Pacritinib(SB1518)

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Pacritinib(SB1518)

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

937272-79-2

包装与价格：

包装	价格(元)
10mM (in 1mL DMSO)	电议
5mg	电议
10mg	电议
25mg	电议
50mg	电议

产品介绍

化学性质

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	472.58
Cas No.	937272-79-2
Formula	C₂₈H₃₂N₄O₃
Solubility	insoluble in EtOH; insoluble in H2O; ≥11.05 mg/mL in DMSO with gentle warming
Chemical Name	AN2728;AN 2728
Canonical SMILES	[H]C1([H])N(C([H])([H])C([H])([H])OC(C([H])=C2[H])=C(C([H])([H])OC([H])([H])/C([H])=C([H])\C([H])([H])OC([H])([H])C3=C([H])C4=C([H])C([H])=C3[H])C([H])=C2N([H])C5=NC([H])=C([H])C4=N5)C([H])([H])C([H])([H])C1([H])[H]
运输条件	蓝冰运输或根据您的需求运输。
一般建议	为了使其更好的溶解，请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。

资料参考

Pacritinib是一种Janus激酶2/Fms样酪氨酸激酶-3(JAK2/FLT3)的小分子抑制剂,对JAK2WT\JAK2V617F和FLT3的IC50值分别为23 nM\19 nM和22 nM[1].

Pacritinib可在Ba/F3细胞中抑制JAK2介导的p-STAT5和p-STAT3的生成,也可在MV4-11细胞中抑制p-FLT3和p-STAT5的生成.该物质对CYP3A4的活性较低,具有较好的选择性和微粒体稳定性.Pacritinib在Caco-2双向透过性试验中表现出较高的透过性.此外,pacritinib具有良好的口服生物可利用度.在Ba/F3-JAK2V617F小鼠同种移植物中,150 mg/kg的pacritinib治疗可显著减缓疾病症状.在MV4-11异种移植物中,50 mg/kg和100 mg/kg的pacritinib疗法均能显著提高存活时间,中位数为55天[1].

参考文献：
[1] William AD, Lee AC, Blanchard S, Poulsen A, Teo EL, Nagaraj H, Tan E, Chen D, Williams M, Sun ET, Goh KC, Ong WC, Goh SK, Hart S, Jayaraman R, Pasha MK, Ethirajulu K, Wood JM, Dymock BW. 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. 2011 Jul 14;54(13):4638-58.

试验操作

Cell experiment:[1]
Cell lines	Karpas 1106p cells
Reaction Conditions	3 ~ 48 h incubation
Applications	Exposure of Karpas 1106P cells to pacritinib (0 ~ 1000 nM) for 3 h led to attenuation of the basal level of pSTAT3. Pacritinib induced apoptosis (EC50 = 1.122 μM; 16 h), cell cycle arrest (1 × and 3 × IC50; 24 h) and inhibition of proliferation (IC50 = 0.348 μM; 48 h) in Karpas 1106P cells.
Animal experiment:[1]
Animal models	SET-2 tumor-bearing mice
Dosage form	75 and 150 mg/kg Administered by oral gavage
Applications	Pacritinib increased pJAK2^V617Fin the tumor tissue, but simultaneously inhibited phosphorylation of STAT5 in a dose-dependent manner, which indicated effective blockade of JAK2 signaling. Pacritinib treatment for 18 consecutive days induced dose-dependent inhibition of tumor growth (40% for 75 mg/kg and 61% for 150 mg/kg).
Note	The technical data provided above is for reference only.
	References: 1. Hart S, Goh KC, Novotny-Diermayr V, et al. SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies. Leukemia, 2011, 25(11): 1751-1759.