Home JAK/STAT JAK Inhibitor Tofacitinib (CP-690550)

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Tofacitinib (CP-690550) JAK Inhibitor

Kat.-Nr.S2789

Tofacitinib ist ein neuartiger Inhibitor von JAK3 mit einer IC50 von 1 nM in zellfreien Assays, 20- bis 100-fach weniger potent gegen JAK2 und JAK1. Diese Verbindung hemmt die Expression von antiapoptotischem BCL-A1 und BCL-XL in menschlichen plasmazytoiden dendritischen Zellen (PDC) und induziert die PDC-Apoptose.
Tofacitinib (CP-690550) JAK Inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 312.37

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Qualitätskontrolle

Charge: Reinheit: 99.95%
99.95

Zellkultur, Behandlung & Arbeitskonzentration

Zelllinien Assay-Typ Konzentration Inkubationszeit Formulierung Aktivitätsbeschreibung PMID
T cells Function Assay 0.1/0.3/1 μM 24 h disrupts γc-chain cytokine signaling 21383241
CD4+ T  Function Assay 100 nM 24/48 h abrogates CD3-induced phosphorylation of STATs 21884580
CD4+ T  Growth Inhibition Assay 100/500 nM 48 h inhibits anti-CD3-induced CD4+ T cell proliferation 21884580
CD4+ T  Function Assay 20/100/500 nM 48 h inhibits the levels of IL-4, IFN-γ, IL-17A and IL-22 21884580
Sf9 Function assay 30 mins Inhibition of human GST-fused JAK3 catalytic domain expressed in baculovirus-infected Sf9 cells using polyglutamic acid-tyrosine as substrate after 30 mins by ELISA, Ki = 0.0004 μM. 23668484
Sf9 Function assay 90 mins Inhibition of human recombinant N-terminal GST-tagged JAK3 expressed in Sf9 cells using Biotin-LC-EQEDEPEGDYFEWLE as substrate after 90 mins by TR-FRET assay, IC50 = 0.0006 μM. 22087750
Sf9 Function assay 30 mins Inhibition of human GST-fused JAK1 catalytic domain expressed in baculovirus-infected Sf9 cells using polyglutamic acid-tyrosine as substrate after 30 mins by ELISA, Ki = 0.0007 μM. 23668484
Sf9 Function assay 30 mins Inhibition of human GST-fused JAK2 catalytic domain expressed in baculovirus-infected Sf9 cells using polyglutamic acid-tyrosine as substrate after 30 mins by ELISA, Ki = 0.0007 μM. 23668484
Sf9 Function assay Inhibition of human recombinant GST-tagged JH1 domain (785 to1125) of JAK3 expressed in insect Sf9 cells by ELISA, IC50 = 0.001 μM. 14593182
Sf9 Function assay Inhibition of GST-tagged human JAK3 catalytic domain expressed in Sf9 cells by ELISA, IC50 = 0.001 μM. 21105711
Sf9 Function assay 90 mins Inhibition of human recombinant N-terminal GST-tagged JAK1 expressed in Sf9 cells using Biotin-LC-EQEDEPEGDYFEWLE as substrate after 90 mins by TR-FRET assay, IC50 = 0.003 μM. 22087750
Sf9 Function assay Inhibition of GST-tagged human JAK3 catalytic domain expressed in Sf9 cells by ELISA, IC50 = 0.0033 μM. 21105711
Sf9 Function assay 90 mins Inhibition of human recombinant N-terminal GST-tagged JAK2 expressed in Sf9 cells using Biotin-LC-EQEDEPEGDYFEWLE as substrate after 90 mins by TR-FRET assay, IC50 = 0.004 μM. 22087750
SF21 Function assay 10 mins Inhibition of JAK2 (unknown origin) expressed in SF21 cells using Biotin-KAIETDKEYYTVKD as substrate and [33Pgamma]ATP incubated for 10 mins prior to substrate addition measured after 30 mins by Topcount analysis, IC50 = 0.004 μM. 23541670
insect cells Function assay Inhibition of GST-tagged Jak1 expressed in insect cells using 70 uM ATP, IC50 = 0.0061 μM. 21155605
insect cells Function assay Inhibition of GST-tagged Jak3 expressed in insect cells using 18 uM ATP, IC50 = 0.008 μM. 21155605
T-cells Function assay 72 hrs Inhibition of IL2-induced proliferation of human T cells assessed as [3H]thymidine incorporation after 72 hrs by scintillation counting, IC50 = 0.011 μM. 14593182
insect cells Function assay Inhibition of GST-tagged Jak2 expressed in insect cells using 20 uM ATP, IC50 = 0.012 μM. 21155605
MO7 Function assay Inhibition of Jak3-mediated IL15-induced Stat5 phosphorylation in human MO7 cells by cell-based assay, IC50 = 0.024 μM. 21155605
