliYYPzZZk> NH31WWY4OiCqcoO= Mlj3R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV2tDWjNiY3XscJMh[W[2ZYKgO|IhcHK|IHnuJJBz\XOnbnPlJI9nKE6TT{GgbY5pcWKrdH;yJIRq[2:3bXHyc4wtKEmFNUC9NE4zO87:TT6= MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTJ|MUi2OEc,OTl{M{G4OlQ9N2F-
MCF7 M2rVfWN6fG:2b4jpZ4l1gSCjc4PhfS=> MVO3NkBpenN? NIPQU5FEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBOS0Z5IHPlcIx{KGGodHXyJFczKGi{czDpckBxemW|ZX7j[UBw\iCQUV:xJIlvcGmkaYTvdkBlcWOxdX3hdo9tNCCLQ{WwQVAvQDZ{zszNMi=> MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTJ|MUi2OEc,OTl{M{G4OlQ9N2F-
NCI-H596 MkLKR5l1d3SxeHnjbZR6KGG|c3H5 MnHaO|IhcHK| MWnDfZRwfG:6aXPpeJkh[WejaX7zeEBPWTBzLXTl[olkcWWwdDDoeY1idiCQQ1mtTFU6PiClZXzsd{Bi\nSncjC3NkBpenNuIFnDOVA:OS5zzszNMi=> M1Tv[|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7MkOxPFY1Lz5zOUKzNVg3PDxxYU6=
MDA468 M1LoemN6fG:2b4jpZ4l1gSCjc4PhfS=> Mn:1O|IhcHK| M1:0[GN6fG:2b4jpZ4l1gSCjZ3HpcpN1KE6TMEGt[IVncWOrZX70JIh2dWGwIF3ERVQ3QCClZXzsd{Bi\nSncjC3NkBpenNuIFnDOVA:OS54zszNMi=> M{W0N|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7MkOxPFY1Lz5zOUKzNVg3PDxxYU6=
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Assay
Methods Test Index PMID
Western blot HSP90 / HSP70 ; p-Akt / Survivin / MMP2 ; PARP / Cleaved caspase-3 / Cleaved caspase-8 / Cleaved caspase-9 / PUMA ; p-ALK / ALK / p-Akt / Akt / p-ERK / ERK ; α-Tax / α-IKKα / α-IKKβ/ α-NEMO / α-TBK1 / α-p65 / α-p50 28915605 26219569 24109220
Growth inhibition assay Cell proliferation 28915605
In vivo 17-DMAG treatment at 5 mg/kg or 25 mg/kg thrice per week significantly reduces tumor growth of TMK-1 xenografts, by significantly reducing vessel area and numbers of proliferating tumor cells in sections. [2] Consistent the inhibition of FAK signaling in vivo, 17-DMAG treatment at 25 mg/kg three times a week significantly suppresses tumor growth, and metastasis of ME180 and SiHa xenografts in mice. [4] Administration of 17-DMAG at 10 mg/kg for 16 days significantly decreases the white blood cell count and prolongs the survival in a TCL1-SCID transplant mouse model. [5]

Protocol (from reference)

Kinase Assay:[1]
  • Fluorescence polarization (FP)-based competition binding assay:

    This assay utilizes a boron difluoride dipyrromethene (BODIPY) labeled geldanamycin analogue (BODIPY-AG) as a probe and measured fluorescence polarization upon binding of the probe to a protein. Native human Hsp90 protein (α + β isoforms) is isolated from HeLa cells. BODIPY-AG solution is freshly prepared in FP assay buffer (20 mM HEPES-KOH, pH 7.3, 1.0 mM EDTA, 100 mM KCl, 5.0 mM MgCl2, 0.01% NP-40, 0.1 mg/mL fresh bovine γ-globulin (BGG), 1.0 mM fresh DTT, and protease inhibitor from stock solution in DMSO. Competition curves are obtained by mixing 10 μL each of a solution containing BODIPY-AG and Hsp90, and a serial dilution of 17-DMAG freshly prepared in FP assay buffer from stock solution in DMSO. Final concentrations are 10 nM BODIPY-AG, 40 or 60 nM Hsp90, varying concentration of 17-DMAG (0.10 nM-10 μM), and ≤0.25% DMSO in a 384-well microplate. After 3 hours incubation at 30 °C, fluorescence anisotropy (γEx = 485 nm, γEm = 535 nm) is measured on an EnVision 2100 multilabel plate reader. IC50 value of 17-DMAG is obtained from the competition curves.

Cell Research:[5]
  • Cell lines: Chronic lymphocytic leukemia (CLL)
  • Concentrations: Dissolved in DMSO, final concentrations ~1 μM
  • Incubation Time: 24, or 48 hours
  • Method: Cells are exposed to various concentrations of 17-DMAG for 24, or 48 hours. For the assessment of cytotoxicity, MTT reagent is then added, and plates are incubated for an additional 24 hours before spectrophotometric measurement. Apoptosis is determined by staining with annexin V-fluorescein isothiocyanate and propidium iodide (PI).
  • (Only for Reference)
Animal Research:[5]
  • Animal Models: SCID mice engrafted with TCL1 leukemia cells
  • Dosages: 10 mg/kg
  • Administration: Intraperitoneal injection 5 times per week
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 131 mg/mL
(200.54 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
1% DMSO+30% polyethylene glycol+1% Tween 80
For best results, use promptly after mixing.

30 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 653.21
Formula

C32H48N4O8•HCl

CAS No. 467214-21-7
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1CC(C(C(C=C(C(C(C=CC=C(C(=O)NC2=CC(=O)C(=C(C1)C2=O)NCCN(C)C)C)OC)OC(=O)N)C)C)O)OC.Cl

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
NCT00780000 Terminated Drug: Alvespimycin Breast Cancer Bristol-Myers Squibb April 2008 Phase 2
NCT00248521 Unknown status Drug: alvespimycin hydrochloride Unspecified Adult Solid Tumor Protocol Specific Institute of Cancer Research United Kingdom|National Cancer Institute (NCI) October 2005 Phase 1

(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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