Pacritinib

Pacritinib

Clinical data
Routes of administration	Oral
ATC code	None
Legal status
Legal status	Investigational
Identifiers
IUPAC name (16E)-11-[2-(1-Pyrrolidinyl)ethoxy]-14,19-dioxa-5,7,26-triazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene
Synonyms	SB1518
CAS Number	937272-79-2
PubChem CID	46216796
ChemSpider	28518965
ChEMBL	CHEMBL2035187
Chemical and physical data
Formula	C28H32N4O3
Molar mass	472.58 g/mol
3D model (Jmol)	Interactive image
SMILES c1cc2cc(c1)-c3ccnc(n3)Nc4ccc(c(c4)COC/C=C/COC2)OCCN5CCCC5
InChI InChI=1S/C28H32N4O3/c1-2-13-32(12-1)14-17-35-27-9-8-25-19-24(27)21-34-16-4-3-15-33-20-22-6-5-7-23(18-22)26-10-11-29-28(30-25)31-26/h3-11,18-19H,1-2,12-17,20-21H2,(H,29,30,31)/b4-3+ Key:HWXVIOGONBBTBY-ONEGZZNKSA-N

Pacritinib (INN) is a macrocyclic Janus kinase inhibitor that is being developed for the treatment of myelofibrosis. It mainly inhibits Janus kinase 2 (JAK2) and Fms-like tyrosine kinase 3 (FLT3). The drug was in Phase III clinical trials as of 2013^[update]. The drug was discovered in Singapore at the labs of S*BIO Pte Ltd. It is a potent JAK2 inhibitor with activity of IC₅₀ = 23 nM for the JAK2WT variant and 19 nM for JAK2V617F with very good selectivity against JAK1 and JAK3 (IC₅₀ = 1280 and 520 nM, respectively).

The drug was acquired by Cell Therapeutics, Inc. (CTI) and Baxter International and could effectively address an unmet medical need for patients living with myelofibrosis who face treatment-emergent thrombocytopenia on marketed JAK inhibitors. When Shire Pharmaceuticals purchased Baxalta, a spin-off of Baxter Pharmaceuticals, they halted the development of the drug and ended their partnership with CTI.

The drug was given fast-track status in 2014. In 2016, the FDA placed a full clinical hold on pacritinib due to increased mortality in patients receiving the drug in the "PERSIST-2" trial.