XL019

貨號 Cat. No.: S7036
規格 Size: 5mgã€25 mg
品牌 Brand: Selleckchem

Description

XL019

Catalog No.S7036

XL019 is a potent and selective JAK2 inhibitor with IC50 of 2.2 nM, exhibiting >50-fold selectivity over JAK1, JAK3 and TYK2. Phase 1.

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5mg	USD 374	In stock	0 1 2 3 4 5 6 7 8 9 10
25mg	USD 1222	In stock	0 1 2 3 4 5 6 7 8 9 10

Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

Biological Activity

Description	XL019 is a potent and selective JAK2 inhibitor with IC50 of 2.2 nM, exhibiting >50-fold selectivity over JAK1, JAK3 and TYK2. Phase 1.
Targets	JAK2	JAK3	JAK1	TYK2
IC50	2.2 nM	214.2 nM	134.3 nM	348.3 nM ^[1]
In vitro	XL019 is a highly selective JAK2 inhibitor, binds to the active site of JAK2 displaying >50-fold selectivity against JAK1 and TYK2. XL019 reveals a desirable CYP (1A2, 2C9, 2D6, 3A4 ≥20 μM), hERG (16 μM), and P-glycoprotein inhibition (>20 μM) profile. ^[1] XL019 inhibits the activation of JAK2 as well as the mutated form JAK2V617F, which may result in the inhibition of the JAK-STAT signaling pathway and may induce apoptosis. XL019 showed more than 10-fold selective inhibition (IC50 = 64 nM) of STAT5 phosphorylation following EPO stimulation of erythroid cells compared with other cell systems. ^[2]
In vivo	XL019 significantly inhibits downstream markers pSTAT1 and pSTAT3 after administration 30, 100, and 300 mg/kg resulting in an ED50 of 42 mg/kg (pSTAT1) and 210 mg/kg (pSTAT3). XL019 has a superior pharmacodynamic profile and exhibits good oral absorption, and modest clearance and half life across species. XL019 inhibits of HEL.92.1.7 xenograft tumors growth in mice. It demonstrates 60% and 70% inhibition when dosed orally at 200 mg/kg and 300 mg/kg respectively twice a day for 14 days. Dosing at 300 mg/kg bid provided an 11.3-fold increase in apoptosis relative to vehicle control. ^[1]
Features	Orally bioavailable JAK2-selective inhibitor and has been tested in Phase I clinical trials for treatment of Myelofibrosis.

Protocol(Only for Reference)

Animal Study: ^[1]

Animal Models	HEL.92.1.7 xenograft
Dosages	100 mg/kg, 200 mg/kg, 300 mg/kg, bid
Administration	P.O.

References

Clinical Trial Information( data from http://clinicaltrials.gov)

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT00522574	Terminated	Myeloproliferative Disorders\|Myelofibrosis\|Polycythemia Vera\|Thrombocythemia, Essential	Exelixis	2007-08	Phase 1
NCT00595829	Terminated	Polycythemia Vera	Exelixis	2007-12	Phase 1

Chemical Information

Download XL019 SDF

Molecular Weight (MW)	444.53
Formula	C₂₅H₂₈N₆O₂
CAS No.	945755-56-6

Storage	3 years -20â„ƒPowder
Storage	6 months-80â„ƒin DMSO
Syonnyms	N/A

Solubility (25°C) *	In vitro	DMSO	16 mg/mL (35 mM)
		Water	<1 mg/mL (<1 mM)
		Ethanol	<1 mg/mL (<1 mM)
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.