Name: Fedratinib (TG101348)
Brand: Selleck Chemicals
SKU: S2736
Rating: 5 (102 reviews)

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.99%

99.99

Producten Vaak Samen Gebruikt Met Fedratinib (TG101348)

Momelotinib (CYT387)

This compound and Momelotinib are new JAK inhibitors being tested for managing myeloproliferative neoplasms.

Gerelateerde doelwitten	EGFR STAT Pim
Overige JAK Inhibitoren	BMS-986165 (Deucravacitinib) AZD1480 WP1066 Filgotinib (GLPG0634) AT9283 Gandotinib (LY2784544) Pacritinib (SB1518) NVP-BSK805 2HCl TG101209 Cerdulatinib (PRT062070) hydrochloride

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Concentratie	Incubatietijd	Formulering	Activiteitsbeschrijving	PMID
H1975	Apoptosis Assay	0.5-2 μM	12-48 h	DMSO	induces apoptosis in both dose- and time- dependent manner	25869210
H1650	Apoptosis Assay	0.5-2 μM	12-48 h	DMSO	induces apoptosis in both dose- and time- dependent manner	25869210
H1975	Function Assay	0.25-1 μM	24 h	DMSO	inhibits expression of apoptosis-related protein Bcl-XL, Bcl-2, survivin, XIAP	25869210
H1650	Function Assay	0.25-1 μM	24 h	DMSO	inhibits expression of apoptosis-related protein Bcl-XL, Bcl-2, survivin, XIAP	25869210
H1975	Growth Inhibition Assay	1 μM	48 h	DMSO	sensitizes cells to the cytotoxicity of erlotinib	25869210
H1650	Growth Inhibition Assay	1 μM	48 h	DMSO	sensitizes cells to the cytotoxicity of erlotinib	25869210
CD4+ T	Function Assay	0.01-1 μM	48 h	DMSO	reduces the phosphorylation levels of JAK2 and STAT3	25572535
Caco-2	Function Assay	0-120 μM	7 min		inhibits thiamine uptake with an IC50 of 2.1 µM	25063672
Caco-2	Function Assay	10/50/100 μM	2 h		decreases the flux of [3H]thiamine across the monolayer with IC50 of 6.5 μM	25063672
HEK293 MSR	Function Assay	0-10 μM	7 min		inhibits hTHTR2 with an IC50 of 1.2 µM	25063672
MedB-1	Function Assay	1/2 μM	24 h		decreases STAT6 phosphorylation concentration dependently	24977668
U2940	Function Assay	1/2 μM	24 h		decreases STAT6 phosphorylation concentration dependently	24977668
K1106	Function Assay	1/2 μM	24 h		decreases STAT6 phosphorylation concentration dependently	24977668
K562	Growth Inhibition Assay	0-1 μM	72 h		inhibits K562 cell proliferation at high concentration	24775308
MDA-MB-468	Growth Inhibition Assay	3 µM	48 h		enhanced sibcl6 induced loss of cell viability	24662818
MDA-MB-468	Growth Inhibition Assay	0-4 μM	48 h		results significant loss of viability compared to RI-BPI alone	24662818
L428	Growth Inhibition Assay	0-5 μM	48 h		inhibits cell growth significantly	24610827
KMH2	Growth Inhibition Assay	0-5 μM	48 h		inhibits cell growth significantly	24610827
L1236	Growth Inhibition Assay	0-5 μM	48 h		inhibits cell growth significantly	24610827
SUPHD1	Growth Inhibition Assay	0-5 μM	48 h		inhibits cell growth significantly	24610827
HDLM2	Growth Inhibition Assay	0-5 μM	48 h		inhibits cell growth significantly	24610827
K1106P	Growth Inhibition Assay	0-5 μM	48 h		inhibits cell growth significantly	24610827
L428	Apoptosis Assay	0/0.625/1.25 μM	48 h		induces the apoptosis	24610827
KMH2	Apoptosis Assay	0/0.625/1.25 μM	48 h		induces the apoptosis	24610827
L1236	Apoptosis Assay	0/0.625/1.25 μM	48 h		induces the apoptosis	24610827
SUPHD1	Apoptosis Assay	0/0.625/1.25 μM	48 h		induces the apoptosis	24610827