Ba/F3 Function assay 60 mins Inhibition of TEL-fused JAK1 expressed in Ba/F3 cells assessed as inhibition of STAT5 phosphorylation after 60 mins by AlphaScreen assay, IC50 = 0.026 μM. 22087750
T-cells Function assay Inhibition of JAK3/1 in human T cells expressing CD3 assessed as inhibition of IL2-stimulated STAT5a phosphorylation, IC50 = 0.028 μM. 23540648
PBMC Function assay Inhibition IL-7-indcued STAT5 phosphorylation in human PBMC cells by flow cytometry, IC50 = 0.039 μM. 26927423
TF1 Function assay 20 mins Inhibition of JAK1 in human TF1 cells assessed as inhibition of IL6-induced STAT3 phosphorylation incubated for 20 mins followed by IL6 challenge for 30 mins in presence of whole blood, EC50 = 0.043 μM. 23659214
TF1 Function assay Inhibition of JAK1 in human TF1 cells assessed as suppression of IL6-stimulated STAT3 phosphorylation by AlphaScreen assay, INH = 0.045 μM. 26372653
CTLL Function assay Inhibition of Jak3-mediated IL2-induced Stat5 phosphorylation in mouse CTLL cells by cell-based assay, IC50 = 0.048 μM. 21155605
Sf9 Function assay 90 mins Inhibition of human recombinant N-terminal GST-tagged TYK2 expressed in Sf9 cells using Biotin-LC-EQEDEPEGDYFEWLE as substrate after 90 mins by TR-FRET assay, IC50 = 0.052 μM. 22087750
TF1 Function assay Inhibition of JAK1 in human TF1 cells assessed as inhibition of IL2-induced STAT3 phosphorylation, EC50 = 0.053 μM. 22591402
TF1 Function assay 20 mins Inhibition of JAK1 in human TF1 cells assessed as inhibition of IL6-induced STAT3 phosphorylation incubated for 20 mins prior to IL6-induction measured after 30 to 45 mins, EC50 = 0.053 μM. 22698084
TF1 Function assay 20 mins Inhibition of JAK1 in human TF1 cells assessed as inhibition of IL6-induced STAT3 phosphorylation incubated for 20 mins followed by IL6 challenge for 30 mins, EC50 = 0.053 μM. 23659214
Ba/F3 Function assay 60 mins Inhibition of TEL-fused JAK3 expressed in Ba/F3 cells assessed as inhibition of STAT5 phosphorylation after 60 mins by AlphaScreen assay, IC50 = 0.054 μM. 22087750
T-cells Function assay Inhibition of allogenic cells-stimulated proliferation in monkey T cells by mixed lymphocyte reaction method, IC50 = 0.057 μM. 14593182
CD34+ Function assay Inhibition of JAK2 in human CD34+ cells assessed as inhibition of EPO-mediated cell proliferation, IC50 = 0.071 μM. 26927423
TF1 Function assay Inhibition of IL4-induced proliferation of TF1 cells, IC50 = 0.08 μM. 16934457
T-cells Function assay Inhibition of allogenic cells-stimulated proliferation in human T cells by mixed lymphocyte reaction method, IC50 = 0.087 μM. 14593182
TF1 Function assay 20 mins Inhibition of JAK2 in human TF1 cells assessed as inhibition of EPO-induced STAT5 phosphorylation incubated for 20 mins prior to EPO-induction measured after 30 to 45 mins, EC50 = 0.093 μM. 22698084
TF1 Function assay 20 mins Inhibition of JAK2 in human TF1 cells assessed as inhibition of EPO-induced STAT5 phosphorylation incubated for 20 mins followed by IL6 challenge for 30 mins, EC50 = 0.093 μM. 23659214
PBMC Function assay Inhibition of JAK1 in human PBMC cells assessed as inhibition of IL-6-induced MCP1 secretion, IC50 = 0.095 μM. 26927423
TF1 Function assay 2 hrs Inhibition of JAK2 in GMCSF-stimulated human TF1 cells assessed as suppression of STAT5 phosphorylation preincubated for 2 hrs followed by GMCSF stimulation for 50 mins by FACS reader analysis, IC50 = 0.095 μM. 27130359
TF1 Function assay Inhibition of JAK2 in EPO-stimulated human TF1 cells expressing stably integrated beta-lactamase reporter gene under control of STAT5 response elements in interferon regulatory factor 1 gene promoter by fluorescence assay, IC50 = 0.107 μM. 29156136
Sf9 Function assay Inhibition of GST-tagged human JAK1 catalytic domain expressed in Sf9 cells by ELISA, IC50 = 0.11 μM. 21105711
T-cells Function assay Inhibition of allogenic cells-stimulated proliferation in mouse T cells by mixed lymphocyte reaction method, IC50 = 0.115 μM. 14593182
