基本描述

英文别名	Pacritinib (SB1518) \| (16E)-11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,27-triazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(24),2(27),3,5,8(26),9,11,16,21(25),22-decaene \| Oral JAK2 Inhibitor SB1518 \| SCHEMBL22819303 \| AKOS037515687 \| DB11697 \| NCGC0038156
规格或纯度	Moligand™, ≥95%
英文名称	Pacritinib (SB1518)
生化机理	帕克替尼（SB1518）是 Janus 激酶 2 (JAK2) 和 Fms-Like 酪氨酸激酶 3 (FLT3) 的强效选择性抑制剂，在无细胞实验中的 IC50 值分别为 23 和 22 nM。第 3 阶段
储存温度	-20°C储存
运输条件	超低温冰袋运输
作用类型	抑制剂
作用机制	酪氨酸蛋白激酶受体 FLT3 抑制剂
产品介绍	Information Pacritinib (SB1518) is a potent and selective inhibitor ofJanus Kinase 2 (JAK2)andFms-Like Tyrosine Kinase-3 (FLT3)withIC50sof 23 and 22 nM in cell-free assays, respectively. Phase 3. Targets FLT3 (D835Y) (Cell-free assay); JAK2 (V617F) (Cell-free assay); FLT3 (Cell-free assay); JAK2 (Cell-free assay); TYK2 (Cell-free assay) 14593, In vitro Pacritinib is a potent inhibitor of both wild-type JAK2 and JAK2^V617F mutant (IC50= 19 nM) that is present in high frequencies among patients with MPD. Relative to JAK2, Pacritinib is two-fold less potent against TYK2 (IC50= 50 nM), 23-fold less potent against JAK3 (IC50= 520 nM) and 56-fold less potent against JAK1 (IC50= 1280 nM). Pacritinib effectively permeates cells to modulate signaling pathways downstream of JAK2, whether agonist activated or mutationally activated. Pacritinib induces apoptosis, cell cycle arrest and antiproliferative effects in JAK2^WT- and JAK2^V617F-dependent cells. Pacritinib inhibits cell proliferation of Karpas 1106P and Ba/F3-JAK2^V617F with IC50 of 348 and 160 nM, respectively. Pacritinib inhibits endogenous colony growth derived from erythroid and myeloid progenitors with IC50 of 63 and 53 nM , respectively. SB1518 also inhibits FLT3 and its mutant FLT3-D835Y(IC50= 6 nM ). Pacritinib inhibits FLT3 phosphorylation and downstream STAT, MAPK and PI3K signaling in FLT3-internal-tandem duplication (ITD), FLT3-wt cells and primary AML blast cells. Pacritinib treatment leads to a dose-dependent decrease of pFLT3, pSTAT5, pERK1/2 and pAkt in FLT3-ITD harboring MV4-11 cells with IC50 of 80, 40, 33 and 29 nM , respectively. Treatment of the primary AML blast cells with Pacritinib for 3 h leads to a dose-dependent decrease of pFLT3, pSTAT3 and pSTAT5 with an IC50 below 0.5 μM. Pacritinib induces apoptosis, cell cycle arrest and anti-proliferative effects in FLT3-mutant and FLT3-wt cells. Pacritinib inhibits cell proliferation of FLT3-ITD-harboring cells MV4-11 and primary AML blast cells with IC50s of 47 nM and 0.19-1.3 μM, respectively. In vivo Pacritinib administrated at 150 mg/kg p.o. q.d. to JAK2^V617F-dependent xenograft model, significantly ameliorates splenomegaly and hepatomegaly symptoms, with 60% normalization of spleen weight and 92% normalization of liver weight and is well tolerated without significant weight loss or any hematological toxicities, including thrombocytopenia and anemia. Pacritinib induces dose-dependent inhibition of tumor growth of JAK2^V617F-dependent SET-2 xenograft model (40% for 75 mg/kg and 61% for 150 mg/kg). Pacritinib is efficacious in FLT3-ITD-bearing MV4-11 xenograft models. Pacritinib treated once daily for 21 consecutive days, induces dose-dependent inhibition of tumor growth (38% for 25 mg/kg, 92% for 50 mg/kg and 121% for 100 mg/kg). Complete regression is observed in 3/10 and 8/8 mice for the 50 and 100 mg/kg/day groups, respectively. Cell Research(from reference) Cell lines：Karpas 1106P cells Concentrations：~10 μM Incubation Time：2 days
纯度	≥95%

产品属性

IC50	JAK3, IC50: 520 nM
ALogP	4.547
HBD Count	1
Rotatable Bond	4

关联靶点（人）

STK11 Tchem 丝氨酸/苏氨酸蛋白激酶 STK11(Serine/threonine-protein kinase STK11) (1 活性数据)

点击查看靶蛋白信息： STK11

活性类型	活性值-log(M)	作用机制	期刊	参考文献(PubMed IDs)

FLT3 Tclin 受体型酪氨酸蛋白激酶 FLT3(Receptor-type tyrosine-protein kinase FLT3) (4 活性数据)

点击查看靶蛋白信息： FLT3

活性类型	活性值-log(M)	作用机制	期刊	参考文献(PubMed IDs)

JAK3 Tclin 酪氨酸蛋白激酶JAK3(Tyrosine-protein kinase JAK3) (1 活性数据)

