Home Cytoskeletal Signaling Antineoplastic and Immunosuppressive Antibiotics Inhibitor Geldanamycin (NSC 122750)

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Geldanamycin (NSC 122750) HSP90 Inhibitor

Kat.nr.: S2713

Geldanamycin är en naturligt förekommande HSP90-hämmare med Kd på 1,2 μM, som specifikt stör glukokortikoidreceptorns (GR)/HSP-association. Geldanamycin dämpar virusinfektionsinducerad ALI (akut lungskada)/ARDS (akut respiratorisk distress syndrom) genom att minska värdens inflammatoriska respons.
Geldanamycin (NSC 122750) Antineoplastic and Immunosuppressive Antibiotics Inhibitor Chemical Structure

Kemisk struktur

Molekylvikt: 560.64

Hoppa till

Kvalitetskontroll (Quality Control)

Batch: Renhet: 99.96%
99.96

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)

Cellinjer Analystyp Koncentration Inkubationstid Formulering Aktivitetsbeskrivning PMID
A2780 cells Proliferation assay Compound was evaluated for antiproliferative activity against human ovarian carcinoma cell line A2780, IC50=3.4 μM 11514145
SW620 cell Growth inhibition assay Inhibitory concentration against human colorectal carcinoma SW620 cell lines, IC50=6.2 nM 15658879
MCF-7 cell Growth inhibition assay Inhibitory concentration against human breast cancer MCF-7 cell lines, IC50=6.5 nM 15658879
K562 cell Growth inhibition assay Inhibitory concentration against human leukemia K562 cell lines, IC50=22.1 nM 15658879
HT-29 cell Growth inhibition assay Inhibitory concentration against human colorectal carcinoma HT-29 cell lines, IC50=24.5 nM 15658879
SK-BR-3 Function assay 50 mg/kg Inhibition of oncogene product p185 erbB-2 from human breast cancer cells(SK-BR-3 cells) at 50 mg/kg dose, IC50=0.07μM 7562911
SK-BR-3 Function assay In vitro inhibition of p185 erbB-2 oncoprotein in human breast cancer SK-BR-3 cells, IC50=0.07μM 7562912
MCF-7 Function assay Inhibition of steady-state expression of HER2 in MCF-7 breast cancer cells, IC50=0.05μM 10340605
MCF-7 Function assay Inhibition of steady-state expression of ER in MCF-7 breast cancer cells, IC50=0.06μM 10340605
MCF-7 Function assay Inhibition of steady-state expression of Raf-1 in MCF-7 breast cancer cells, IC50=0.2μM 10340605
SKBR-3 Function assay Effective concentration for Her-2 degradation in SKBR-3 cells, Concentration=5μM 15713410
HEK293 Function assay Inhibition of HSP90 expressed in HEK293 cells assessed as effect on Akt1:p27 interaction complexes by EYFP and/or YFP Venus fragment based reporter gene assay 16680159
LS174T Cytotoxicity assay Cytotoxicity against human LS174T cells by MTS assay, IC50=0.45μM 17034135
rat neuronal cells Cytotoxicity assay 10 uM 24 hrs Cytotoxicity against rat neuronal cells at 10 uM after 24 hrs 17276679
P19 Cytotoxicity assay 18 hrs Cytotoxicity against mouse P19 cells after 18 hrs, IC50=0.1μM 17442565
MCF7 Growth inhibition assay Growth inhibition of human MCF7 cells after days by SRB assay, GI50=35.6μM 17869098
HCT116 Growth inhibition assay Growth inhibition of human HCT116 cells, GI50=0.021μM 18243703
DLD1 Growth inhibition assay Growth inhibition of human DLD1 cells, GI50=0.037μM 18243703
KPL4 Growth inhibition assay Growth inhibition of human KPL4 cells, GI50=0.059μM 18243703
A549 Growth inhibition assay Growth inhibition of human A549 cells, GI50=0.064μM 18243703
KPL4 Function assay 40 hrs Inhibition of Hsp90 in human KPL4 cells assessed as depletion of ErbB2 level after 40 hrs, MEC=0.11μM 18243703
KPL4 Function assay 40 hrs Inhibition of Hsp90 in human KPL4 cells assessed as depletion of Raf-1 level after 40 hrs, MEC=0.33μM 18243703
Jurkat Function assay 1 uM Inhibition of to HSP90 in FADD deficient human Jurkat cells assessed as RIP protein degradation at 1 uM by Western blot 18408713
