Home Cytoskeletal Signaling Antineoplastic and Immunosuppressive Antibiotics inhibitor - HSP (HSP90) inhibitor - Autophagy activator - Antiviral inhibitor Geldanamycin (NSC 122750)

Geldanamycin (NSC 122750)

Catalog No.S2713

For research use only.

Geldanamycin (NSC 122750) is a natural existing HSP90 inhibitor with Kd of 1.2 μM, specifically disrupts glucocorticoid receptor (GR)/HSP association. Geldanamycin attenuates virus infection-induced ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) by reducing the host's inflammatory responses.

Geldanamycin (NSC 122750) Chemical Structure

CAS No. 30562-34-6

Selleck's Geldanamycin (NSC 122750) has been cited by 29 publications

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Biological Activity

Description Geldanamycin (NSC 122750) is a natural existing HSP90 inhibitor with Kd of 1.2 μM, specifically disrupts glucocorticoid receptor (GR)/HSP association. Geldanamycin attenuates virus infection-induced ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) by reducing the host's inflammatory responses.
Targets
p185 [4]
(SKBr3 cells)		 HSP90 (N-terminal domain) [1]
(Cell-free assay)		 HSP90 [1]
(Cell-free assay)
70 nM 0.78 μM(Kd) 1.2 μM(Kd)
In vitro

