Pyrrolidine-2-carboxylic acid {4-[2-(4-morpholin-4-yl-phenylamino)-pyrimidin-4-yl]-phenyl}-amide
XL019
CAS: 945755-56-6
Molecular Formula: C25H28N6O2
Pyrrolidine-2-carboxylic acid {4-[2-(4-morpholin-4-yl-phenylamino)-pyrimidin-4-yl]-phenyl}-amide - Names and Identifiers
Pyrrolidine-2-carboxylic acid {4-[2-(4-morpholin-4-yl-phenylamino)-pyrimidin-4-yl]-phenyl}-amide - Physico-chemical Properties
| Molecular Formula | C25H28N6O2 |
| Molar Mass | 444.53 |
| Solubility | Soluble in DMSO, not in water |
| Storage Condition | -20℃ |
| Use | XL019 is an effective, orally active and selective JAK2 inhibitor. The IC50 for JAK2,JAK1 and JAK3 is 2.2, 134.3 and 214.2 nM respectively. The selectivity of XL019 for JAK2 is 50 times or higher than that of more 100 serine/threonine and tyrosine kinases (including other members of the JAK family). Inhibitory effect of XL019 on STAT3 and STAT5 phosphorylation in JAK2 V617F and wild-type JAK2 cells. |
| In vitro study | XL019 is a highly selective inhibitor of JAK2, binding to the active site of JAK2 with 50-fold selectivity over JAK1 and tyk2. XL019 exhibited ideal inhibition of CYP(1A2,2C9,2D6,3A4> 20 μm),hERG(16 μm), and P-glycoprotein (> 20 μm). XL019 inhibits activation of JAK2 as well as the mutant form of JAK2V617F, which may lead to JAK-STAT inhibition of the signaling pathway and may induce apoptosis. XL019 showed more than 10-fold selective inhibition in erythroid cells compared to other cellular systems (IC 50=64 nM). XL019 is a highly selective inhibitor of JAK2, binding to the active site of JAK2 with 50-fold selectivity over JAK1 and tyk2. XL019 exhibited ideal inhibition of CYP(1A2,2C9,2D6,3A4> 20 μm),hERG(16 μm), and P-glycoprotein (> 20 μm). XL019 inhibits activation of JAK2 as well as the mutant form of JAK2V617F, which may lead to JAK-STAT inhibition of the signaling pathway and may induce apoptosis. XL019 showed more than 10-fold selective inhibition in erythroid cells compared to other cellular systems (IC 50=64 nM). |
| In vivo study | After administration of 30,100, and 300 mg/kg, XL019 significantly inhibited the downstream markers pSTAT1 and pSTAT3, resulting in an ED 50 of 42 mg/kg, respectively (pSTAT1). And 210 mg/kg (pSTAT3). XL019 has superior efficacy and good oral absorption, and shows moderate clearance and half-life in different species. In mice, XL019 inhibited HEL.92.1.7 xenograft tumor growth with 200 mg / kg and 300 mg / kg administered twice daily for up to 14 days showing 60% and 70% inhibition, respectively. The 300 mg/kg dose exhibited a 11.3-fold increase in apoptosis compared to the control. after administration of 30,100, and 300 mg/kg, XL019 significantly inhibited the downstream markers pSTAT1 and pSTAT3, resulting in an ED 50 of 42 mg/kg (pSTAT1), respectively. And 210 mg/kg (pSTAT3). XL019 has superior efficacy and good oral absorption, and shows moderate clearance and half-life in different species. In mice, XL019 inhibited HEL.92.1.7 xenograft tumor growth with 200 mg / kg and 300 mg / kg administered twice daily for up to 14 days showing 60% and 70% inhibition, respectively. The 300 mg/kg dose exhibited a 11.3-fold increase in apoptosis compared to the control. |
Pyrrolidine-2-carboxylic acid {4-[2-(4-morpholin-4-yl-phenylamino)-pyrimidin-4-yl]-phenyl}-amide - Reference
| Reference Show more | 1: Verstovsek S, Tam CS, Wadleigh M, Sokol L, Smith CC, Bui LA, Song C, Clary DO, Olszynski P, Cortes J, Kantarjian H, Shah NP. Phase I evaluation of XL019, an oral, potent, and selective JAK2 inhibitor. Leuk Res. 2013 Dec 11. pii: S0145-2126(13)00425-6. doi: 10.1016/j.leukres.2013.12.006. [Epub ahead of print。 |
Pyrrolidine-2-carboxylic acid {4-[2-(4-morpholin-4-yl-phenylamino)-pyrimidin-4-yl]-phenyl}-amide - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.25 ml | 11.248 ml | 22.496 ml |