HEK293T Function assay Inhibition of TNF-alpha-induced NF-kappaB activation expressed in HEK293T cells by luciferase reporter gene assay 18408713
Jurkat Function assay Inhibition of TNF-alpha-induced NF-kappaB activation expressed in FADD deficient human Jurkat cells by luciferase reporter gene assay 18408713
SKBR3 Function assay 24 hrs Inhibition of Hsp90-mediated HER2 degradation in human SKBR3 cells after 24 hrs by Western blot 18816111
SKBR3 Function assay 24 hrs Inhibition of Hsp90-mediated Raf degradation in human SKBR3 cells after 24 hrs by Western blot 18816111
HuH7 Antiviral assay 3 days Antiviral activity against Hepatitis C virus genotype 1b Con1 infected in human HuH7 cells assessed as GAPDH RNA or 18S rRNA level after 3 days by qRT-PCR analysis, EC50=0.00025μM 18936191
HuH7 Antiviral assay 3 days Antiviral activity against Hepatitis C virus genotype 1b Con1 infected in human HuH7 cells assessed as GAPDH RNA or 18S rRNA level after 3 days selected with 40 nM HCV-796 and 800 nM boceprevir by qRT-PCR analysis, EC50=0.0012μM 18936191
SH-SY5Y Neuroprotection assay Neuroprotection against beta-amyloid peptide 1-42-induced toxicity in human SH-SY5Y cells assessed as lactate dehydrogenase release, EC50=0.04269μM 19138859
SH-SY5Y Neuroprotection assay 10 nM Neuroprotection against beta-amyloid peptide 1-42-induced toxicity in retinoic acid-differentiated human SH-SY5Y cells assessed as lactate dehydrogenase release at 10 nM 19138859
SKBR3 Cytotoxicity assay 72 hrs Cytotoxicity against human SKBR3 cells after 72 hrs by celltiter-glo assay, IC50=0.041μM 19405528
MCF7 Cytotoxicity assay Cytotoxicity against human MCF7 cells by SRB assay, IC50=9.6μM 19560353
SK-BR-3 Antiproliferative assay Antiproliferative activity against human SK-BR-3 cells, IC50=0.0158μM 19896848
MCF7 Antiproliferative assay Antiproliferative activity against human MCF7 cells, IC50=0.0161μM 19896848
A431 Antiproliferative assay 72 hrs Antiproliferative activity against human A431 cells after 72 hrs, IC50=0.2μM 20655237
PP30 Function assay 100 uM 3 hrs Inhibition of human HSP90alpha expressed in yeast PP30 cells co-expressing HSF-lacZ reporter assessed as induction of heat shock response at 100 uM after 3 hrs 21129982
MCF7 Function assay 0.5 uM Inhibition of Hsp90 in human MCF7 cells assessed as Akt degradation at 0.5 uM by Western blot analysis 21273068
MCF7 Function assay 0.5 uM Inhibition of Hsp90 in human MCF7 cells assessed as Raf degradation at 0.5 uM by Western blot analysis 21273068
MCF7 Function assay 0.5 uM Inhibition of Hsp90 in human MCF7 cells assessed as Hsp90 degradation at 0.5 uM by Western blot analysis 21273068
MCF7 Function assay 0.5 uM Inhibition of Hsp90 in human MCF7 cells assessed as Her2 degradation at 0.5 uM by Western blot analysis 21273068
HCT116 Antiproliferative assay 4 days Antiproliferative activity against human HCT116 cells measured on day 4 by Cell titer-glo assay, EC50=0.03μM 21420297
HCT116 Antiproliferative assay Antiproliferative activity against human HCT116 cells by luminescence assay, EC50=0.03μM 21605975
U87 Antiproliferative assay Antiproliferative activity against human U87 cells by luminescence assay, EC50=0.089μM 21605975
HCT116 Antiproliferative assay Antiproliferative activity against human HCT116 cells, IC50=0.03μM 21715165
NCI-H1975 Antiproliferative assay Antiproliferative activity against human NCI-H1975 cells, IC50=0.036μM 21715165
U87MG Antiproliferative assay Antiproliferative activity against human U87MG cells, IC50=0.089μM 21715165
MCF7 Function assay 500 nM 24 hrs Inhibition of Hsp90 in human MCF7 cells assessed as induction of Her2 degradation at 500 nM after 24 hrs by Western blot method 21861487