ME180 Function assay Inhibition of JAK1 in IL6-stimulated human ME180 cells expressing stably integrated beta-lactamase reporter gene under control of sis-inducible element by fluorescence assay, IC50 = 0.124 μM. 29156136
CTLL-2 Antiproliferative assay 72 hrs Antiproliferative activity against IL-2-stimulated mouse CTLL-2 cells expressing JAK1/JAK3 after 72 hrs by alamar blue assay, IC50 = 0.132 μM. 19762238
HT2 Function assay Inhibition of JAK3 in mouse HT2 cells assessed as suppression of cell growth, IC50 = 0.156 μM. 27771180
DND/L12 Function assay 30 mins Inhibition of JAK3 in human DND/L12 cells after 30 mins by luciferase assay in presence of human serum albumin, IC90 = 0.16 μM. 14593182
T-cells Function assay Inhibition of JAK2/1 in human T cells expressing CD3 assessed as inhibition of IFNgamma-stimulated STAT1 phosphorylation, IC50 = 0.17 μM. 23540648
insect Function assay Inhibition of GST-tagged Tyk2 expressed in insect cells using 35 uM ATP, IC50 = 0.176 μM. 21155605
Ba/F3 Function assay 60 mins Inhibition of TEL-fused JAK2 expressed in Ba/F3 cells assessed as inhibition of STAT5 phosphorylation after 60 mins by AlphaScreen assay, IC50 = 0.265 μM. 22087750
TF1 Function assay Inhibition of JAK2 in human TF1 cells assessed as suppression of cell growth, IC50 = 0.2751 μM. 27771180
CD34+ Function assay Inhibition of JAK2 homodimer in human CD34+ cells spiked into human whole blood assessed as inhibition of EPO-induced STAT-5 phosphorylation preincubated for 45 mins followed by EPO addition measured after 15 mins by FACS analysis, IC50 = 0.302 μM. 24417533
HUO3 Function assay 4 days Inhibition of human GM-CSF-induced proliferation in human HUO3 cells assessed as [3H]thymidine incorporation after 4 days by scintillation counting, IC50 = 0.324 μM. 14593182
HU03 Function assay 72 hrs Inhibition of GM-CSF-induced human HU03 cells proliferation after 72 hrs by [3H]thymidine incorporation assay, IC50 = 0.324 μM. 21105711
BAF3 Antiproliferative assay 72 hrs Antiproliferative activity against mouse BAF3 cells expressing TEL-JAK3 kinase after 72 hrs by alamar blue assay, IC50 = 0.57 μM. 19762238
T-cells Function assay 3 days Inhibition of cell proliferation of IL2-activated and CD3 and CD28 antibody-stimulated mouse CD4-positive T cells after 3 days by XTT assay, IC50 = 0.63 μM. 30460842
NK92 Function assay 20 mins Inhibition of TYK2 in human NK92 cells assessed as inhibition of IL12-induced STAT4 phosphorylation incubated for 20 mins followed by IL12 challenge for 45 mins, EC50 = 0.71 μM. 23659214
TF1 Function assay Inhibition of IL3-induced proliferation of TF1 cells, IC50 = 0.8 μM. 16934457
UT7 Function assay Inhibition of JAK2 in human UT7 cells assessed as suppression of EPO-stimulated STAT5 phosphorylation by AlphaScreen assay, INH = 1.12 μM. 26372653
Ba/F3 Function assay 60 mins Inhibition of TEL-fused TYK2 expressed in Ba/F3 cells assessed as inhibition of STAT5 phosphorylation after 60 mins by AlphaScreen assay, IC50 = 1.2 μM. 22087750
T-cells Function assay 72 hrs Inhibition of JAK3 in rat splenocytic T cells assessed as reduction in IL-2-induced cell proliferation after 72 hrs by MTS assay, IC50 = 1.2 μM. 30139575
SZ4 Function assay Inhibition of JAK3 in human SZ4 cells assessed as reduction in IL2-stimulated STAT5 phosphorylation preincubated for 1 hr followed by IL2 stimulation and measured after 15 mins by MSD assay, IC50 = 1.21 μM. 30460842
BAF3 Antiproliferative assay 72 hrs Antiproliferative activity against mouse BAF3 cells expressing TEL-JAK2 kinase after 72 hrs by alamar blue assay, IC50 = 1.574 μM. 19762238
HEL Function assay 1 hr Inhibition of JAK2 V617F mutant in human HEL cells after 1 hr, IC50 = 4.724 μM. 27771180
Jurkat Function assay 24 hrs Inhibition of anti-CD3/anti-CD28-induced IL2 production in human Jurkat cells after 24 hrs by scintillation counting, IC50 = 7.84 μM. 14593182
