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XL019JAK2 inhibitor,potent and selective

XL019

Catalog No. A3937
Size Price Stock Qty
10mM (in 1mL DMSO) $99.00 In stock
5mg $90.00 In stock
10mg $150.00 In stock
50mg $450.00 In stock
100mg $750.00 In stock

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Sample solution is provided at 25 µL, 10mM.

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Chemical structure

XL019

Biological Activity

Description XL019 is a potent and selective inhibitor of JAK2 with IC50 value of 2.2 nM.
Targets JAK2          
IC50 2.2 nM          

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Chemical Properties

Cas No. 945755-56-6 SDF Download SDF
Synonyms XL-019;XL 019
Chemical Name (2S)-N-[4-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]phenyl]pyrrolidine-2-carboxamide
Canonical SMILES C1CC(NC1)C(=O)NC2=CC=C(C=C2)C3=NC(=NC=C3)NC4=CC=C(C=C4)N5CCOCC5
Formula C25H28N6O2 M.Wt 444.53
Solubility >11.1mg/mL in DMSO Storage Store at -20°C
General tips N/A
Shipping Condition N/A

Background

XL019 is a potent and selective inhibitor of JAK2 with IC50 value of 2.2 nM.
JAK kinases were first identified in 1989 and characterized by the presence of two tyrosine kinase domains. There are four members in the JAK family, which are JAK1, JAK2, JAK3 and TYK2. JAK2 played an important role in the pathways that control erythroid, myeloid and megakaryocytic development. JAK2 mediates signaling through erythropoietin receptor, thrombopoietin receptor and cytokine receptor that harbor the common β-chain (e.g. IL3 receptor) and IFN-γ receptors [38]. JAK2 inhibitors are a novel class of agents with promising results for treating patients with polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF) [1]. XL019 was selected as a clinical candidate and advanced into human clinical trials where it was evaluated in patients with PMF, post-PV, or post-ET MF [2].
XL019 shows good biochemical and cellular potency against JAK2 with good selectivity, against a panel of over 100 serine/threonine and tyrosine kinases, including other members of the JAK family [2]. Analogue XL019 was evaluated against a select panel of 118 kinases. Targets for which XL019 exhibited IC50 <1000 nM are displayed. XL019 is a highly selective JAK2 inhibitor displaying >50-fold selectivity against all kinases tested including JAK1 and TYK2. XL019 was a desirable CYP, hERG (16 μM), and P-glycoprotein inhibition (>20 μM).
XL019 had a superior pharmacodynamic profile and thus was evaluated in an efficacy experiment measuring growth inhibition of HEL.92.1.7 xenograft tumors in mice. Derivative XL019 demonstrated 60% and 70% inhibition when dosed orally at 200 mg/kg and 300 mg/kg respectively twice a day for 14 days. Thirty patients received XL019 for a median of 91 days. All of them have discontinued XL019 therapy. Toxicity: N/A Clinical trial: A Safety Study of XL-019 in Adults With Myelofibrosis [2].
References:
[1]. Fabio P.S. Santos, Srdan Verstovsek. JAK2 inhibitors: What's the true therapeutic potential?. Blood Reviews, 2011, 25: 53-63.
[2]. Srdan Verstovsek, Constantine S. Tam, Martha Wadleigh, et al. Phase I evaluation of XL019, an oral, potent, and selective JAK2 inhibitor. Leukemia Research, 2014, 38: 316-322.