MCF7 Function assay 500 nM 24 hrs Inhibition of Hsp90 in human MCF7 cells assessed as induction of Raf degradation at 500 nM after 24 hrs by Western blot method 21861487
MCF7 Function assay 500 nM 24 hrs Inhibition of Hsp90 in human MCF7 cells assessed as induction of Akt degradation at 500 nM after 24 hrs by Western blot method 21861487
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells at 72 hrs by MTS assay, IC50=0.053μM 22162786
HepG2 Cytotoxicity assay Cytotoxicity against human HepG2 cells, IC50=0.37μM 22849774
SKBR3 Antiproliferative assay 72 hrs Antiproliferative activity against estrogen receptor deficient human SKBR3 cells after 72 hrs, IC50=0.0085μM 23648180
MCF7 Antiproliferative assay 72 hrs Antiproliferative activity against human MCF7 cells expressing estrogen receptor after 72 hrs, IC50=0.0098μM 23648180
HepG2 Cytotoxicity assay Cytotoxicity against human HepG2 cells by MTT assay, IC50=0.3μM 23656556
SKBR3 Function assay 0.5 uM 18 hrs Inhibition of HSP90 in human SKBR3 cells assessed as aggregation of intracellular HER2 at 0.5 uM after 18 hrs by DAPI staining-based immunofluorescence microscopic analysis 23859777
A549 Cytotoxicity assay 2 days Cytotoxicity against human A549 cells after 2 days by AlamarBlue assay, IC50=0.15μM 23947794
CL1-5 Function assay 2 uM 16 hrs Inhibition of HSP90 in human CL1-5 cells assessed as reduction of total Akt at 2 uM after 16 hrs by Western blotting analysis 24428777
L6 Cytotoxicity assay 72 hrs Cytotoxicity against rat L6 cells after 72 hrs by Alamar Blue assay, IC50=6μM 24580531
Sf9 Function assay 16 hrs Displacement of GM-BODIPY from human full length HSP90 alpha expressed in baculovirus-infected Sf9 cells after 16 hrs by fluorescence polarization assay, IC50=0.074μM 24751441
MDA-kb2 Function assay 18 hrs Inhibition of HSP90 in human MDA-kb2 cells assessed as reduction in glucocorticoid receptor-dependent luciferase expression after 18 hrs by firefly luciferase reporter gene assay, IC50<0.01μM 24984936
MCF7 Antiproliferative assay 72 hrs Antiproliferative activity against human MCF7 cells assessed as growth inhibition after 72 hrs by MTS/PMS assay, IC50=0.04μM 25075762
MDA-MB-231 Cytotoxicity assay 72 hrs Cytotoxicity against human MDA-MB-231 cells after 72 hrs by MTT assay, IC50=0.05μM 25105924
LNCAP Cytotoxicity assay 72 hrs Cytotoxicity against human LNCAP cells after 72 hrs by MTT assay, IC50=0.43μM 25105924
MDA-MB 231 Function assay 0.5 and 5 uM Inhibition of HSP90 in human MDA-MB 231 cells assessed increase in HSP70 protein levels at 0.5 and 5 uM by Western blot method 25105924
HUVEC Cytotoxicity assay 72 hrs Cytotoxicity against HUVEC cells after 72 hrs by MTT assay, IC50=0.019μM 25277067
A431 Cytotoxicity assay 72 hrs Cytotoxicity against human A431 cells after 72 hrs by MTT assay, IC50=0.04μM 25277067
BGC823 Cytotoxicity assay 72 hrs Cytotoxicity against human BGC823 cells after 72 hrs by MTT assay, IC50=0.04μM 25277067
HepG2 Cytotoxicity assay 72 hrs Cytotoxicity against human HepG2 cells after 72 hrs by MTT assay, IC50=0.04μM 25277067
MDA-MB-231 Cytotoxicity assay 72 hrs Cytotoxicity against human MDA-MB-231 cells after 72 hrs by MTT assay, IC50=0.05μM 25277067
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50=0.097μM 25277067
HL7702 Cytotoxicity assay 72 hrs Cytotoxicity against human HL7702 cells after 72 hrs by MTT assay, IC50=0.141μM 25277067
SW480 Cytotoxicity assay 72 hrs Cytotoxicity against human SW480 cells after 72 hrs by MTT assay, IC50=0.31μM 25277067
HeLa Cytotoxicity assay 72 hrs Cytotoxicity against human HeLa cells after 72 hrs by MTT assay, IC50=0.798μM 25277067
MDA-MB 231 Function assay 0.5 uM 24 hrs Inhibition Hsp90 in human MDA-MB 231 cells assessed as increase in HSP70 protein level at 0.5 uM incubated for 24 hrs by Western blot method 25277067