YT Function assay 30 ng/ml Inhibition of IL2-induced JAK3 phosphorylation in human YT cells at 30 ng/ml by immunoblotting analysis 14593182
YT Function assay 30 ng/ml Inhibition of IL2-induced STAT5A phosphorylation in human YT cells at 30 ng/ml by immunoblotting analysis 14593182
YT Function assay 30 ng/ml Inhibition of IL2-induced STAT5B phosphorylation in human YT cells at 30 ng/ml by immunoblotting analysis 14593182
NK-cells Immunosuppressive assay 1 to 5 mg/kg 4 weeks Immunosuppressive activity in naive cynomolgus monkey assessed as effect on CD3-CD16+ NK cells at 1 to 5 mg/kg, po for 4 weeks 14593182
T-cells Function assay 5 to 500 nM 1 hr Inhibition of IL2-induced Stat5 phosphorylation in human CD4+ T cells at 5 to 500 nM after 1 hr by Western blot 19053756
SUM149PT Function assay 3 uM 16 hrs Induction of PTPN6 in human SUM149PT cells assessed as inhibition of STAT3 phosphorylation at 3 uM after 16 hrs by Western blotting analysis in presence of pervanadate 24978112
Hs578T Function assay 3 uM 16 hrs Induction of PTPN6 in human Hs578T cells assessed as inhibition of STAT3 phosphorylation at 3 uM after 16 hrs by Western blotting analysis in presence of pervanadate 24978112
T-cells Function assay 50 to 300 nM 1 hr Inhibition of JAK1/JAK3 in human CD4 positive T cells assessed as inhibition of IL4-stimulated STAT6 phosphorylation at 50 to 300 nM preincubated for 1 hr followed by IL-4 stimulation measured after 30 mins by immunoblot analysis 29852068
T-cells Function assay 50 to 300 nM 1 hr Inhibition of JAK1/JAK3 in human CD4 positive T cells assessed as inhibition of IL2-stimulated STAT5 phosphorylation at Tyr-695 residue at 50 to 300 nM preincubated for 1 hr followed by IL-2 stimulation measured after 30 mins by immunoblot analysis 29852068
T-cells Function assay >300 nM 1 hr Inhibition of JAK1/JAK2/TYK2 in human CD4 positive T cells assessed as inhibition of IL6-stimulated STAT3 phosphorylation at >300 nM preincubated for 1 hr followed by IL-6 stimulation measured after 30 mins by immunoblot analysis 29852068
TALL-1 Function assay 1 uM 3 hrs Inhibition of JAK3 in human TALL-1 cells assessed as inhibition of IL-2 induced STAT5 phosphorylation at 1 uM preincubated for 3 hrs followed by IL-2 induction measured after 30 mins by immunoblotting 26258521
BA/F3 Function assay 300 nM 3 hrs Inhibition of JAK3 (unknown origin) expressed in mouse BA/F3 cells assessed as reduction of STAT5 phosphorylation at 300 nM after 3 hrs by immunoblotting analysis 26258521
OCL-AML5 Function assay 1 uM 3 hrs Inhibition of JAK2 in human OCL-AML5 cells assessed as inhibition of GM-CSF induced STAT5 phosphorylation at 1 uM preincubated for 3 hrs followed by GM-CSF induction measured after 30 mins by immunoblotting 26258521
BA/F3 Antiproliferative assay 72 hrs Antiproliferative activity against mouse BA/F3 cells expressing TEL-JAK3 after 72 hrs by cell titer glo assay 26258521
BA/F3 Function assay 1 uM 3 hrs Inhibition of JAK3 (unknown origin) expressed in mouse BA/F3 cells at 1 uM preincubated for 3 hrs followed by pulldown with streptavidin beads by immunoblotting analysis 26258521
Huh7 Function assay 10 uM 30 mins Inhibition of Tyk2 in human Huh7 cells assessed as reduction of IFNalpha5-induced STAT3 phosphorylation at 10 uM pre-incubated for 30 mins before IFNalpha5 stimulation for 30 mins mins by immunoblotting 26231159
Huh7 Function assay 10 uM 30 mins Inhibition of Tyk2 in human Huh7 cells assessed as reduction of basal level STAT3 phosphorylation at 10 uM after 30 mins by immunoblotting 26231159
Huh7 Function assay 1 uM 30 mins Inhibition of Tyk2 in human Huh7 cells assessed as reduction of IFNalpha5-induced STAT3 phosphorylation at 1 uM pre-incubated for 30 mins before IFNalpha5 stimulation for 30 mins mins by immunoblotting 26231159
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Chemische Informationen, Lagerung & Stabilität