| 5 mM | 0.45 ml | 2.25 ml | 4.499 ml |
| 10 mM | 0.225 ml | 1.125 ml | 2.25 ml |
| 5 mM | 0.045 ml | 0.225 ml | 0.45 ml |
Last Update：2024-01-02 23:10:35
Pyrrolidine-2-carboxylic acid {4-[2-(4-morpholin-4-yl-phenylamino)-pyrimidin-4-yl]-phenyl}-amide - Reference Information
| biological activity | XL019 is an effective and selective JAK2 inhibitor with IC50 of 2.2 nM, which acts on JAK1, JAK3 and TYK2. The selectivity is 50 times higher. Phase 1. XL019 is an effective and selective JAK2 inhibitor, IC50 is 2.2 nM, which acts on JAK1, JAK3 and TYK2. The selectivity is 50 times higher. Phase 1. |
| in vitro study | XL019 is a highly selective JAK2 inhibitor, which binds to the active site of JAK2 and is 50 times more selective than JAK1 and TYK2. XL019 showed ideal inhibition of CYP(1A2,2C9,2D6,3A4 ≥ 20 μM),hERG(16 μM), and P-glycoprotein (> 20 μM). XL019 inhibits the activation of JAK2 and JAK2V617F of mutant forms, which may lead to the inhibition of JAK-STAT signal transduction pathways and can induce apoptosis. Compared with other cell systems, XL019 showed more than 10-fold selective inhibition in erythroid cells (IC 50=64 nM). XL019 is a highly selective inhibitor of JAK2, which binds to the active site of JAK2, and the selectivity is 50 times that of JAK1 and TYK2. XL019 showed ideal inhibition of CYP(1A2,2C9,2D6,3A4 ≥ 20 μM),hERG(16 μM), and P-glycoprotein (> 20 μM). XL019 inhibits the activation of JAK2 and JAK2V617F of mutant forms, which may lead to the inhibition of JAK-STAT signal transduction pathways and can induce apoptosis. Compared with other cell systems, XL019 showed more than 10-fold selective inhibition in erythroid cells (IC 50=64 nM). |
| in vivo study | after administration of 30,100, and 300 mg/kg, XL019 significantly inhibited the downstream markers pSTAT1 and pSTAT3, resulting in ED 50 of 42 mg/kg (pSTAT1) and 210 mg/kg (pSTAT3), respectively. XL019 has superior efficacy and good oral absorption, showing moderate clearance and half-life in different species. In mice, XL019 inhibits HEL. 92.1.7 xenograft tumor growth, 200 mg/kg and 300 mg/kg were administered twice daily until 14 days, showing 60% and 70% inhibition. Compared with the control, the dose of 300 mg/kg showed a 11.3-fold increase in apoptosis. after administration of 30,100, and 300 mg/kg, XL019 significantly inhibited the downstream markers pSTAT1 and pSTAT3, resulting in ED 50 of 42 mg/kg (pSTAT1) and 210 mg/kg (pSTAT3), respectively. XL019 has superior efficacy and good oral absorption, showing moderate clearance and half-life in different species. In mice, XL019 inhibits HEL. 92.1.7 xenograft tumor growth, 200 mg/kg and 300 mg/kg were administered twice daily until 14 days, showing 60% and 70% inhibition. Compared with the control, the dose of 300 mg/kg showed a 11.3-fold increase in apoptosis. |
| features | Orally bioavailable JAK2-selective inhibitor and has been testing in Phase I clinical trials for treatment of Myelofibrosis. |
| target | TargetValue JAK2 (Cell-free assay) 2.2 nM PDGFRβ (Cell-free assay) 125.4 nM JAK1 (Cell-free assay) 134.3 nM FLT3 (Cell-free assay) 139.7 nM JAK3 (Cell-free assay) 214.2 nM |
| Target | Value |
| JAK2 (Cell-free assay) | 2.2 nM |
| PDGFRβ (Cell-free assay) | 125.4 nM |
| JAK1 (Cell-free assay) | 134.3 nM |
| FLT3 (Cell-free assay) | 139.7 nM |
| JAK3 (Cell-free assay) | 214.2 nM |
Last Update：2024-04-09 21:04:16
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Spot supply
Product Name: XL019 Visit Supplier Webpage Request for quotationCAS: 945755-56-6
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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