Home Autophagy Autophagy Hämmare HCQ (Hydroxychloroquine) Sulfate

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HCQ (Hydroxychloroquine) Sulfate Autophagy Hämmare

Kat.nr.: S4430

Hydroxychloroquine (HCQ) Sulfate är ett antimalariamedel som används för behandling av systemisk lupus erythematosus, reumatoid artrit och andra autoimmuna, inflammatoriska och dermatologiska tillstånd. Verkar även som en hämmare av autophagy och toll-like receptor (TLR) 7/9.
HCQ (Hydroxychloroquine) Sulfate Autophagy Hämmare Chemical Structure

Kemisk struktur

Molekylvikt: 433.95

Hoppa till

Kvalitetskontroll (Quality Control)

Batch: Renhet: 99.86%
99.86

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

Cellinjer Analystyp Koncentration Inkubationstid Formulering Aktivitetsbeskrivning PMID
Function assay HEK-Blue cells Antagonist activity at human TLR9 expressed in HEK-Blue cells assessed as reduction in CpGB-induced NF-kappaB levels after 24 hrs by spectrophotometric analysis, IC50 = 0.11 μM. 30292896
Antiviral assay Vero E6 cells 48 h IC50 for antiviral activity against SARS-CoV-2 in the Vero E6 cell line at 48 h by immunofluorescence-based assay (detecting the viral NP protein in the nucleus of the Vero E6 cells)., IC50 = 0.67608 μM. 32353859
Function assay HEK-Blue cells Antagonist activity at human TLR7 expressed in HEK-Blue cells assessed as reduction in CL264-induced NF-kappaB levels after 24 hrs by spectrophotometric analysis, IC50 = 0.8 μM. 30292896
Function assay HEK293 cells hERG binding assays: Displacement of [3H]-Dofetilide (5 nM final) from hERG membranes obtained from HEK293 cells, Ki = 2.51189 μM. 32353859
Antiviral assay Vero E6 cells IC90 for antiviral activity against SARS-CoV-2 in the Vero E6 cell line by measuring infectious viral titer of supernatent from compound-treated Vero E6 cells by Median Tissue Culture Infectious Dose (TCID)50 by the method of Reed and Muench, IC90 = 5.78 μM. 32353859
Antiproliferative assay BxPC3 cells 72 hrs Antiproliferative activity against human BxPC3 cells after 72 hrs by SRB method, IC50 = 33 μM. 25699157
qHTS assay A673 cells qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
qHTS assay BT-37 cells qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
qHTS assay SK-N-MC cells qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
qHTS assay NB-EBc1 cells qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
qHTS assay LAN-5 cells qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Antiproliferative assay A549 cells 25 ug/ml 20 hrs Antiproliferative activity in human A549 cells at 25 ug/ml up to 20 hrs by xCELLigence RTCA SP based cellular impedance analysis 28570977
Antiproliferative assay A549 cells 25 ug/ml 60 hrs Antiproliferative activity in human A549 cells at 25 ug/ml after 60 hrs by xCELLigence RTCA SP based cellular impedance analysis 28570977
Autophagy assay NCI-H3122 cells 25 to 50 uM 6 hrs Inhibition of autophagy in human NCI-H3122 cells assessed as increase in punctate LC3 expression at 25 to 50 uM after 6 hrs by fluorescence microscopic analysis 25699157
Apoptosis assay H460 cells 25 to 75 uM 24 hrs Induction of apoptosis in human H460 cells at 25 to 75 uM after 24 hrs by annexin-V staining-based flow cytometry 25699157
Autophagy assay H460 cells 24 hrs Inhibition of autophagy in human H460 cells assessed as increase in LC3-2 level at IC50 after 24 hrs by immunoblot analysis 25699157
Antiviral assay Vero E6 cells 2 days Antiviral efficacy against SARS-CoV-2 (strain BavPat1) in Vero E6 cells assessed by inhibition of viral RNA replication measured by RT-PCR after 2 days, EC50 = 4.17 μM. ChEMBL
Antiviral assay Vero E6 cells 3 days IC50 determination at MOI 0.004 using CellTiter- Glo (CTG) assay, performed 3 days post-infection in SARS-CoV-2 infected Vero E6 cells, IC50 = 9.21 μM. ChEMBL
Antiviral assay Vero E6 cells 3 days IC50 determination at MOI 0.01 using CellTiter- Glo (CTG) assay, performed 3 days post-infection in SARS-CoV-2 infected Vero E6 cells, IC50 = 11.17 μM. ChEMBL
Antiviral assay Vero E6 cells 2 days Antiviral efficacy against SARS-CoV-2 (strain BavPat1) in Vero E6 cells assessed by inhibition of viral RNA replication measured by RT-PCR after 2 days, EC90 = 25.49 μM. ChEMBL
Klicka för att visa mer experimentella data för cellinjer