Molekulargewicht 312.37 Formel

C16H20N6O

 Lagerung (Ab dem Eingangsdatum)
CAS-Nr. 477600-75-2 SDF herunterladen Lagerung von Stammlösungen

Synonyme CP-690550, Tasocitinib Smiles CC1CCN(CC1N(C)C2=NC=NC3=C2C=CN3)C(=O)CC#N

Löslichkeit

In vitro
Charge:

DMSO : 62 mg/mL (198.48 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
JAK3
(Cell-free assay)
1 nM
JAK2
(Cell-free assay)
20 nM
JAK1
(Cell-free assay)
112 nM
In vitro
CP-690550 ist ein spezifischer, oral verabreichter JAK3-Inhibitor, der 20- bis 100-fach weniger potent für JAK2 und JAK1 ist, mit IC50-Werten von 20 nM bzw. 112 nM. Diese Verbindung zeigt keine starke Aktivität gegen 30 andere Kinasen (alle medianen IC50 > 3000 nM). Sie hemmt die IL-2-induzierte Proliferation mit einer 30-fach höheren Potenz als ihre Wirkung auf die GM-CSF-induzierte Proliferation. Diese Chemikalie hemmt effektiv eine murine gemischte Lymphozytenreaktion (MLR) (IC50 = 91 nM). Sie hemmt potent die IL-4-induzierte Hochregulierung von CD23 (IC50=57 nM) und die Expression des Major Histocompatibility Complex Klasse II (MHCII) (IC50=71 nM) auf murinen B-Zellen. Eine aktuelle Studie zeigt, dass niedrige Dosen dieser Verbindung den Beginn der experimentellen autoimmunen Enzephalomyelitis beschleunigen, indem sie die Th17-Differenzierung potenzieren.
Kinase-Assay
JAK3 Kinase-Assay
Ein Fragment, das die katalytische Domäne der humanen JAK3 (785aa bis 1125aa, JH1 katalytische Domäne) kodiert, wird mittels PCR aus der vollständigen cDNA amplifiziert und in die EcoRI-Stelle des Baculovirus-Transfervektors pVL1393 kloniert. Rekombinantes Baculovirus wird verwendet, um Sf9-Zellen (Spodoptera frugipedra) zu infizieren, und rekombinantes GSTJAK3-Fusionsprotein wird an Glutathion-Sepharose isoliert. Das Fusionsprotein wird mit reduziertem Glutathion eluiert und in einem Puffer gelagert, der 50 mM Tris, pH 7,5, 10 mM DTT und 10 % Glycerin enthält. Die JAK3-Kinaseaktivität wird mittels ELISA wie folgt gemessen: Platten werden über Nacht mit einem zufälligen L-Glutaminsäure- und Tyrosin-Copolymer (4:1) (100 ug/mL) beschichtet. Die Platten werden gewaschen und rekombinantes JAK3 JH1:GST (100 ng/Well) mit oder ohne Inhibitoren wird bei Raumtemperatur 30 Minuten lang inkubiert, wonach HRP-konjugierter PY20 Anti-Phosphotyrosin-Antikörper (ICN) hinzugefügt und mit TMB (3,3',5,5'-Tetramethylbenzidin) entwickelt wird. Andere Kinasen (Tabelle 1) werden in E. coli oder in Insektenzellen produziert, je nachdem, was für die gegebene Kinase optimal ist. Die katalytische Aktivität von Tyrosinkinasen wird mit dem oben genannten ELISA gemessen, während Serin/Threonin-Kinasen mittels radioaktiver Enzymassays untersucht werden.
In vivo