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells assessed as growth inhibition after 72 hrs by MTS/PMS assay, IC50=0.0427μM 25756299
MCF7 Function assay 24 hrs Inhibition of HSP90 in human MCF7 cells assessed as pAkt degradation at 5 times IC50 after 24 hrs by Western blot analysis 25756299
MCF7 Function assay 24 hrs Inhibition of HSP90 in human MCF7 cells assessed as Her2 degradation at 5 times IC50 after 24 hrs by Western blot analysis 25756299
MCF7 Function assay 24 hrs Inhibition of HSP90 in human MCF7 cells assessed as Cdk6 degradation at 5 times IC50 after 24 hrs by Western blot analysis 25756299
MCF7 Function assay 24 hrs Inhibition of HSP90 in human MCF7 cells assessed as Raf degradation at 5 times IC50 after 24 hrs by Western blot analysis 25756299
MCF7 Function assay 24 hrs Change in Cdc37 expression in human MCF7 cells at 5 times IC50 after 24 hrs by Western blot analysis 25756299
MCF7 Function assay 24 hrs Change in p23 expression in human MCF7 cells at 5 times IC50 after 24 hrs by Western blot analysis 25756299
MCF7 Function assay 24 hrs Inhibition of HSP90 in human MCF7 cells assessed as induction of heat shock response-mediated HSP90 production at 5 times IC50 after 24 hrs by Western blot analysis relative to vehicle-treated control 25756299
MCF7 Function assay 24 hrs Inhibition of HSP90 in human MCF7 cells assessed as induction of heat shock response-mediated HSP70 production at 5 times IC50 after 24 hrs by Western blot analysis relative to vehicle-treated control 25756299
MCF7 Function assay 24 hrs Inhibition of HSP90 in human MCF7 cells assessed as induction of heat shock response-mediated HSP27 production at 5 times IC50 after 24 hrs by Western blot analysis relative to vehicle-treated control 25756299
PC12 Function assay 10 uM 3 to 16 hrs Inhibition of D-aspartate biosynthesis in rat PC12 cells assessed as reduction of intracellular D-aspartate content at 10 uM measured at 3 to 16 hrs by O-phthalaldehyde/N-acetyl-L-cysteine derivatization technique-based HPLC analysis relative to vehicle-t 26642769
PC12 Function assay 10 uM 6 to 16 hrs Inhibition of D-aspartate biosynthesis in rat PC12 cells assessed as reduction of total D-aspartate content at 10 uM measured at 6 to 16 hrs by O-phthalaldehyde/N-acetyl-L-cysteine derivatization technique-based HPLC analysis relative to vehicle-treated c 26642769
PC12 Function assay 24 hrs Inhibition of D-aspartate biosynthesis in rat PC12 cells assessed as reduction of intracellular D-aspartate level up to 10 uM after 24 hrs by O-phthalaldehyde/N-acetyl-L-cysteine derivatization technique-based HPLC analysis 26642769
PC12 Function assay up to 10 uM 24 hrs Inhibition of D-aspartate biosynthesis in rat PC12 cells assessed as reduction of D-aspartate level in cell culture medium up to 10 uM after 24 hrs by O-phthalaldehyde/N-acetyl-L-cysteine derivatization technique-based HPLC analysis 26642769
A549 Function assay 12 to 24 hrs Inhibition of Hsp90 in human A549 cells assessed as decrease in EGFR levels at five times IC50 value after 12 to 24 hrs by Western blot analysis 26745854
A549 Function assay 12 to 24 hrs Inhibition of Hsp90 in human A549 cells assessed as decrease in Her2 levels at five times IC50 value after 12 to 24 hrs by Western blot analysis 26745854
A549 Function assay 12 to 24 hrs Inhibition of Hsp90 in human A549 cells assessed as decrease in C-Raf levels at five times IC50 value after 12 to 24 hrs by Western blot analysis 26745854
SKBR3 Function assay Inhibition of Hsp90 in human SKBR3 cells, IC50=0.07μM 26844689
BA/F3 Function assay 48 hrs Inhibition of imatinib-resistant BCR-ABL T315I mutant (unknown origin) expressed in mouse BA/F3 cells assessed as decrease in cell viability after 48 hrs by trypan blue exclusion assay, IC50=1μM 26844689
