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

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Controllo Qualità (Quality Control)

Lotto: Purezza: 99.99%

99.99

Prodotti spesso usati con Fedratinib (TG101348)

Momelotinib (CYT387)

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

Target correlati	EGFR STAT Pim
Altro JAK Inibitori	BMS-986165 (Deucravacitinib) AZD1480 WP1066 Filgotinib (GLPG0634) AT9283 Gandotinib (LY2784544) Pacritinib (SB1518) NVP-BSK805 2HCl TG101209 Cerdulatinib (PRT062070) hydrochloride

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Linee cellulari	Tipo di saggio	Concentrazione	Tempo di incubazione	Formulazione	Descrizione dell'attività	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
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Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Peso molecolare	524.68	Formula	C₂₇H₃₆N₆O₃S	Conservazione (Dalla data di ricezione)	3 anni-20°Cpolvere
N. CAS	936091-26-8	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente
Sinonimi	SAR302503			Smiles	CC1=CN=C(N=C1NC2=CC(=CC=C2)S(=O)(=O)NC(C)(C)C)NC3=CC=C(C=C3)OCCN4CCCC4

Solubilità (Solubility)

In vitro
Lotto:

DMSO : 100 mg/mL (190.59 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Water : Insoluble

Ethanol : Insoluble

Calcolatore di Molarità

Massa	Concentrazione	Volume	Peso molecolare
=	×	×

Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo Lotto:
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 Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	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.

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante l'esperimento)

Dosaggio: mg/kg Peso medio degli animali: g Volume di dosaggio per animale:μL Numero di animali:

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.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

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.

Meccanismo d'azione (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.
Saggio chinasico	Saggi di attività chinasica senza cellule
Saggio chinasico	I valori di IC50 di Fedratinib (TG101348) sono determinati commercialmente utilizzando il servizio di profilazione delle chinasi InVitrogen per uno screening di 223 chinasi che includeva JAK2 e JAK2V617F o Carna Biosciences per lo screening di tutti i membri della famiglia Janus chinasi, inclusi JAK1 e Tyk2. La concentrazione di ATP è impostata approssimativamente al valore Km per ciascuna chinasi.
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.
Riferimenti	[1] https://pubmed.ncbi.nlm.nih.gov/18394554/ [2] https://pubmed.ncbi.nlm.nih.gov/18394555/ [3] https://pubmed.ncbi.nlm.nih.gov/20485374/

Applicazioni (Applications)

Metodi	Biomarcatori	Immagini	PMID
Western blot	p-JAK2 / p-STAT1 / p-STAT3 / p-STAT6 / p-STAT5 / JAK2 c-Myc / PIM1		24610827
Growth inhibition assay	Cell proliferation		24610827

Informazioni sullo studio clinico (Clinical Trial Information)

(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)

Numero NCT	Reclutamento	Condizioni	Sponsor/Collaboratori	Data di inizio	Fasi
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

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Fedratinib (TG101348) JAK2 Inhibitor

Struttura chimica

Peso molecolare: 524.68

Controllo Qualità (Quality Control)

Prodotti spesso usati con Fedratinib (TG101348)

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Solubilità (Solubility)

Calcolatore di Molarità

Calcolatore di formulazione in vivo (Soluzione chiara)

Meccanismo d'azione (Mechanism of Action)

Applicazioni (Applications)

Informazioni sullo studio clinico (Clinical Trial Information)

Fedratinib (TG101348) JAK2 Inhibitor

Struttura chimica

Peso molecolare: 524.68

Controllo Qualità (Quality Control)

Prodotti spesso usati con Fedratinib (TG101348)

Coltura cellulare, trattamento e concentrazione di lavoro (Cell Culture, Treatment & Working Concentration)

Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Solubilità (Solubility)

Calcolatore di Molarità

Calcolatore di formulazione in vivo (Soluzione chiara)

Meccanismo d'azione (Mechanism of Action)

Applicazioni (Applications)

Informazioni sullo studio clinico (Clinical Trial Information)

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)