Geldanamycin binds in the ATP-binding site in the N-terminus domain of Hsp90s (residues 1-220). Geldanamycin inhibits the ATPase activity of Hsp90 in a dose-dependent manner. [1] Geldanamycin causes a dose-dependent G2 arrest and reversible inhibiton o f entry into the S phase in A2780 human ovarian cell line. This inhibition is accompanied by p53 increase and finally demonstrated to be p53 dependent. [2] Geldanamycin causes polyubiquitination and proteasomal degradation of the p185 receptor protein-tyrosin kinase and shows a IC50 with 70 nM. [3, 4] Geldanamycin is a typical anti-tumor reagent, shows a mean GI50 with 0.18 μM against the panel of 60 human tumor cell lines. [5]
Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A2780 cells NWXWdI9GWHKxbHnm[ZJifGmxbjDhd5NigQ>? M4\ZUWNwdXCxdX7kJJdieyCndnHseYF1\WRiZn;yJIFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5ib4\hdolidiClYYLjbY5wdWFiY3XscEBtcW6nIFGyO|gxNCCLQ{WwQVMvPCEQvF2= NGDRZWs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zMUWxOFE1PSd-MUG1NVQyPDV:L3G+
SW620 cell NWToe2llT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= M3f0d2lvcGmkaYTvdpkh[2:wY3XueJJifGmxbjDh[4FqdnO2IHj1cYFvKGOxbH;y[YN1[WxiY3HyZ4lvd22jIGPXOlIxKGOnbHygcIlv\XNuIFnDOVA:Pi5{IH7N MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPTZ3OEi3PUc,OTV4NUi4O|k9N2F-
MCF-7 cell Mn3mS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MlS3TY5pcWKrdH;yfUBkd26lZX70doF1cW:wIHHnZYlve3RiaIXtZY4h[nKnYYP0JINidmOncjDNR2YuPyClZXzsJIxqdmW|LDDJR|UxRTZwNTDuUS=> MmPvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTV4NUi4O|koRjF3NkW4PFc6RC:jPh?=
K562 cell MkfZS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MXTJcohq[mm2b4L5JINwdmOnboTyZZRqd25iYXfhbY5{fCCqdX3hckBt\XWtZX3pZUBMPTZ{IHPlcIwhdGmwZYOsJGlEPTB;MkKuNUBvVQ>? MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPTZ3OEi3PUc,OTV4NUi4O|k9N2F-
HT-29 cell NInkRnRIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MnnHTY5pcWKrdH;yfUBkd26lZX70doF1cW:wIHHnZYlve3RiaIXtZY4h[2:ub4LlZ5RidCClYYLjbY5wdWFiSGStNlkh[2WubDDsbY5meyxiSVO1NF0zPC53IH7N MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPTZ3OEi3PUc,OTV4NUi4O|k9N2F-
SK-BR-3 NXyzZXJRTnWwY4Tpc44h[XO|YYm= MnzCOVAhdWdxa3e= NGDmUmhKdmirYnn0bY9vKG:oIH;uZ49o\W6nIIDyc4R2[3RicEG4OUBmemKELUKg[pJwdSCqdX3hckBjemWjc4SgZ4Fv[2W{IHPlcIx{MFONLVLSMVMh[2WubIOpJIF1KDVyIH3nM4toKGSxc3WsJGlEPTB;MD6wO:69VQ>? NU\TdmE{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxN{W2NlkyOSd-N{W2NlkyOTxxYU6=
SK-BR-3 NGLwOG1HfW6ldHnvckBie3OjeR?= NFn4VXZKdiC4aYTyc{BqdmirYnn0bY9vKG:oIICxPFUh\XKkQj2yJI9v[2:ycn;0[YlvKGmwIHj1cYFvKGK{ZXHzeEBk[W6lZYKgV2suSlJvMzDj[YxteyxiSVO1NF0xNjB5zszN MnXZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwPzV4MkmxNkc,PzV4MkmxNlww[T5?
MCF-7 NYXZe5Z1TnWwY4Tpc44h[XO|YYm= MWLJcohq[mm2aX;uJI9nKHO2ZXHkfU1{fGG2ZTDlfJBz\XO|aX;uJI9nKEiHUkKgbY4hVUOILUegZpJm[XO2IHPhcoNmeiClZXzsd{whUUN3ME2wMlA2|ryP MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yODN2ME[wOUc,OTB|NEC2NFU9N2F-
MCF-7 NWe2OYxHTnWwY4Tpc44h[XO|YYm= MWPJcohq[mm2aX;uJI9nKHO2ZXHkfU1{fGG2ZTDlfJBz\XO|aX;uJI9nKEWUIHnuJG1ETi15IHLy[YF{fCClYX7j[ZIh[2WubIOsJGlEPTB;MD6wOu69VQ>? M4\kT|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzFyM{SwOlA2Lz5zMEO0NFYxPTxxYU6=
MCF-7 M1;rTWZ2dmO2aX;uJIF{e2G7 M33qVWlvcGmkaYTpc44hd2Zic4TlZYR6NXO2YYTlJIV5eHKnc4Ppc44hd2ZiUnHmMVEhcW5iTVPGMVch[nKnYYP0JINidmOncjDj[YxteyxiSVO1NF0xNjMQvF2= NGjHdlM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zMEO0NFYxPSd-MUCzOFA3ODV:L3G+
SKBR-3 Mn7NSpVv[3Srb36gZZN{[Xl? MW\F[oZm[3SrdnWgZ49v[2WwdILheIlwdiCob4KgTIVzNTJiZHXndoFl[XSrb36gbY4hW0uEUj2zJINmdGy|LDDDc45k\W62cnH0bY9vRTYQvF2= M{DrXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF3N{GzOFExLz5zNUexN|QyODxxYU6=
HEK293 NITNXllHfW6ldHnvckBie3OjeR?= M1q4TWlvcGmkaYTpc44hd2ZiSGPQPVAh\XiycnXzd4VlKGmwIFjFT|I6OyClZXzsd{Bie3Onc4Pl[EBieyCnZn\lZ5Qhd25iQXv0NVpxOjdiaX70[ZJi[3Srb36gZ49ueGyneHXzJIJ6KEW\RmCgZY5lN2:{IGnGVEBX\W63czDmdoFodWWwdDDiZZNm\CC{ZYDvdpRmeiCpZX7lJIF{e2G7 MofJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTZ4OECxOVkoRjF4NkiwNVU6RC:jPh?=
LS174T NVnIOnZOS3m2b4TvfIlkcXS7IHHzd4F6 NInuOmdEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBNWzF5NGSgZ4VtdHNiYomgUXRUKGG|c3H5MEBKSzVyPUCuOFXPxE1? M4XKWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5MEO0NVM2Lz5zN{CzOFE{PTxxYU6=