点击查看靶蛋白信息： JAK3

活性类型	活性值-log(M)	作用机制	期刊	参考文献(PubMed IDs)

JAK1 Tclin 酪氨酸蛋白激酶JAK1(Tyrosine-protein kinase JAK1) (1 活性数据)

点击查看靶蛋白信息： JAK1

活性类型	活性值-log(M)	作用机制	期刊	参考文献(PubMed IDs)

Tchem 未表征蛋白 FLJ45252(Uncharacterized protein FLJ45252) (1 活性数据)

点击查看此靶标相关信息

活性类型	活性值-log(M)	作用机制	期刊	参考文献(PubMed IDs)

ACVR1 Tchem 激活素受体 1 型(Activin receptor type-1) (1 活性数据)

点击查看靶蛋白信息： ACVR1

活性类型	活性值-log(M)	作用机制	期刊	参考文献(PubMed IDs)

NQO2 Tchem 核糖二氢烟酰胺脱氢酶[醌](Ribosyldihydronicotinamide dehydrogenase [quinone]) (1 活性数据)

点击查看靶蛋白信息： NQO2

活性类型	活性值-log(M)	作用机制	期刊	参考文献(PubMed IDs)

JAK2 Tclin 酪氨酸蛋白激酶JAK2(Tyrosine-protein kinase JAK2) (5 活性数据)

点击查看靶蛋白信息： JAK2

活性类型	活性值-log(M)	作用机制	期刊	参考文献(PubMed IDs)

名称和识别符

PubChem SID	504770690
分子类型	小分子
IIUPAC Name	(16E)-11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,27-triazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(24),2(27),3,5,8(26),9,11,16,21(25),22-decaene
INCHI	1S/C28H32N4O3/c1-2-13-32(12-1)14-17-35-27-9-8-25-19-24(27)21-34-16-4-3-15-33-20-22-6-5-7-23(18-22)26-10-11-29-28(30-25)31-26/h3-11,18-19H,1-2,12-17,20-21H2,(H,29,30,31)/b4-3+
InChi Key	HWXVIOGONBBTBY-ONEGZZNKSA-N
Smiles	C1CCN(C1)CCOC2=C3COCC=CCOCC4=CC(=CC=C4)C5=NC(=NC=C5)NC(=C3)C=C2
Isomeric SMILES	C1CCN(C1)CCOC2=C3COC/C=C/COCC4=CC(=CC=C4)C5=NC(=NC=C5)NC(=C3)C=C2
PubChem CID	46216796
分子量	472.58

化学和物理性质

溶解性	Solubility (25°C) In vitro DMSO: 11 mg/mL warmed with 50ºC Water: bath (23.27 mM); Water: Insoluble; Ethanol: Insoluble;
DMSO(mg / mL) Max Solubility	11
DMSO(mM) Max Solubility	23.27648229
Water(mg / mL) Max Solubility	＜1
分子量	472.600 g/mol
XLogP3	3.800
氢键供体数Hydrogen Bond Donor Count	1
氢键受体数Hydrogen Bond Acceptor Count	7
可旋转键计数Rotatable Bond Count	4
精确质量Exact Mass	472.247 Da
单同位素质量Monoisotopic Mass	472.247 Da
拓扑极表面积Topological Polar Surface Area	68.700 Å²
重原子数Heavy Atom Count	35
形式电荷Formal Charge	0
复杂度Complexity	644.000
同位素原子数Isotope Atom Count	0
定义的原子立体中心计数Defined Atom Stereocenter Count	0
未定义的原子立体中心计数Undefined Atom Stereocenter Count	0
定义的键立体中心计数Defined Bond Stereocenter Count	1
未定义的键立体中心计数Undefined Bond Stereocenter Count	0
所有立体化学键的总数The total count of all stereochemical bonds	1
共价键合单元计数Covalently-Bonded Unit Count	1

安全和危险性（GHS）

象形图	GHS07
信号词	警告
危险声明	H302: 吞食有害 H317: 可能引起皮肤过敏反应
预防措施声明	P280: 戴防护手套/穿防护服/戴防护眼罩/戴防护面具。

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找到4个结果

批号(Lot Number)	证书类型	货号
J2225648	分析证书	P413904
J2225653	分析证书	P413904
J2225680	分析证书	P413904
J2225730	分析证书	P413904

引用文献

1. William AD, Lee AC, Blanchard S, Poulsen A, Teo EL, Nagaraj H, Tan E, Chen D, Williams M, Sun ET et al.. (2011) Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma.. J Med Chem, 54 (13): (4638-58). [PMID:21604762]
2. Hart S, Goh KC, Novotny-Diermayr V, Hu CY, Hentze H, Tan YC, Madan B, Amalini C, Loh YK, Ong LC et al.. (2011) SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies.. Leukemia, 25 (11): (1751-9). [PMID:21691275]

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货号 (SKU)	包装规格	是否现货
P413904-5mg	5mg	现货
P413904-10mg	10mg	现货
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帕克替尼（SB1518）, 酪氨酸蛋白激酶受体 FLT3 抑制剂

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基本描述

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关联靶点（人）

名称和识别符

化学和物理性质

安全和危险性（GHS）

质检证书（CoA,COO,BSE/TSE 和分析图谱)

引用文献

溶液计算器

摩尔浓度计算器

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