Preferred Label : Pacritinib Hydrochloride;
NCIt synonyms : 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)-, Hydrochloride (1:1);
NCIt definition : The hydrochloride salt form of pacritinib, an orally bioavailable inhibitor of Janus
kinase 2 (JAK2), the JAK2 mutant JAK2V617F and FMS-like tyrosine kinase 3 (FLT3; CD135;
STK1; FLK2), with potential antineoplastic activity. Upon oral administration of pacritinib
hydrochloride, pacritinib competes with JAK2 and the JAK2 mutant JAK2V617F for ATP
binding, which may result in inhibition of JAK2 activation, inhibition of the JAK-signal
transducer and activator of transcription (STAT) signaling pathway, and the induction
of apoptosis. In addition, pacritinib targets, binds to and inhibits the activity
of FLT3. This inhibits FLT3-mediated signaling and the proliferation of FLT3-expressing
cancer cells. JAK2, often upregulated or mutated in a variety of cancer cells, plays
a key role in tumor cell proliferation and survival. The JAK2V617F gain-of-function
mutation involves a valine-to-phenylalanine modification at position 617. The JAK-STAT
signaling pathway is a major mediator of cytokine activity. FLT3, a class III receptor
tyrosine kinase (RTK), is overexpressed or mutated in most B-lineage neoplasms and
in acute myeloid leukemias. In addition, JAK2 and FLT3 play a key role in the regulation
of the inflammatory response and dendritic cell (DC) proliferation, differentiation
and function. Inhibition of JAK2- and FLT3-mediated signaling may suppress the generation
and differentiation of DCs, and may regulate inflammatory and immune responses.;
UNII : XV36F0JG6L;
CAS number : 1228923-43-0;
NCI Metathesaurus CUI : CL1778496;
Origin ID : C185888;
UMLS CUI : C5667130;
Semantic type(s)
- concept_is_in_subset
- has_free_acid_or_base_form
- has_target
- is_salt_form_of