BA/F3 Function assay 48 hrs Inhibition of imatinib-resistant BCR-ABL E255K mutant (unknown origin) expressed in mouse BA/F3 cells assessed as decrease in cell viability after 48 hrs by trypan blue exclusion assay, IC50=1μM 26844689
BA/F3 Function assay 48 hrs Inhibition of BCR-ABL (unknown origin) expressed in mouse BA/F3 cells assessed as decrease in cell viability after 48 hrs by trypan blue exclusion assay, IC50=5μM 26844689
MDA-MB-231 Antiproliferative assay 72 hrs Antiproliferative activity against human MDA-MB-231 cells after 72 hrs by MTS/PMS assay, Activity=0.06μM 27003516
MDA-MB-231 Antiproliferative assay 72 hrs Antiproliferative activity against human MDA-MB-231 cells after 72 hrs by SRB assay, IC50=0.03μM 27266997
HeLa Antiproliferative assay 72 hrs Antiproliferative activity against human HeLa cells after 72 hrs by SRB assay, IC50=0.06μM 27266997
SNU638 Anticancer assay 72 hrs Anticancer activity against human SNU638 cells measured after 72 hrs by SRB assay, IC50=0.03μM 27283788
Caki1 Anticancer assay 72 hrs Anticancer activity against human Caki1 cells measured after 72 hrs by SRB assay, IC50=0.056μM 27283788
A549 Anticancer assay 72 hrs Anticancer activity against human A549 cells measured after 72 hrs by SRB assay, IC50=0.109μM 27283788
MDA-MB-231 Anticancer assay 72 hrs Anticancer activity against human MDA-MB-231 cells measured after 72 hrs by SRB assay, IC50=0.11μM 27283788
HCT116 Anticancer assay 72 hrs Anticancer activity against human HCT116 cells measured after 72 hrs by SRB assay, IC50=0.15μM 27283788
SKBR3 Antiproliferative assay 1 to 3 days Antiproliferative activity against Her2-overexpressing human SKBR3 cells after 1 to 3 days by MTS assay, GI50=0.43μM 27783977
NCI-H1975 Antiproliferative assay 1 to 3 days Antiproliferative activity against gefitinib-resistant human NCI-H1975 cells after 1 to 3 days by MTS assay, GI50=0.56μM 27783977
RPMI8226 Growth inhibition assay 72 hrs Growth inhibition of human RPMI8226 cells after 72 hrs by MTS/PMS assay, GI50=0.003μM 29057043
MDA-MB-231 Antiproliferative assay 72 hrs Antiproliferative activity against human MDA-MB-231 cells after 72 hrs by SRB assay, IC50=0.06μM 29172085
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by SRB assay, IC50=0.1μM 29172085
NCI-H1975 Antiproliferative assay 72 hrs Antiproliferative activity against human NCI-H1975 cells after 72 hrs by Cell Titer 96 Aqueous One Solution cell proliferation assay, GI50=0.56μM 29202402
A549 Function assay 5 to 10 uM 24 hrs Inhibition of HSP90alpha in human A549 cells assessed as upregulation of HSP90alpha expression at 5 to 10 uM after 24 hrs by Western blot analysis 29486954
A549 Function assay 5 to 10 uM 24 hrs Inhibition of HSP90beta in human A549 cells assessed as upregulation of HSP90beta expression at 5 to 10 uM after 24 hrs by Western blot analysis 29486954
SKBR3 Function assay 24 hrs Inhibition of HSP90 at N-terminus in human SKBR3 cells assessed as induction of Raf1 protein degradation incubated for 24 hrs by Western blot analysis 31591016
SKBR3 Function assay 24 hrs Inhibition of HSP90 at N-terminus in human SKBR3 cells assessed as induction of CDK4 protein degradation incubated for 24 hrs by Western blot analysis 31591016
SKBR3 Function assay 24 hrs Inhibition of HSP90 at N-terminus in human SKBR3 cells assessed as induction of Her2 protein degradation incubated for 24 hrs by Western blot analysis 31591016
SKBR3 Function assay 24 hrs Inhibition of HSP90 at N-terminus in human SKBR3 cells assessed as induction of AKT protein degradation incubated for 24 hrs by Western blot analysis 31591016
Klicka för att visa mer experimentella data för cellinjer

