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

nur für Forschungszwecke

Geldanamycin (NSC 122750) HSP90-Inhibitor

Kat.-Nr.S2713

Geldanamycin ist ein natürlich vorkommender HSP90-Inhibitor mit einem Kd von 1,2 μM, der die Assoziation von Glucocorticoidrezeptor (GR)/HSP spezifisch stört. Geldanamycin lindert virusinfektionsbedingte ALI (akute Lungenverletzung)/ARDS (akutes Atemnotsyndrom), indem es die Entzündungsreaktionen des Wirts reduziert.
Geldanamycin (NSC 122750) Antineoplastic and Immunosuppressive Antibiotics Inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 560.64

Springe zu

Qualitätskontrolle

Charge: Reinheit: 99.96%
99.96

Zellkultur, Behandlung & Arbeitskonzentration

Zelllinien Assay-Typ Konzentration Inkubationszeit Formulierung Aktivitätsbeschreibung 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
Klicken Sie hier, um weitere experimentelle Daten zu Zelllinien anzuzeigen

Chemische Informationen, Lagerung & Stabilität

Molekulargewicht 560.64 Formel

C29H40N2O9

 Lagerung (Ab dem Eingangsdatum)
CAS-Nr. 30562-34-6 SDF herunterladen Lagerung von Stammlösungen

Synonyme 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

Löslichkeit

In vitro
Charge:

DMSO : 100 mg/mL (178.36 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritätsrechner

Masse Konzentration Volumen Molekulargewicht
Verdünnungsrechner Molekulargewichtsrechner

In vivo
Charge:

In-vivo-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie die untenstehenden Informationen ein (Empfohlen: Ein zusätzliches Tier zur Berücksichtigung von Verlusten während des Experiments)

mg/kg g μL

Schritt 2: Geben Sie die In-vivo-Formulierung ein (Dies ist nur der Rechner, keine Formulierung. Bitte kontaktieren Sie uns zuerst, wenn es im Abschnitt "Löslichkeit" keine In-vivo-Formulierung gibt.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

Methode zur Herstellung der DMSO-Stammlösung: mg Wirkstoff vorgelöst in μL DMSO ( Konzentration der Stammlösung mg/mL, Bitte kontaktieren Sie uns zuerst, wenn die Konzentration die DMSO-Löslichkeit der Wirkstoffcharge überschreitet. )

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügenμL PEG300, mischen und klären, dann hinzufügenμL Tween 80, mischen und klären, dann hinzufügen μL ddH2O, mischen und klären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügen μL Maisöl, mischen und klären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, das/die Lösungsmittel der Reihe nach hinzuzufügen. Sie müssen sicherstellen, dass die bei der vorherigen Zugabe erhaltene Lösung eine klare Lösung ist, bevor Sie mit der Zugabe des nächsten Lösungsmittels fortfahren. Physikalische Methoden wie Vortex, Ultraschall oder ein heißes Wasserbad können zur Unterstützung des Lösens verwendet werden.

Wirkmechanismus

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 bindet in der ATP-Bindungsstelle in der N-terminalen Domäne von Hsp90 (Reste 1-220). Diese Verbindung hemmt die ATPase-Aktivität von Hsp90 dosisabhängig. Sie verursacht einen dosisabhängigen G2-Arrest und eine reversible Hemmung des Eintritts in die S-Phase in der menschlichen Ovarialzelllinie A2780. Diese Hemmung geht mit einem p53-Anstieg einher und ist schließlich als p53-abhängig nachgewiesen. Diese Chemikalie verursacht eine Polyubiquitinierung und proteasomale Degradation des p185-Rezeptor-Protein-Tyrosin-Kinase und zeigt eine IC50 von 70 nM. Es ist ein typisches Antitumor-Reagenz und zeigt eine mittlere GI50 von 0,18 μM gegen das Panel von 60 menschlichen Tumorzelllinien.
Kinase-Assay
Isotherme Titrationskalorimetrie (ITC) der Nukleotidbindung
Die Titrationsexperimente werden mit dem MSC-System durchgeführt. In jedem Experiment werden 16 Aliquots von 15 μL Geldanamycin (300 μM in 1% DMSO) in 1,3 mL Protein (31 μM in 20 mM Tris-HCl, pH 7,5, 1 mM EDTA) bei 25 °C injiziert, und die resultierenden Daten werden nach Subtraktion der Verdünnungswärmen angepasst. Die Verdünnungswärmen werden in separaten Experimenten durch Zugabe dieser Verbindung zu Puffer und Puffer zu Protein bestimmt. Es gibt keinen Hinweis auf eine Bindung von DMSO in der Nukleotidbindungsstelle. Die Titrationsdaten werden mit einem nichtlinearen Kleinste-Quadrate-Kurvenanpassungsalgorithmus mit drei gleitenden Variablen angepasst: Stöchiometrie, Bindungskonstante (Kb) 1/Kd) und Enthalpieänderung der Wechselwirkung (ΔH°). Die geschätzten Dissoziationskonstanten für die Bindung dieser Verbindung an intaktes Hsp90 aus Hefe betragen 1,22 μM und für die Bindung an die N-terminale Domäne von Hsp90 0,78 μM. Bei der Bindung an das C-terminale Fragment wird keine signifikante Wärme beobachtet.
In vivo
Geldanamycin (50 mg/kg) zeigt eine 30%ige Hemmung der p185-assoziierten Phosphotyrosinspiegel bei FRE/erbB-2-Mäusen.
Literatur
  • [4] https://pubmed.ncbi.nlm.nih.gov/7909494/
  • [5] https://pubmed.ncbi.nlm.nih.gov/7628050/
  • [6] https://pubmed.ncbi.nlm.nih.gov/7562911/

Klinische Studieninformationen

(Daten von https://clinicaltrials.gov, aktualisiert am 2024-05-22)

NCT-Nummer Rekrutierung Erkrankungen Sponsor/Kooperationspartner Startdatum Phasen
NCT00003969 Completed
Unspecified Adult Solid Tumor Protocol Specific
Cancer Research UK|National Cancer Institute (NCI)
 August 1998 Phase 1

Technischer Support

Handhabungshinweise

Tel: +1-832-582-8158 Ext:3

Wenn Sie weitere Fragen haben, hinterlassen Sie bitte eine Nachricht.

Bitte geben Sie Ihren Namen ein.
Bitte geben Sie Ihre E-Mail-Adresse ein. Bitte geben Sie eine gültige E-Mail-Adresse ein.
Bitte schreiben Sie uns etwas.