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

Molekylvikt 433.95 Formel

C18H28ClN3O5S

 Lagring (från mottagningsdatumet)
CAS-nr 747-36-4 Ladda ner SDF Lagring av stamlösningar

Synonymer NSC 4375 Smiles CCN(CCCC(C)NC1=C2C=CC(=CC2=NC=C1)Cl)CCO.OS(=O)(=O)O

Löslighet (Solubility)

In vitro
Batch:

Water : 87 mg/mL

DMSO : Insoluble
(Fuktkontaminerad DMSO kan minska lösligheten. Använd färk, vattenfri DMSO.)

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
TLR9
Autophagy
In vitro

Hydroxychloroquine Sulfate is a potent inhibitor of autophagy. It prevents lysosomal acidification, thereby interfering with a key step in the autophagic process.HCQ treatment inhibits RCC (renal cell cancer) cell growth, promotes apoptosis, inhibits mitochondrial oxygen consumption, and increases rates of glycolysis.
Kinasanalys
In vitro kinasanalyser
Med renat protein inkuberas rekombinant S6-protein och rekombinant aktivt P70S6K i 1x kinasbuffert med varierande mängder HCQ eller RAD001 i närvaro (25 μM) eller frånvaro av ATP i 30 minuter vid 30°C. Totalt och fosforylerat S6 vid ser235/236 och ser240/244 detekteras genom westernanalys med användning av fosfospecifika antikroppar. Notera att rekombinant GST-taggat S6 (53 kd) särskiljs från endogent S6 (32 kd) på western blot.
In vivo

The treatment of Hydroxychloroquine Sulfate reduces the infarct size in an in vivo rat model of I/R injury and the cardioprotective effect of Hydroxychloroquine is ERK1/2 dependent.

In addition, Hydroxychloroquine Sulfate shows an early vascular protective effect. HCQ seems to prevent the occurrence of endothelial dysfunction(ED) in treated animals.
Referenser
  • [4] http://acrabstracts.org/abstract/effects-of-in-vivo-treatment-with-hydroxychloroquine-on-endothelial-function-in-a-murine-model-of-systemic-lupus-erythematosus/
  • [5] https://pubmed.ncbi.nlm.nih.gov/24342772/

Applikationer (Applications)

Metoder Biomarkörer Bilder PMID
Western blot NOX2 / β-actin p-NF-κB / β-actin NLRP3 / β-actin p62 / LC3-I / LC3-II / GAPDH
S4430-WB-1
32260307
IHC HE staining of spleen tissue
S4430-IHC-2
29456648
Immunofluorescence ZO-1
S4430-IF-1
32260307

Klinisk prövningsinformation (Clinical Trial Information)

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

NCT-nummer Rekrytering Tillstånd Sponsor/Samarbetspartners Startdatum Faser
NCT06408298 Not yet recruiting
Resectable Localized Prostate Cancer
Lionel.D.Lewis MD|Dartmouth Cancer Center|Dartmouth-Hitchcock Medical Center
 June 2024 Early Phase 1
NCT05841758 Not yet recruiting
Sarcoidosis Pulmonary
Hospices Civils de Lyon
 April 1 2024 Phase 4
NCT04731051 Withdrawn
2019 Novel Coronavirus
King Hussein Cancer Center|Amman Pharmaceutical Industries (API)|Sana Pharmaceutical Industry|ACDIMA Biocenter
 October 2022 Phase 1|Phase 2
NCT05733897 Recruiting
Nonalcoholic Steatohepatitis
National Taiwan University Hospital|National Taiwan University
 June 10 2022 --
NCT05237843 Unknown status
Recurrent Pregnancy Loss
Ain Shams University
 March 1 2022 Phase 1