XL019

Catalog No.S7036 Batch:S703601

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Technical Data

Formula

C25H28N6O2

Molecular Weight 444.53 CAS No. 945755-56-6
Solubility (25°C)* In vitro DMSO 16 mg/mL (35.99 mM)
Water Insoluble
Ethanol Insoluble
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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 [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]
Features Orally bioavailable JAK2-selective inhibitor and has been tested in Phase I clinical trials for treatment of Myelofibrosis.

Protocol (from 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.

Selleck's XL019 has been cited by 7 publications

A panel of janus kinase inhibitors identified with anti-inflammatory effects protect mice from lethal influenza virus infection [ Antimicrob Agents Chemother, 2024, 68(4):e0135023.] PubMed: 38470034
Xl019, a novel JAK inhibitor, suppressed osteoclasts differentiation induced by RANKL through MAPK signaling pathway [ Biochem Pharmacol, 2023, 215:115704] PubMed: 37536474
Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7] PubMed: 34997030
JAK2 Inhibition by Fedratinib Reduces Osteoblast Differentiation and Mineralisation of Human Mesenchymal Stem Cells [ Molecules, 2021, 26(3)606] PubMed: 33503825
Revisiting Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: An Improved Computational Model [ J Med Chem, 2020, 31] PubMed: 32191458
A novel human colon signet-ring cell carcinoma organoid line: establishment, characterization and application [ Carcinogenesis, 2020, 41(7):993-1004] PubMed: 31740922
P-gp Inhibition by XL019, a JAK2 Inhibitor, Increases Apoptosis of Vincristine-treated Resistant KBV20C Cells with Increased p21 and pH2AX Expression. [ Anticancer Res, 2017, 37(12):6761-6769] PubMed: 29187454

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.