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Molekylvikt 560.64 Formel

C29H40N2O9

 Lagring (från mottagningsdatumet)
CAS-nr 30562-34-6 Ladda ner SDF Lagring av stamlösningar

Synonymer NSC 122750 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

Löslighet (Solubility)

In vitro
Batch:

DMSO : 100 mg/mL (178.36 mM)
(Fuktkontaminerad DMSO kan minska lösligheten. Använd färk, vattenfri DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritetsräknare

Massa Koncentration Volym Molekylvikt
Utspädningsräknare Molekylviktsräknare

In vivo
Batch:

In vivo-formuleringsräknare (Klar lösning)

Steg 1: Ange information nedan (Rekommenderas: Ett extra djur för att ta hänsyn till förluster under experimentet)

mg/kg g μL

Steg 2: Ange in vivo-formuleringen (Detta är endast räknaren, inte formuleringen. Vänligen kontakta oss först om det inte finns någon in vivo-formulering i löslighetsavsnittet.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Beräkningsresultat:

Arbetskoncentration: mg/ml;

Metod för att bereda DMSO-stamlösning: mg substans förlöst i μL DMSO ( Stamlösningskoncentration mg/mL, Vänligen kontakta oss först om koncentrationen överskrider DMSO-lösligheten för denna batch av substansen. )

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedanμL PEG300, blanda och klarna, tillsätt sedanμL Tween 80, blanda och klarna, tillsätt sedan μL ddH2O, blanda och klarna.

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedan μL Majsolja, blanda och klarna.

Obs: 1. Se till att vätskan är klar innan du tillsätter nästa lösningsmedel.
2. Se till att tillsätta lösningsmedlet/lösningsmedlen i ordning. Du måste se till att lösningen som erhålls i föregående tillsats är en klar lösning innan du fortsätter att tillsätta nästa lösningsmedel. Fysiska metoder som vortex, ultraljud eller varmt vattenbad kan användas för att underlätta upplösningen.

Verkningsmekanism (Mechanism of Action)

Targets/IC50/Ki
p185
(SKBr3 cells)
70 nM
HSP90 (N-terminal domain)
(Cell-free assay)
0.78 μM(Kd)
HSP90
(Cell-free assay)
1.2 μM(Kd)
In vitro
Geldanamycin binds in the ATP-binding site in the N-terminus domain of Hsp90s (residues 1-220). This compound inhibits the ATPase activity of Hsp90 in a dose-dependent manner. It 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. This chemical causes polyubiquitination and proteasomal degradation of the p185 receptor protein-tyrosin kinase and shows a IC50 with 70 nM. It is a typical anti-tumor reagent, shows a mean GI50 with 0.18 μM against the panel of 60 human tumor cell lines.
Kinasanalys
Isothermal Titration Calorimetry (ITC) of Nucelotide Binding
Titreringsexperimenten utförs med MSC-systemet. I varje experiment injiceras 16 alikvoter om 15 μL geldanamycin (300 μM i 1 % DMSO) i 1,3 mL protein (31 μM i 20 mM Tris-HCl, pH 7,5, 1 mM EDTA) vid 25 °C, och de resulterande data anpassas efter att ha subtraherat utspädningsvärmen. Utspädningsvärmen bestäms i separata experiment från tillsats av denna förening till buffert och buffert till protein. Inga bevis för bindning av DMSO i nukleotidbindningsstället observeras. Titreringsdata anpassas med en icke-linjär algoritm för kurvanpassning med minsta kvadrat med tre flytande variabler: stökiometri, bindningskonstant (Kb) 1/Kd) och ändring av entalpin för interaktion (ΔH°). Dissociationskonstanterna uppskattade för denna förenings bindning till intakt jäst-Hsp90 är 1,22 μM, och för bindning till Hsp90 N-terminala domän är 0,78 μM. Ingen meningsfull värme observeras vid bindning till C-terminala fragmentet.
In vivo
Geldanamycin (50 mg//kg) shows 30% inhibition on pl85-associated phosphotyrosine levels in FRE/erbB-2 mice.
Referenser
  • [4] https://pubmed.ncbi.nlm.nih.gov/7909494/
  • [5] https://pubmed.ncbi.nlm.nih.gov/7628050/
  • [6] https://pubmed.ncbi.nlm.nih.gov/7562911/

Klinisk prövningsinformation (Clinical Trial Information)

(data från https://clinicaltrials.gov, uppdaterad den 2024-05-22)

NCT-nummer Rekrytering Tillstånd Sponsor/Samarbetspartners Startdatum Faser
NCT00003969 Completed
Unspecified Adult Solid Tumor Protocol Specific
Cancer Research UK|National Cancer Institute (NCI)
 August 1998 Phase 1