rat neuronal cells NGntU|REgXSxdH;4bYNqfHliYYPzZZk> M3jmd|ExKHWP MoWyNlQhcHK| MnjGR5l1d3SxeHnjbZR6KGGpYXnud5QhemG2IH7leZJwdmGuIHPlcIx{KGG2IEGwJJVOKGGodHXyJFI1KGi{cx?= M3WxOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5Mke2Olc6Lz5zN{K3OlY4QTxxYU6=
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MCF7 NIDMZmNIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NWDGdWRFT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hVUOINzDj[YxteyCjZoTldkBl[Xm|IHL5JHNTSiCjc4PhfUwhT0l3ME2zOU43|ryP NUfw[GRlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUe4OlkxQThpPkG3PFY6ODl6PD;hQi=>
HCT116 MUHHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NWrKZ5dOT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hUEOWMUG2JINmdGy|LDDHTVUxRTBwMEKx{txO NVXlXJRHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUiyOFM4ODNpPkG4NlQ{PzB|PD;hQi=>
DLD1 NXzQ[GhiT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NWL4bXZoT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hTEyGMTDj[YxteyxiR1m1NF0xNjB|N988US=> M2LY[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MkSzO|A{Lz5zOEK0N|cxOzxxYU6=
KPL4 NYX5emhlT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NETWNIVIem:5dHigbY5pcWKrdHnvckBw\iCqdX3hckBMWEx2IHPlcIx{NCCJSUWwQVAvODV7zszN MkGxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh{NEO3NFMoRjF6MkSzO|A{RC:jPh?=
A549 MmntS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MV3Hdo94fGhiaX7obYJqfGmxbjDv[kBpfW2jbjDBOVQ6KGOnbHzzMEBIUTVyPUCuNFY1|ryP NEHvSWg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEK0N|cxOyd-MUiyOFM4ODN:L3G+
KPL4 NIiybIhHfW6ldHnvckBie3OjeR?= MkfXOFAhcHK| M4fDXmlvcGmkaYTpc44hd2ZiSIPwPVAhcW5iaIXtZY4hU1CONDDj[YxteyCjc4Pld5Nm\CCjczDk[ZBt\XSrb36gc4YhTXKkQkKgcIV3\WxiYX\0[ZIhPDBiaILzMEBOTUN;MD6xNe69VQ>? MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDJ2M{ewN{c,OTh{NEO3NFM9N2F-
KPL4 NFz2XHBHfW6ldHnvckBie3OjeR?= M{DlfFQxKGi{cx?= NYnpVmFzUW6qaXLpeIlwdiCxZjDId5A6OCCrbjDoeY1idiCNUFy0JINmdGy|IHHzd4V{e2WmIHHzJIRmeGyndHnvckBw\iCUYX[tNUBt\X[nbDDh[pRmeiB2MDDodpMtKE2HQ{2wMlM{|ryP MkjuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh{NEO3NFMoRjF6MkSzO|A{RC:jPh?=
Jurkat M{TH[GZ2dmO2aX;uJIF{e2G7 MmG5NUB2VQ>? MnrMTY5pcWKrdHnvckBw\iC2bzDIV3A6OCCrbjDGRWRFKGSnZnnjbYVvfCCqdX3hckBLfXKtYYSgZ4VtdHNiYYPz[ZN{\WRiYYOgVmlRKHC{b4TlbY4h\GWpcnHkZZRqd25iYYSgNUB2VSCkeTDX[ZN1\XKwIHLsc5Q> NVTvZmVZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi0NFg4OTNpPkG4OFA5PzF|PD;hQi=>
HEK293T MW\GeY5kfGmxbjDhd5NigQ>? MnLRTY5pcWKrdHnvckBw\iCWTl[tZYxxcGFvaX7keYNm\CCQRj3rZZBx[UJiYXP0bZZifGmxbjDlfJBz\XO|ZXSgbY4hUEWNMkmzWEBk\WyuczDifUBtfWOrZnXyZZNmKHKncH;yeIVzKGenbnWgZZN{[Xl? NX\yNmc{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi0NFg4OTNpPkG4OFA5PzF|PD;hQi=>
Jurkat MU\GeY5kfGmxbjDhd5NigQ>? NFvyNnVKdmirYnn0bY9vKG:oIGTOSk1idHCqYT3pcoR2[2WmIF7GMYtieHCjQjDhZ5RqfmG2aX;uJIV5eHKnc4Pl[EBqdiCIQVTEJIRm\mmlaXXueEBpfW2jbjDKeZJs[XRiY3XscJMh[nlibIXjbYZmemG|ZTDy[ZBwenSncjDn[Y5mKGG|c3H5 MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDRyOEexN{c,OTh2MEi3NVM9N2F-
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HuH7 NIG3WllCdnSrdnnyZYwh[XO|YYm= M3KzN|Mh\GG7cx?= NXPJfpV6SW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUGWyYYTpeIl{KENidnnyeZMh\2Wwb4T5dIUhOWJiQ3;uNUBqdm[nY4Tl[EBqdiCqdX3hckBJfUh5IHPlcIx{KGG|c3Xzd4VlKGG|IFfBVGRJKFKQQTDvdkAyQFNicmLORUBt\X[nbDDh[pRmeiB|IHThfZMhe2WuZXP0[YQhf2m2aDC0NEBvVSCKQ2[tO|k3KGGwZDC4NFAhdk1iYn;j[ZBz\X[rcjDifUByWlRvUFPSJIFv[Wy7c3nzMEBGSzVyPUCuNFAyOs7:TR?= MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDl|NkG5NUc,OTh7M{[xPVE9N2F-
SH-SY5Y MnvsUoV2em:ycn;0[YN1cW:wIHHzd4F6 MoHMUoV2em:ycn;0[YN1cW:wIHHnZYlve3RiYnX0ZU1idXmub3nkJJBmeHSrZHWgNU01Oi2rbnT1Z4VlKHSxeHnjbZR6KGmwIHj1cYFvKFOKLWPZOXkh[2WubIOgZZN{\XO|ZXSgZZMhdGGldHH0[UBl\Wi7ZILv[4Vv[XOnIILlcIVie2VuIFXDOVA:OC5yNEK2Pe69VQ>? NF\jOpE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUGzPFg2QSd-MUmxN|g5PTl:L3G+
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Click to View More Cell Line Experimental Data
In vivo Geldanamycin (50 mg//kg) shows 30% inhibition on pl85-associated phosphotyrosine levels in FRE/erbB-2 mice. [6]

