Pacritinib

• CAT Number: I005573
• CAS Number: 937272-79-2
• Molecular Formula: C28H32N4O3
• Molecular Weight: 472.58
• Purity: 97%
• Synonyms: SB1518
• Target: JAK-3; FLT3
• Target Protein: P36888
• Solubility: DMSO: ＜ 4.7 mg/mL
• Appearance: Solid
• Storage: Dry, dark and at 2 - 8 °C for six months or -20°C for two years.
• IC50: FLT3D835Y：6 nM (IC50); JAK3：520 nM (IC50)
• IUPAC Name: (16E)-11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,27-triazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(24),2(27),3,5,8(26),9,11,16,21(25),22-decaene
• 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=C3COC/C=C/COCC4=CC(=CC=C4)C5=NC(=NC=C5)NC(=C3)C=C2

Pacritinib（Cat No.:I005573）is an oral kinase inhibitor specifically designed to target Janus kinase 2 (JAK2) and FLT3, key drivers in the development of myeloproliferative disorders. It is primarily used for the treatment of myelofibrosis, particularly in patients with low platelet counts. By inhibiting JAK2, Pacritinib reduces abnormal cell proliferation and alleviates symptoms such as spleen enlargement and anemia. Unlike other JAK inhibitors, Pacritinib shows efficacy with minimal impact on platelet levels, making it a valuable option for patients with thrombocytopenia. Its unique profile addresses an unmet need in myelofibrosis treatment.

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.