In einem murinen Modell der heterotopen Herztransplantation (DBA2 Spenderherz in C57/BL6 Empfänger) führt Tofacitinib zu einem dosisabhängigen Anstieg der Überlebensrate transplantierter Herzen. Die EC50 (Arzneimittelkonzentration im Blut, bei der 50 % der Mäuse ihr Transplantat länger als 28 Tage behalten) beträgt ~60 ng/mL. Diese Verbindung verhindert die Abstoßung allogener Nieren bei nicht-humanen Primaten (NHPs, Macaca fascicularis) (MST von 62 und 83 Tagen für die Gruppen mit 50 bis 100 ng/ml bzw. 200 bis 400 ng/ml). Mäuse, die chronisch mit dieser Verbindung (1,5-15 mg/kg/Tag) behandelt wurden, zeigen dosis- und zeitabhängige Veränderungen der Lymphozytensubpopulationen, wenn sie mittels Durchflusszytometrie untersucht werden. Die dramatischste beobachtete Veränderung ist eine 96%ige Reduktion der NK1.1+TCRb-Zellzahlen in der Milz nach 21-tägiger Behandlung. Delayed-type Hypersensitivity (DTH)-Reaktionen bei sensibilisierten Mäusen werden nach Behandlung mit dieser Chemikalie (1,87–30 mg/kg, s.c.) dosisabhängig reduziert. Ein verlängertes Überleben neonataler Balb/c-Herzen, die in die Ohrmuschel von MHC-inkompatiblen C3H/HEN-Mäusen implantiert wurden, wird bei Monotherapie mit dieser Verbindung (10–30 mg/kg/Tag) beobachtet, aber in Kombination mit Cyclosporin (10 mg/kg/Tag) verbessert.
Literatur
  • [4] https://pubmed.ncbi.nlm.nih.gov/22252297/
  • [5] https://pubmed.ncbi.nlm.nih.gov/16378072/
  • [6] https://pubmed.ncbi.nlm.nih.gov/14678034/

Anwendungen

Methoden Biomarker Bilder PMID
Western blot JAK3 / STAT5 / p-STAT5 LMP1 / EBNA1 / BZLF1 JAK3 / p-JAK3 / STAT3
S2789-WB1
27732937
Growth inhibition assay Cell number
S2789-viability1
27732937

Klinische Studieninformationen

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

NCT-Nummer Rekrutierung Erkrankungen Sponsor/Kooperationspartner Startdatum Phasen
NCT06202560 Enrolling by invitation
Frontal Fibrosing Alopecia|Lichen Planopilaris
Institute of Dermatology Thailand
 November 29 2023 Not Applicable
NCT05487703 Completed
Arthritis Rheumatoid
Pfizer
 November 14 2022 --
NCT05082428 Completed
Ulcerative Colitis
Pfizer
 May 30 2022 --
NCT05728008 Completed
Ulcerative Colitis
IRCCS San Raffaele
 April 5 2022 --
NCT04768504 Recruiting
Immune-Mediated Colitis
Khashayar Esfahani|Sir Mortimer B. Davis - Jewish General Hospital
 March 22 2022 Phase 2

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Häufig gestellte Fragen

Frage 1:
I was just wondering what the main differences between S2789 and S5001?

Antwort:
S2789 is the base form of S5001 (Citrate). The biological activity of these two compounds are same. The S5001 (Citrate) is more suitable for oral administration.