XL019
Modify Date: 2024-01-14 12:26:56
XL019 structure
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Common Name | XL019 | ||
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| CAS Number | 945755-56-6 | Molecular Weight | 444.529 | |
| Density | 1.3±0.1 g/cm3 | Boiling Point | N/A | |
| Molecular Formula | C25H28N6O2 | Melting Point | N/A | |
| MSDS | N/A | Flash Point | N/A | |
Use of XL019XL019 is a potent and selective JAK2 inhibitor with IC50 of 2.2 nM, 100 fold selectivity over JAK1; shows good biochemical and cellular potency against JAK2 with good selectivity against the Janus Kinase family as well as a broad kinase panel.IC50 Value: 2.2 nM (JAK2); 214.2 nM (JAK3) [1]XL019 was selected as a clinical candidate and advanced into human clinical trials where it was evaluated in patients with primary myelofibrosis, post-polycythemia vera, or post-essential thrombocythemia myelofibrosis.in vitro: Analogue XL019 was also evaluated against a selectivity panel of 118 kinases. Targets for which XL019 exhibited IC50 <1000 nM are displayed. Overall XL019 is a highly selective JAK2 inhibitor displaying >50-fold selectivity against all kinases tested including JAK family members JAK1 and TYK2. Further in vitro evaluation of XL019 revealed that it demonstrated a desirable CYP (1A2, 2C9, 2D6, 3A4 20 μM), hERG (16 μM), and P-glycoprotein inhibition (>20 μM) profile [1].in vivo: XL019 was administered orally to mice bearing HEL92.1.7 tumors and inhibition of STAT phosphorylation was measured after 4 h. A significant inhibition of downstream markers pSTAT1 and pSTAT3 is observed at 30, 100, and 300 mg/kg resulting in an ED50 of 42 mg/kg (pSTAT1) and 210 mg/kg (pSTAT3). 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. Harvested tumors were also subjected to immunohistochemical analysis of microvessel density (CD31), proliferation (Ki67) and apoptosis (TUNEL). Dosing at 300 mg/kg bid provided an 11.3-fold increase in apoptosis relative to vehicle control [1]. |
| Name | (S)-N-(4-(2-((4-morpholinophenyl)amino)pyrimidin-4-yl)phenyl)pyrrolidine-2-carboxamide |
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| Synonym | More Synonyms |
| Description | XL019 is a potent and selective JAK2 inhibitor with IC50 of 2.2 nM, 100 fold selectivity over JAK1; shows good biochemical and cellular potency against JAK2 with good selectivity against the Janus Kinase family as well as a broad kinase panel.IC50 Value: 2.2 nM (JAK2); 214.2 nM (JAK3) [1]XL019 was selected as a clinical candidate and advanced into human clinical trials where it was evaluated in patients with primary myelofibrosis, post-polycythemia vera, or post-essential thrombocythemia myelofibrosis.in vitro: Analogue XL019 was also evaluated against a selectivity panel of 118 kinases. Targets for which XL019 exhibited IC50 <1000 nM are displayed. Overall XL019 is a highly selective JAK2 inhibitor displaying >50-fold selectivity against all kinases tested including JAK family members JAK1 and TYK2. Further in vitro evaluation of XL019 revealed that it demonstrated a desirable CYP (1A2, 2C9, 2D6, 3A4 20 μM), hERG (16 μM), and P-glycoprotein inhibition (>20 μM) profile [1].in vivo: XL019 was administered orally to mice bearing HEL92.1.7 tumors and inhibition of STAT phosphorylation was measured after 4 h. A significant inhibition of downstream markers pSTAT1 and pSTAT3 is observed at 30, 100, and 300 mg/kg resulting in an ED50 of 42 mg/kg (pSTAT1) and 210 mg/kg (pSTAT3). 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. Harvested tumors were also subjected to immunohistochemical analysis of microvessel density (CD31), proliferation (Ki67) and apoptosis (TUNEL). Dosing at 300 mg/kg bid provided an 11.3-fold increase in apoptosis relative to vehicle control [1]. |
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| Related Catalog | |
| Target |
JAK2:2.2 nM (IC50) JAK3:214.2 nM (IC50) |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Molecular Formula | C25H28N6O2 |
| Molecular Weight | 444.529 |
| Exact Mass | 444.227386 |
| PSA | 91.41000 |
| LogP | 1.71 |
| Appearance of Characters | light yellow solid |
| Index of Refraction | 1.662 |
| Storage condition | -20℃ |
| s7036 |
| 2-Pyrrolidinecarboxamide, N-[4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]phenyl]-, (2S)- |
| N-[4-(2-{[4-(4-Morpholinyl)phenyl]amino}-4-pyrimidinyl)phenyl]-L-prolinamide |
| xl019 |