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Pacritinib (SB1518)

Catalog No.
B1589
JAK2/FLT3 inhibitor
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$390.00
In stock
5mg
$158.00
In stock
10mg
$284.00
In stock
25mg
$428.00
In stock
50mg
$1,140.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

Pacritinib is a small molecule inhibitor of Janus kinase 2/Fms-like tyrosine kinase-3 (JAK2/FLT3) with IC50 values of 23nM, 19nM and 22nM, respectively for JAK2WT, JAK2V617F and FLT3 [1].

Pacritinib inhibits the JAK2-mediated production of p-STAT5 and p-STAT3 in Ba/F3 cells and the production of p-FLT3 and p-STAT5 in MV4-11 cells. It is less active against CYP3A4 and has good selectivity and microsomal stability. Pacritinib is proved to be high permeable in a Caco-2 bidirectional permeability assay. Additionally, pacritinib has a good oral bioavailability. In the Ba/F3-JAK2V617F mouse allograft, 150mg/kg treatment of pacritinib significantly alleviates the disease symptoms. In the MV4-11 xenografts, 50mg/kg and 100 mg/kg pacritinib treatments both show a significantly increased median survival of 55 days [1].

References:
[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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt472.58
Cas No.937272-79-2
FormulaC28H32N4O3
Solubilityinsoluble in EtOH; insoluble in H2O; ≥11.05 mg/mL in DMSO with gentle warming
Chemical NameAN2728;AN 2728
SDFDownload SDF
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]
Shipping ConditionEvaluation sample solution: ship with blue ice. All other available sizes: ship with RT, or blue ice upon request.
General tipsFor obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.

Protocol

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 pJAK2V617F in 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.

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