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Activity Type | Activity Value -log(M) | Mechanism of Action | Activity Reference | Publications (PubMed IDs) |
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SKU | Size | Availability | Price | Qty |
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P408148-1ml | 1ml | Available within 4-8 weeks(?) Items will be manufactured post-order and can take 4-8 weeks. Thank you for your patience! | $454.90 |
JAK3 Selective Inhibitors
Specifications & Purity | 10mM in DMSO |
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Storage Temp | Store at -80°C |
Shipped In | Dry ice |
Grade | Moligand™ |
Product Description | 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. Pacritinib is a potent inhibitor of both wild-type JAK2 and JAK2V617F 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 JAK2WT- and JAK2V617F-dependent cells. Pacritinib inhibits cell proliferation of Karpas 1106P and Ba/F3-JAK2V617F 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 JAK2V617F-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 JAK2V617F-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 lines:Ba/F3, Ba/F3-JAK2V617F and Ba/F3-MPLW515L cells Concentrations:~10 μM Incubation Time:2 days Powder Purity:≥95% |
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Canonical SMILES | C1CCN(C1)CCOC2=CC=C3NC4=NC=CC(=N4)C5=CC(=CC=C5)COC\C=C\COCC2=C3 |
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Molecular Weight | 472.58 |
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Solubility | Solubility (25°C) In vitro DMSO: 44.5 mg/mL (200.21 mM); Ethanol: 44.5 mg/mL (200.21 mM); Water: Insoluble; |
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