XL019

Catalog No.S7036

For research use only.

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.

XL019 Chemical Structure

CAS No. 945755-56-6

Selleck's XL019 has been cited by 5 Publications

Purity & Quality Control

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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.
Features Orally bioavailable JAK2-selective inhibitor and has been tested in Phase I clinical trials for treatment of Myelofibrosis.
Targets
JAK2 [1]
(Cell-free assay)
PDGFRβ [1]
(Cell-free assay)
JAK1 [1]
(Cell-free assay)
FLT3 [1]
(Cell-free assay)
JAK3 [1]
(Cell-free assay)
2.2 nM 125.4 nM 134.3 nM 139.7 nM 214.2 nM
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]

Protocol (from reference)

Animal Research:[1]
  • Animal Models: HEL.92.1.7 xenograft
  • Dosages: 100 mg/kg, 200 mg/kg, 300 mg/kg, bid
  • Administration: P.O.

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 444.53
Formula

C25H28N6O2

CAS No. 945755-56-6
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1CC(NC1)C(=O)NC2=CC=C(C=C2)C3=NC(=NC=C3)NC4=CC=C(C=C4)N5CCOCC5

In vivo Formulation Calculator (Clear solution)

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Molarity Calculator

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00595829 Terminated Drug: XL019 Polycythemia Vera Exelixis December 2007 Phase 1
NCT00522574 Terminated Drug: XL019 Myeloproliferative Disorders|Myelofibrosis|Polycythemia Vera|Thrombocythemia Essential Exelixis August 2007 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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