HDLM2	Apoptosis Assay	0/0.625/1.25 μM	48 h		induces the apoptosis	24610827
K1106P	Apoptosis Assay	0/0.625/1.25 μM	48 h		induces the apoptosis	24610827
L428	Function Assay	0-5 μM	24 h		inhibits JAK2/STAT signaling	24610827
KMH2	Function Assay	0-5 μM	24 h		inhibits JAK2/STAT signaling	24610827
L1236	Function Assay	0-5 μM	24 h		inhibits JAK2/STAT signaling	24610827
SUPHD1	Function Assay	0-5 μM	24 h		inhibits JAK2/STAT signaling	24610827
HDLM2	Function Assay	0-5 μM	24 h		inhibits JAK2/STAT signaling	24610827
K1106P	Function Assay	0-5 μM	24 h		inhibits JAK2/STAT signaling	24610827
MM.1S	Growth Inhibition Assay				IC50=1-3 μM	24584101
TpoR JAK2 WT	Growth Inhibition Assay				IC50=1.4 (1.3–1.5) μM	24251790
TpoR JAK2 V617F	Growth Inhibition Assay				IC50=0.8 (0.7–0.9) μM	24251790
TpoR W515L	Growth Inhibition Assay				IC50=0.8 (0.7–1.0) μM	24251790
Bcr-abl	Growth Inhibition Assay				IC50=2.7 (2.2–3.3) μM	24251790
JAK2 TW	Growth Inhibition Assay				IC50=1.8 (1.5–2.3) μM	24251790
JAK2 V617F	Growth Inhibition Assay				IC50=0.6 (0.6–0.7) μM	24251790
MedB-1	Growth Inhibition Assay	4 μM	24/48/72 h	DMSO	inhibits cell growth time dependently	23852366
K1106	Growth Inhibition Assay	4 μM	24/48/72 h	DMSO	inhibits cell growth time dependently	23852366
U2940	Growth Inhibition Assay	4 μM	24/48/72 h	DMSO	inhibits cell growth time dependently	23852366
FE-PD	Growth Inhibition Assay	0.063-4 μM			IC50=9.5 μM, inhibits cell growth dose dependently	23372669
HEL	Growth Inhibition Assay	0.063-4 μM			IC50=1.5 μM, inhibits cell growth dose dependently	23372669
K-562	Growth Inhibition Assay	0.063-4 μM			IC50=2.5 μM, inhibits cell growth dose dependently	23372669
L-82	Growth Inhibition Assay	0.063-4 μM			IC50=0.98 μM, inhibits cell growth dose dependently	23372669
MAC-1	Growth Inhibition Assay	0.063-4 μM			IC50=0.52 μM, inhibits cell growth dose dependently	23372669
MAC-2A	Growth Inhibition Assay	0.063-4 μM			IC50=0.69 μM, inhibits cell growth dose dependently	23372669
MAC-2B	Growth Inhibition Assay	0.063-4 μM			IC50=0.54 μM, inhibits cell growth dose dependently	23372669
MY-LA	Growth Inhibition Assay	0.063-4 μM			IC50=2.1 μM, inhibits cell growth dose dependently	23372669
NC-NC	Growth Inhibition Assay	0.063-4 μM			IC50=1.0 μM, inhibits cell growth dose dependently	23372669
SE-AX	Growth Inhibition Assay	0.063-4 μM			IC50=1.5 μM, inhibits cell growth dose dependently	23372669
SR-786	Growth Inhibition Assay	0.063-4 μM			IC50=4.6 μM, inhibits cell growth dose dependently	23372669
M-MOK	Growth Inhibition Assay	25 µM	24/48/72 h	DMSO	inhibits cell growth time dependently	21853157
HEL	Growth Inhibition Assay				IC50=305 nM	18394554
Ba/F3 JAK2V617F	Growth Inhibition Assay				IC50=270 nM	18394554
MV4-11	Antiproliferative assay		72 hrs		Antiproliferative activity against human MV4-11 cells after 72 hrs by celltiter-blue assay, EC50 = 0.079 μM.	28280261
MM1S	Antiproliferative assay		72 hrs		Antiproliferative activity against human MM1S cells after 72 hrs by trypan blue exclusion assay, IC50 = 1 μM.	28280261
NB1643	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 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
Klik om meer experimentele gegevens over de cellijn te bekijken

