Pacritinib (SB1518) 是一种有效的野生型 JAK2 和 JAK2^V617F 突变型抑制剂，IC₅₀ 分别为 23 nM 和 19 nM。Pacritinib 也抑制 FLT3 及其突变型 FLT3^D835Y，IC₅₀ 分别为 22 nM 和 6 nM。

Pacritinib (SB1518) is a potent inhibitor of both wild-type JAK2 (IC 50 =23 nM) and JAK2 mutant (IC 50 =19 nM). Pacritinib also inhibits FLT3 (IC 50 =22 nM) and its mutant FLT3 (IC 50 =6 nM).

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JAK2 19 nM (IC50) JAK2 23 nM (IC50

Relative to JAK2, Pacritinib (SB1518) 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). The rest of the evaluated kinases show <30% inhibition when tested against 100 nM Pacritinib at adenosine triphosphate concentrations equivalent to its Michaelis constant (Km). Pacritinib inhibits MV4-11 and MOLM-13 cells (both of which are cell lines derived from human acute myeloid leukemias driven by an FLT3 ITD mutation) with IC50 of 47 and 67 nM, respectively. Pacritinib inhibits Karpas 1106P and Ba/F3-JAK2 cells (which are cell lines dependent on JAK2 signaling) with IC50 of 348 and 160 nM, respectively. FLT3-ITD harboring MV4-11 cells are treated for 3 h with different concentrations of Pacritinib (SB1518) and pFLT3,

For evaluation of efficacy in the Ba/F3-JAK2 engraftment model, mice are treated with Pacritinib (SB1518) at doses of 50 or 150 mg/kg p.o. q.d. for 13 days, with drug dosing starting 4 days after cell inoculation. At study termination, the vehicle control mice exhibit splenomegaly and hepatomegaly (~7- and 1.3-fold, respectively), reminiscent of the symptoms found in patients with symptomatic myelofibrosis. SB1518 treatment at 150 mg/kg p.o. q.d. significantly ameliorates all these symptoms, with 60% (±9%) normalization of spleen weight and 92% (±5%) normalization of liver weight and is well tolerated without significant weight loss or any hematological toxicities, including thrombocytopenia and anemia. In rats, Pacritinib (SB1518) shows moderately fast absorption (t max =4 h), with a peak concentration of 114 ng/mL, AUC of 599 ng?h/mL, and a terminal half-life of ~6

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Hart S, et al. SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies. Leukemia. 2011 Nov;25(11):1751-9.
[2]. Hart S, et al. Pacritinib (SB1518), a JAK2/FLT3 inhibitor for the treatment of acute myeloid leukemia. Blood Cancer J. 2011 Nov;1(11):e44.

In Vitro: DMSO : 5 mg/mL (10.58 mM; Need ultrasonic)配制储备液