solo per uso di ricerca
N. Cat.: S5001
| Target correlati | EGFR STAT Pim |
|---|---|
| Altro JAK Inibitori | BMS-986165 (Deucravacitinib) AZD1480 WP1066 Momelotinib (CYT387) Filgotinib (GLPG0634) AT9283 Gandotinib (LY2784544) Pacritinib (SB1518) NVP-BSK805 2HCl TG101209 |
| Linee cellulari | Tipo di saggio | Concentrazione | Tempo di incubazione | Formulazione | Descrizione dell'attività | PMID |
|---|---|---|---|---|---|---|
| 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 | 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 cells | 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 | 45 mins | 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 | ||
| A2780 | Function assay | Inhibition of cdk-mediated NPM phosphorylation at thr199 in human A2780 cells | 14593182 | |||
| A2780 | Function assay | Inhibition of cdk-mediated NPM phosphorylation at thr199 in human A2780 cells | 21105711 | |||
| A2780 | Function assay | Inhibition of cdk-mediated NPM phosphorylation at thr199 in human A2780 cells | 19762238 | |||
| A2780 | Function assay | Inhibition of cdk-mediated NPM phosphorylation at thr199 in human A2780 cells | 30460842 | |||
| A2780 | Function assay | Inhibition of cdk-mediated NPM phosphorylation at thr199 in human A2780 cells | 23659214 | |||
| A2780 | Function assay | Inhibition of cdk-mediated NPM phosphorylation at thr199 in human A2780 cells | 16934457 | |||
| A2780 | Function assay | Inhibition of cdk-mediated NPM phosphorylation at thr199 in human A2780 cells | 26372653 | |||
| A2780 | Function assay | Inhibition of cdk-mediated NPM phosphorylation at thr199 in human A2780 cells | 22087750 | |||
| A2780 | Function assay | Inhibition of cdk-mediated NPM phosphorylation at thr199 in human A2780 cells | 30139575 | |||
| A2780 | Function assay | Inhibition of cdk-mediated NPM phosphorylation at thr199 in human A2780 cells | 27771180 | |||
| 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 | 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 | |
| Clicca per visualizzare più dati sperimentali sulle linee cellulari | ||||||
| Peso molecolare | 504.49 | Formula | C16H20N6O.C6H8O7 |
Conservazione (Dalla data di ricezione) | |
|---|---|---|---|---|---|
| N. CAS | 540737-29-9 | Scarica SDF | Conservazione delle soluzioni stock |
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| Sinonimi | Tasocitinib Citrate,CP-690550 | Smiles | CC1CCN(CC1N(C)C2=NC=NC3=C2C=CN3)C(=O)CC#N.C(C(=O)O)C(CC(=O)O)(C(=O)O)O | ||
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In vitro |
DMSO
: 100 mg/mL
(198.21 mM)
Water : Insoluble Ethanol : Insoluble |
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In vivo |
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Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante l'esperimento)
Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non c'è una formulazione in vivo nella sezione Solubilità.)
Risultati del calcolo:
Concentrazione di lavoro: mg/ml;
Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )
Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH2O, mescolare e chiarire.
Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.
Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nell'aggiunta precedente, sia una soluzione limpida prima di procedere all'aggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno d'acqua calda possono essere utilizzati per facilitare la dissoluzione.
| Targets/IC50/Ki |
JAK3
(Cell-free assay) 1 nM
JAK2
(Cell-free assay) 20 nM
|
|---|---|
| In vitro |
Tofacitinib citrate inhibits IL-2-mediated human T cell blast proliferation and IL-15-induced CD69 expression with IC50 of 11 nM and 48 nM, respectively. Tofacitinib citrate prevents mixed lymphocyte reaction with IC50 of 87 nM. Tofacitinib citrate treatment of murine factor-dependent cell Patersen–erythropoietin receptor (FDCP-EpoR) cells harboring human wild-type or V617F JAK2 leads to prevention of cell proliferation with IC50 of 2.1 µM and 0.25 µM, respectively. Tofacitinib citrate inhibits interleukin-6-induced phosphorylation of STAT1 and STAT3 with IC50 of 23 nM and 77 nM, respectively. Moreover, Tofacitinib citrate generates a significant pro-apoptotic effect on murine FDCP-EpoR cells carrying JAK2VV617F, whereas a lesser effect is observed for cells carrying wild-type JAK2. This activity is coupled with the inhibition of phosphorylation of the key JAK2V617F-dependent downstream signaling effectors signal transducer and activator of transcription (STAT)3, STAT5, and v-akt murine thymoma viral oncogene homolog (AKT). Additionally, Tofacitinib citrate prevents IL-15-induced CD69 expression in human and cynomolgus monkey NK and CD8+ T cells in vitro.
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| Saggio chinasico |
Saggi enzimatici
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I saggi chinasici JAK1, JAK2 e JAK3 utilizzano una proteina espressa in cellule SF9 infettate da baculovirus (una proteina di fusione di GST e il dominio catalitico dell'enzima JAK umano) purificata mediante cromatografia di affinità su glutatione-Sepharose. Il substrato per la reazione è acido poliglicina-tirosina [PGT (4:1)], rivestito su piastre Nunc Maxi Sorp a 100 μg/mL durante la notte a 37 °C. Le piastre vengono lavate tre volte e l'enzima JAK viene aggiunto ai pozzetti, che contenevano 100 μL di tampone chinasico (50 mM HEPES, pH 7,3, 125 mM NaCl, 24 mM MgCl2) + ATP + 1 mM di ortovanadato di sodio. Per CP-690550 (Tofacitinib) Citrate, viene anche aggiunto per il saggio chinasico a diverse dosi. Dopo incubazione a temperatura ambiente per 30 minuti, le piastre vengono lavate tre volte. Il livello di tirosina fosforilata in un dato pozzetto viene determinato mediante saggio ELISA standard utilizzando un anticorpo anti-fosfotirosina.
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| In vivo |
Tofacitinib citrate decrease a delayed-type hyper-sensitivity response and extended cardiac allograft survival in murine models. Furthermore, Tofacitinib citrate treatment of ex-vivo-expanded erythroid progenitors from JAK2V617F-positive PV patients results in specific, antiproliferative (IC50 = 0.2 μM) and pro-apoptotic activity. In contrast, expanded progenitors from healthy controls are less sensitive to Tofacitinib citrate in proliferation (IC50 > 1.0 μM), and apoptosis assays. During 2 weeks of Tofacitinib citrate dosing at 10 and 30 mg/kg/d, a significant, time-dependent decrease in NK cell numbers relative to vehicle treatment is observed. Effector memory CD8+ cell numbers in the Tofacitinib citrate-treated group are 55% less than those observed in animals treated with vehicle.
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Riferimenti |
|
| Metodi | Biomarcatori | Immagini | PMID |
|---|---|---|---|
| Western blot | JAK3 / p-JAK3 / STAT3 LMP1 / EBNA1 / BZLF1 JAK3 / STAT5 / p-STAT5 |
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26082451 |
| Growth inhibition assay | Cell number |
|
27732937 |
(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)
| Numero NCT | Reclutamento | Condizioni | Sponsor/Collaboratori | Data di inizio | Fasi |
|---|---|---|---|---|---|
| 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 |
Domanda 1:
What is the difference between the two products (S5001, S2789)?
Risposta:
Tofacitinib (S2789) is the base form of this compound. The biological activity of these two compounds is the same. However, S5001 is better than S2789 for oral gavage.