Protocol (from reference)

Kinase Assay:

[1]
  • Isothermal Titration Calorimetry (ITC) of Nucelotide Binding:

    The titration experiments are performed using the MSC system. In each experiment, 16 aliquots of 15 μL of geldanamycin (300 μM in 1% DMSO) are injected into 1.3 mL of protein (31 μM in 20 mMTris-HCl, pH 7.5, 1 mMEDTA) at 25 °C, and the resulting data are fit after subtracting the heats of dilution. Heats of dilution are determined in separate experiments from addition of geldanamycin into buffer and buffer into protein. No evidence for binding of DMSO in the nucleotide binding site is observed. Titration data are fit using a nonlinear least-squares curve-fitting algorithm with three floating variables: stoichiometry, binding constant (Kb) 1/Kd), and change of enthalpy of interaction (ΔH°). Dissociation constants estimated for geldanamycin binding to intact yeast Hsp90 is 1.22 μM, and for binding to Hsp90 N-terminal domain is 0.78 μM. No meaningful heat is observed with binding to the C-terminal fragment.
Cell Research:

[2]
  • Cell lines: A2780 human ovarian cell line
  • Concentrations: 0.001-10 μM
  • Incubation Time: 3 hours
  • Method:

    Exponentially growing cells are treated with Geldanamycin and at various times DNA synthesis is assessed by incorporation of bromodeoxyuridine (BrdUrd) and flow cytometric analysis. No marked difference in total cell number is noted during this time course for treated and untreated cultures. BrdUrd (10 μM) is incorporated over a 4-h incubation period at 37 °C and cells are harvested and fixed in 70% ethanol. After denaturation of the DNA with 2 N HC1, cells are incubated with an anti-BrdUrd mouse monoclonal antibody followed by a fluorescein isothiocyanate (FITC)-linked goat anti-mouse IgG. Cells are stained for 30 minutes at room temperature with propidium iodide and analysed by flow cytometry using a Coulter EPICS Profile Analyzer.
Animal Research:

[6]
  • Animal Models: FRE/erbB-2 tumors in nu/nu mice
  • Dosages: 50 mg/kg
  • Administration: Administered via i.p.

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 560.64
Formula

C29H40N2O9
CAS No. 30562-34-6
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)OC)C)OC)OC(=O)N)C)C)O)OC

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
NCT00003969 Completed Drug: tanespimycin Unspecified Adult Solid Tumor Protocol Specific Cancer Research UK|National Cancer Institute (NCI) August 1998 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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