产品名称

英文名称：XL019

同义词

XL019、945755-56-6、(S)-N-(4-(2-((4-morpholinophenyl)amino)pyrimidin-4-yl)phenyl)pyrrolidine-2-carboxamide、XL-019、4L1AM42NVA、(2S)-N-[4-[2-[[4-(4-Morpholinyl)phenyl]amino]-4-pyrimidinyl]phenyl]-2-pyrrolidinecarboxamide、(2S)-N-[4-(2-{[4-(MORPHOLIN-4-YL)PHENYL

产品性质

CAS编号：945755-56-6

分子式：C25H28N6O2

分子量：444.53

PubChem编号：57990869

英文别名：XL019|945755-56-6|(S)-N-(4-(2-((4-morpholinophenyl)amino)pyrimidin-4-yl)phenyl)pyrrolidine-2-carboxamide|XL-019|4L1AM42NVA|(2S)-N-[4-[2-[[4-(4-Morpholinyl)phenyl]amino]-4-pyrimidinyl]phenyl]-2-pyrrolidinecarboxamide|(2S)-N-[4-(2-{[4-(MORPHOLIN-4-YL)PHENYL

规格或纯度：98%

英文名称：XL019

生化机理：DescriptionIC50 Value 2.2 nM (JAK2); 214.2 nM (JAK3) [1]XL019 is a potent and selective JAK2 inhibitor. XL019 shows good biochemical and cellular potency against JAK2 with good selectivity against the Janus Kinase family as well as a broad kinase panel. 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].Toxicity N/AClinical trial A Safety Study of XL-019 in Adults With Myelofibrosis. Phase 1

储存温度：-20°C储存

运输条件：超低温冰袋运输

产品介绍：产品介绍XL019 是一种有效的、口服活性的、选择性的 JAK2 抑制剂，对 JAK2，JAK1，JAK3 的 IC50 分别为 2.2、134.3、214.2 nM。XL019 对JAK2的选择性是 100 多种丝氨酸/苏氨酸和酪氨酸激酶（包括 JAK 家族的其他成员）的 50 倍或更高。XL019 对 JAK2 V617F 和野生型 JAK2 细胞中 STAT3 和 STAT5 磷酸化的抑制作用。

IUPAC Name：(2S)-N-[4-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]phenyl]pyrrolidine-2-carboxamide

INCHI：InChI=1S/C25H28N6O2/c32-24(23-2-1-12-26-23)28-19-5-3-18(4-6-19)22-11-13-27-25(30-22)29-20-7-9-21(10-8-20)31-14-16-33-17-15-31/h3-11,13,23,26H,1-2,12,14-17H2,(H,28,32)(H,27,29,30)/t23-/m0/s1

InChi Key：ISOCDPQFIXDIMS-QHCPKHFHSA-N

Canonical SMILES：C1CC(NC1)C(=O)NC2=CC=C(C=C2)C3=NC(=NC=C3)NC4=CC=C(C=C4)N5CCOCC5

Isomeric SMILES：C1C[C@H](NC1)C(=O)NC2=CC=C(C=C2)C3=NC(=NC=C3)NC4=CC=C(C=C4)N5CCOCC5

PubChem CID：57990869

CAS Registry No.：945755-56-6

溶解性：DMSO 16 mg/mL Water <1 mg/mL Ethanol <1 mg/mL

产品包装