Home Metabolism Dehydrogenase Inhibitor Tetraethylthiuram disulfide (Disulfiram)

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Tetraethylthiuram disulfide (Disulfiram) ALDH-Inhibitor

Kat.-Nr.: S1680

Disulfiram ist ein spezifischer Inhibitor der Aldehyd-Dehydrogenase (ALDH) mit einer IC50 von 0,15 μM und 1,45 μM für hALDH1 bzw. hALDH2. Disulfiram wird zur Behandlung des chronischen Alkoholismus eingesetzt, indem es eine akute Empfindlichkeit gegenüber Alkohol hervorruft. Disulfiram induziert Apoptose. Disulfiram ist auch ein Inhibitor der Porenbildung durch Gasdermin D (GSDMD).
Tetraethylthiuram disulfide (Disulfiram) Dehydrogenase Inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 296.54

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Qualitätskontrolle (Quality Control)

Charge: Reinheit: 99.91%
99.91

Zellkultur, Behandlung & Arbeitskonzentration
(Cell Culture, Treatment & Working Concentration)

Zelllinien Assay-Typ Konzentration Inkubationszeit Formulierung Aktivitätsbeschreibung PMID
insect cells Function assay 30 mins Inhibition of recombinant human LOXL4 expressed in baculovirus infected insect cells using diaminopentane as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorimetric method, IC50 = 0.059 μM. 30098867
CHO Function assay 30 mins Inhibition of recombinant human LOXL3 expressed in CHO cells using diaminopentane as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorimetric method, IC50 = 0.093 μM. 30098867
MCF7 Antiproliferative assay 72 hrs Antiproliferative activity against human MCF7 cells expressing BCA2 and estrogen receptor after 72 hrs by MTT assay, IC50 = 0.1 μM. 20222671
NS0 Function assay 30 mins Inhibition of recombinant LOXL2 (unknown origin) expressed in NS0 cells using diaminopentane as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorimetric method, IC50 = 0.15 μM. 30098867
T47D Antiproliferative assay 72 hrs Antiproliferative activity against human T47D cells expressing BCA2 and estrogen receptor after 72 hrs by MTT assay, IC50 = 0.17 μM. 20222671
MDA-MB-231 Antiproliferative assay 72 hrs Antiproliferative activity against human MDA-MB-231 cells expressing BCA2 and ERalpha after 72 hrs by MTT assay, IC50 = 0.32 μM. 20222671
HEK293 Function assay 30 mins Inhibition of recombinant human LOX expressed in HEK293 cells using diaminopentane as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorimetric method, IC50 = 0.32 μM. 30098867
CHO Function assay Agonist activity at human TRPA1 channel expressed in CHO cells assessed as increase in intracellular calcium levels, EC50 = 3 μM. 20356305
CEM-SS Antiviral assay Antiviral activity against HIV-1 in CEM-SS cells using XXT assay, IC50 = 3.9 μM. 9207937
MCF10A Antiproliferative assay 72 hrs Antiproliferative activity against human MCF10A cells after 72 hrs by MTT assay, IC50 = 10 μM. 20222671
HepG2 Cytotoxicity assay 72 hrs Cytotoxicity against human HepG2 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50 = 38 μM. 29571571
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
fibroblast cells qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells 29435139
Klicken Sie hier, um weitere experimentelle Zellliniendaten anzuzeigen

Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Molekulargewicht 296.54 Formel

C10H20N2S4

 Lagerung (Ab Erhaltdatum)
CAS-Nr. 97-77-8 SDF herunterladen Lagerung von Stammlösungen

Synonyme NSC 190940, Tetraethylthiuram disulfide, TETD Smiles CCN(CC)C(=S)SSC(=S)N(CC)CC

Löslichkeit (Solubility)

In vitro
Charge:

DMSO : 59 mg/mL (198.96 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 59 mg/mL

Water : Insoluble

Molaritätsrechner

Masse Konzentration Volumen Molekulargewicht
Verdünnungsrechner Molekulargewicht-Rechner

In vivo
Charge:

In-vivo-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie unten die Informationen ein (Empfohlen: Ein zusätzliches Tier einplanen, um Verluste während des Experiments auszugleichen)

mg/kg g μL

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

% DMSO % % Tween 80 % ddH2O
%DMSO %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

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

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammflüssigkeit, fügen Sie als Nächstes hinzuμL PEG300, mischen und aufklären, fügen Sie als Nächstes hinzuμL Tween 80, mischen und aufklären, fügen Sie als Nächstes hinzu μL ddH2O, mischen und aufklären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammflüssigkeit, fügen Sie als Nächstes hinzu μL Maisöl, mischen und aufklären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, die Lösungsmittel in der richtigen Reihenfolge hinzuzufügen. Sie müssen sicherstellen, dass die im vorherigen Schritt erhaltene Lösung klar ist, bevor Sie das nächste Lösungsmittel hinzufügen. Physikalische Methoden wie Vortexen, Ultraschall oder ein warmes Wasserbad können zur Unterstützung des Lösungsvorgangs verwendet werden.

Wirkungsmechanismus (Mechanism of Action)

Targets/IC50/Ki
ALDH1
(Cell-free assay)
0.15 μM
ALDH2
(Cell-free assay)
1.45 μM
In vitro

Disulfiram-copper complex potently inhibits the proteasomal activity in cultured breast cancer MDA-MB-231 and MCF10DCIS.com cells, but not normal, immortalized MCF-10A cells, before induction of apoptotic cancer cell death.

This compound (DS), a clinically used anti-alcoholism drug, strongly inhibits constitutive and 5-FU-induced NF-kappaB activity in a dose-dependent manner. It inhibits both NF-kappaB nuclear translocation and DNA binding activity but has no effect on 5-FU-induced IkappaBalpha degradation. This chemical significantly enhances the apoptotic effect of 5-FU on DLD-1 and RKO(WT) cell lines and synergistically potentiated the cytotoxicity of 5-FU to both cell lines. It also effectively abolishes 5-FU chemoresistance in a 5-FU resistant cell line H630(5-FU) in vitro.

Oseltamivir decreases the number of viable cells, and the addition of CuCl(2) significantly enhances the DSF-induced cell death to less than 10% of control.

This compound given to melanoma cells in combination with Cu2+ or Zn2+ decreases expression of cyclin A and reduces proliferation in vitro at lower concentrations than disulfiram alone.

In vivo

Disulfiram significantly inhibits the tumor growth (by 74%), associated with in vivo proteasome inhibition (as measured by decreased levels of tumor tissue proteasome activity and accumulation of ubiquitinated proteins and natural proteasome substrates p27 and Bax) and apoptosis induction (as shown by caspase activation and apoptotic nuclei formation) in mice bearing MDA-MB-231 tumor xenografts.

This compound blocks the P-glycoprotein extrusion pump, inhibits the transcription factor nuclear factor-kappaB, sensitizes tumors to chemotherapy, reduces angiogenesis, and inhibits tumor growth in mice. It inhibits growth and angiogenesis in melanomas transplanted in severe combined immunodeficient mice, and these effects are potentiated by Zn2+ supplementation.

Referenzen
  • [4] https://pubmed.ncbi.nlm.nih.gov/15367699/
  • [5] https://pubmed.ncbi.nlm.nih.gov/9354647/
  • [6] https://pubmed.ncbi.nlm.nih.gov/32367036/

Informationen zu klinischen Studien (Clinical Trial Information)

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

NCT-Nummer Rekrutierung Bedingungen Sponsor/Kollaboratoren Startdatum Phases
NCT05626920 Recruiting
Inherited Retinal Dystrophy Primarily Involving Sensory Retina
University of Washington
 December 2023 Phase 1|Phase 2
NCT04485130 Terminated
Covid19
University of California San Francisco
 August 18 2021 Phase 2
NCT03151772 Terminated
Glioblastoma
Sahlgrenska University Hospital Sweden
 January 29 2018 Early Phase 1
NCT02309801 Completed
Healthy
Parc de Salut Mar|Ministerio de Sanidad Servicios Sociales e Igualdad
 July 2012 Phase 1