Pacritinib (SB1518)
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.
| 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 |
| SDF | Download 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 Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[1] | |
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Cell lines |
Karpas 1106p cells |
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Reaction Conditions |
3 ~ 48 h incubation |
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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] | |
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Animal models |
SET-2 tumor-bearing mice |
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Dosage form |
75 and 150 mg/kg Administered by oral gavage |
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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). |
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Note |
The technical data provided above is for reference only. |
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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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Quality Control & MSDS
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Chemical structure
