SB1518 (Pacritinib)

• CAT Number: I005573
• CAS Number: 937272-79-2
• Molecular Formula: C₂₈H₃₂N₄O₃
• Molecular Weight: 472.58
• Purity: ≥95%
• Target: JAK2; FLT3
• Solubility: DMSO: ＜ 4.7 mg/mL
• Storage: -20°C
• IC50: 23 nM (JAK2 wt); 22 nM (FLT3)
• 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+
• InChIKey: HWXVIOGONBBTBY-ONEGZZNKSA-N
• SMILES: C1CCN(C1)CCOC2=C3COCC=CCOCC4=CC=CC(=C4)C5=NC(=NC=C5)NC(=C3)C=C2

Pacritinib(CAT: I005573) is a potent and selective inhibitor of Janus kinase 2 (JAK2). JAK2 is a tyrosine kinase involved in the signaling pathway of various cytokines and growth factors. By inhibiting JAK2, pacritinib can interfere with the abnormal signaling that occurs in certain diseases, particularly myeloproliferative neoplasms (MPNs) such as myelofibrosis. Pacritinib has shown efficacy in reducing spleen size and alleviating symptoms associated with myelofibrosis.

Reference

1. Future Oncol. 2015;11(20):2819-30. doi: 10.2217/fon.15.200. Epub 2015 Sep 14.
A comprehensive review of pacritinib in myelofibrosis.
Verstovsek S(1), Komrokji RS(2).
Author information:
(1)Department of Leukemia, The University of Texas MD Anderson Cancer Center,
1515 Holcombe Boulevard, Houston, TX 77030, USA.
(2)Malignant Hematology Department, Moffitt Cancer Center, 12902 Magnolia Drive,
Tampa, FL 33612, USA.
The first-in-class JAK1/JAK2 inhibitor ruxolitinib inhibits JAK/STAT signaling,
inducing durable reductions in splenomegaly and constitutional symptoms in
patients with myelofibrosis. However, the association of ruxolitinib therapy with
myelosuppression indicates the continued need for optimal treatment choices in
myelofibrosis. Pacritinib, a dual JAK2 and FLT3 inhibitor, improves
disease-related symptoms and signs with manageable gastrointestinal toxicity in
patients with myelofibrosis with splenomegaly and high-risk features, without
causing overt myelosuppression, and therefore may provide an important treatment
option for a range of patients with myelofibrosis. This article examines the role
of JAK2 and FLT3 signaling in myelofibrosis and provides an overview of the
clinical development of pacritinib as a new therapy for myelofibrosis.
2. J Blood Med. 2014 Aug 19;5:143-52. doi: 10.2147/JBM.S51253. eCollection 2014.
Profile of pacritinib and its potential in the treatment of hematologic
disorders.
Hatzimichael E(1), Tsolas E(1), Briasoulis E(1).
Author information:
(1)Department of Haematology, University Hospital of Ioannina, Ioannina, Greece.
Pacritinib (previously known as SB-1518) is an innovative selective inhibitor of
Janus kinase 2 and FMS-related tyrosine kinase 3 providing potential in the
treatment of hematological malignancies such as myeloproliferative neoplasias,
acute myeloid leukemia, and various lymphomas. Pacritinib has potent
antiproliferative activity in Janus kinase 2 and/or FMS-related tyrosine kinase 3
activity-dependent cell lines and an ability to promote apoptosis and inhibit the
signal transducers and activators of transcription (STAT) pathway.
Pharmacokinetic studies have indicated a good per os bioavailability and
favorable kinetic parameters. To date, promising results have been produced in
five completed early-phase clinical trials in which pacritinib has been studied.
Pacritinib displayed interesting activity and an acceptable safety profile, with
mild to moderate gastrointestinal disorders being its most common adverse
effects.