| Identification | Back Directory | [Name]
PACRITINIB | [CAS]
937272-79-2 | [Synonyms]
SB1518
CS-914
PACRITINIB
Pacritinib, >=98%
SB1518(Pacritinib)
Pacritinib (SB1518)
PACRITINIB USP/EP/BP
SB1518; SB 1518; SB-1518
SB1518; SB 1518; SB-1518; PACRITINIB.
(16E)-11-[2-(1-Pyrrolidinyl)ethoxy]-14,19-dioxa-5,7,27-triazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2,4,6(27),8,10,12(26),16,21,23-decaene
14,19-Dioxa-5,7,27-triazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(25),2,4,6(27),8,10,12(26),16,21,23-decaene, 11-[2-(1-pyrrolidinyl)ethoxy]-, (16E)-
16E)-11-[2-(1-Pyrrolidinyl)ethoxy]-14,19-dioxa-5,7,27-triazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2,4,6(27),8,10,12(26),16,21,23-decaene Pacritinib (SB1518) | [Molecular Formula]
C28H32N4O3 | [MDL Number]
MFCD22572772 | [MOL File]
937272-79-2.mol | [Molecular Weight]
472.59 |
| Chemical Properties | Back Directory | [Boiling point ]
694.3±65.0 °C(Predicted) | [density ]
1.22±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:5.0(Max Conc. mg/mL);10.6(Max Conc. mM) | [form ]
A crystalline solid | [pka]
9.56±0.20(Predicted) |
| Hazard Information | Back Directory | [Uses]
Pacritinib is a JAK2/FLT3 inhibitor used in the treatment of acute myeloid leukemia showing significant tumor growth inhibition and lung metastasis. | [Mechanism of action]
Pacritinib competes with JAK2 for ATP binding, which may result in inhibition of JAK2 activation, inhibition of the JAK-STAT signaling pathway, and so caspase-dependent apoptosis. | [Enzyme inhibitor]
This pyrimidine-based macrocycle and potent protein kinase inhibitor (FW
= 472.59 g/mol; CAS 937272-79-2; Solubility: 11 mg/mL DMSO), also
known as SB1518, selectively targets Janus Kinase 2 (or JAK2; IC50 = 23
nM) and Fms-Like Tyrosine Kinase-3 (or FLT3; IC50 = 22 nM), with values
of 1280 and 522 nM for JAK1 and JAK3. FLT3 is genetically altered in up
to 35% of acute myeloblastic leukemias, making it an attractive target for
AML patients. Pacritinib has potent anti-proliferative effects on myeloid
and lymphoid cell lines driven by mutant or wild-type JAK2 or FLT3,
resulting from cell cycle arrest and induction of apoptosis. SB1518 has
favorable pharmacokinetic properties after oral dosing in mice, is well
tolerated and significantly reduces splenomegaly and hepatomegaly in a
JAK2 (Val-617-Phe) -driven disease model. Primary Mode of Inhibitory
Action: Upregulation of JAK2 in FLT3-TKI-resistant AML cells was
identified as a potential mechanism of resistance to selective FLT3
inhibition. This resistance could be overcome by pacritinib’s combined
inhibition of FLT3 and JAK2 in this cellular model. Pacritinib potently
inhibits FLT3 auto-phosphorylation and downstream STAT5, MAPK and
PI3K signaling pathways in AML cell lines with highest potency against
cells harboring FLT3-ITD mutations. Blockade of FLT3 signaling was
also demonstrated in primary AML blasts treated ex vivo with pacritinib. In
both cell lines and primary blasts, pacritinib treatment led to the induction
of G1 arrest, inhibition of cell proliferation, as well as caspase-dependent
apoptosis. The anti-proliferative effects of pacritinib on the FLT3-ITD
harboring cell lines MV4-11 (IC50 = 47 nM) and MOLM-13 (IC50 = 67 nM),
which have been reported previously,16 are in the same range as the
inhibition of intracellular FLT3 signalling. |
|
| Company Name: |
The Pure Chem
|
| Tel: |
+91-9152957755 +91-9152957755 |
| Website: |
www.thepurechem.com |
|