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Moleculair gewicht	524.68	Formule	C₂₇H₃₆N₆O₃S	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	936091-26-8	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	SAR302503			Smiles	CC1=CN=C(N=C1NC2=CC(=CC=C2)S(=O)(=O)NC(C)(C)C)NC3=CC=C(C=C3)OCCN4CCCC4

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 100 mg/mL (190.59 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Moleculair gewicht
=	×	×

Verdunningscalculator Moleculair gewicht calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	4.000mg/ml (7.62mM)	Taking the 1 mL working solution as an example, add 50 μL of 80 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formuleringscalculator (Heldere oplossing)

Stap 1: Voer de onderstaande informatie in (Aanbevolen: Een extra dier voor het geval van verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in het gedeelte Oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-mastervloeistof: mg geneesmiddel vooraf opgelost in μL DMSO ( Concentratie mastervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de partij geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toeμL PEG300, mengen en helder maken, voeg vervolgens toeμL Tween 80, mengen en helder maken, voeg vervolgens toe μL ddH₂O, mengen en helder maken.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toe μL Maïsolie, mengen en helder maken.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysische methoden zoals vortexen, echografie of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Targets/IC₅₀/Ki	JAK2 (Cell-free assay) 3 nM JAK2 (V617F) (Cell-free assay) 3 nM FLT3 (Cell-free assay) 15 nM RET (Cell-free assay) 48 nM
In vitro	Fedratinib (TG101348) significantly inhibits JAK2 V617F, Flt3, and Ret with IC50 of 3 nM, 15 nM, and 48 nM, respectively. This compound has an IC50 ~300-fold higher for the closely related JAK3 and is a less potent inhibitor of the JAK1 and TYK2 family members. It inhibits proliferation of a human erythroblast leukemia (HEL) cell line that harbors the JAK2V617F mutation, as well as a murine pro-B cell line expressing human JAK2V617F (Ba/F3 JAK2V617F), with IC50 of 305 nM and 270 nM, respectively. TG-101348 also inhibits proliferation of parental Ba/F3 cells to a comparable level, with IC50 of ~420 nM. Its treatment reduces STAT5 phosphorylation at concentrations that parallel the concentrations required to inhibit cell proliferation. TG101348 induces apoptosis in both HEL and Ba/F3 JAK2V617F cells in a dose-dependent manner. It does not show proapoptotic activity in control normal human dermal fibroblasts at concentrations up to 10 μM, and the antiproliferative IC50 against fibroblasts is >5 μM. This compound treatment decreases GATA-1 expression, which is associated with erythroid-skewing of JAK2V617F⁺ progenitor differentiation, and inhibits STAT5 as well as GATA S310 phosphorylation. TG101348 inhibits the proliferation of HMC-1.1 (KITV560G) cells, with somewhat lower potency than HMC-1.2 (KITD816V, KITV560G) cells, with IC50 of 740 nM and 407 nM, respectively.
Kinase Assay	Celvrije Kinase Activiteit Assays
Kinase Assay	Fedratinib (TG101348) IC50-waarden worden commercieel bepaald met behulp van de InVitrogen kinase profiling service voor een 223 kinase screening die JAK2 en JAK2V617F omvatte, of Carna Biosciences voor de screening van alle Janus kinase-familieleden, inclusief JAK1 en Tyk2. De ATP-concentratie wordt ingesteld op ongeveer de Km-waarde voor elke kinase.
In vivo	Fedratinib (TG101348) has potential for efficacious treatment of JAK2V617F-associated myeloproliferative diseases (MPD). In treated animals, there is a statistically significant reduction in hematocrit and leukocyte count, a dose-dependent reduction/elimination of extramedullary hematopoiesis, and, at least in some instances, evidence for attenuation of myelofibrosis, correlated with surrogate endpoints, including reduction/elimination of JAK2V617F disease burden, suppression of endogenous erythroid colony formation, and in vivo inhibition of JAK-STAT signal transduction. There are no apparent toxicities and no effect on T cell number. Oral administration of this compound (120 mg/kg) significantly inhibits PV progenitor erythroid differentiation in vivo.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/18394554/ [2] https://pubmed.ncbi.nlm.nih.gov/18394555/ [3] https://pubmed.ncbi.nlm.nih.gov/20485374/

Toepassingen (Applications)

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	p-JAK2 / p-STAT1 / p-STAT3 / p-STAT6 / p-STAT5 / JAK2 c-Myc / PIM1		24610827
Growth inhibition assay	Cell proliferation		24610827

Informatie klinische proef (Clinical Trial Information)

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Rekrutering	Aandoeningen	Sponsor/Medewerkers	Startdatum	Fasen
NCT04955938	Recruiting	IDH Mutation\|IDH1 Mutation\|IDH2 Gene Mutation\|Blood Cancer\|Myeloproliferative Neoplasm	University of Chicago	October 29 2021	Phase 1
NCT05051553	Completed	Healthy Volunteers	Bristol-Myers Squibb	September 21 2021	Phase 1
NCT04702464	Completed	Healthy Volunteers	Celgene\|Impact Biomedicines Inc. a wholly owned subsidiary of Celgene Corporation	January 12 2021	Phase 1
NCT03983161	Completed	Healthy Volunteers\|Hepatic Impairment	Celgene\|Impact Biomedicines Inc. a wholly owned subsidiary of Celgene Corporation	September 4 2019	Phase 1
NCT03983239	Completed	Healthy Volunteers	Celgene\|Impact Biomedicines Inc. a wholly owned subsidiary of Celgene Corporation	June 21 2019	Phase 1

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Fedratinib (TG101348) JAK2-remmer

Moleculair gewicht: 524.68

Kwaliteitscontrole (Quality Control)

Producten Vaak Samen Gebruikt Met Fedratinib (TG101348)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie klinische proef (Clinical Trial Information)

Fedratinib (TG101348) JAK2-remmer

Moleculair gewicht: 524.68

Kwaliteitscontrole (Quality Control)

Producten Vaak Samen Gebruikt Met Fedratinib (TG101348)

Celkweek, behandeling & werkconcentratie (Cell Culture, Treatment & Working Concentration)

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie klinische proef (Clinical Trial Information)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)