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XL019 JAK inhibitor

Cat.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.

Chemical Structure

Molecular Weight: 444.53

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: S703601 DMSO]16 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 99.01%

99.01

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Chemical Information, Storage & Stability

Molecular Weight	444.53	Formula	C₂₅H₂₈N₆O₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	945755-56-6	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	C1CC(NC1)C(=O)NC2=CC=C(C=C2)C3=NC(=NC=C3)NC4=CC=C(C=C4)N5CCOCC5

Solubility

In vitro
Batch:

DMSO : 16 mg/mL ( (35.99 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight 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 Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.400mg/ml (0.90mM)	Taking the 1 mL working solution as an example, add 50 μL of 8 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.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.400mg/ml (0.90mM)	Taking the 1 mL working solution as an example, add 50 μL of 8 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Features	Orally bioavailable JAK2-selective inhibitor and has been tested in Phase I clinical trials for treatment of Myelofibrosis.
Targets/IC₅₀/Ki	JAK2 ^[1] (Cell-free assay) 2.2 nM PDGFRβ ^[1] (Cell-free assay) 125.4 nM JAK1 ^[1] (Cell-free assay) 134.3 nM FLT3 ^[1] (Cell-free assay) 139.7 nM JAK3 ^[1] (Cell-free assay) 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. This compound reveals a desirable CYP (1A2, 2C9, 2D6, 3A4 ≥20 μM), hERG (16 μM), and P-glycoprotein inhibition (>20 μM) profile. ^[1] It 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. This chemical 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). This compound has a superior pharmacodynamic profile and exhibits good oral absorption, and modest clearance and half life across species. It 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]
References	https://pubmed.ncbi.nlm.nih.gov/23127890/ https://pubmed.ncbi.nlm.nih.gov/20008249/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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