Pacritinib is an orally active kinase inhibitor developed for the treatment of myelofibrosis, particularly patients with intermediate- or high-risk primary or secondary myelofibrosis and severe thrombocytopenia. The commercially established pharmaceutical form is pacritinib citrate, which is the active pharmaceutical ingredient form used in VONJO capsules. The current FDA prescribing information identifies VONJO as containing pacritinib citrate and gives the molecular weight of the citrate salt as 664.7 g/mol, compared with 472.59 g/mol for the free base.
Sobi markets VONJO in the United States for adults with intermediate- or high-risk primary or secondary myelofibrosis with a platelet count below 50 × 10⁹/L. The current FDA label was revised in July 2026.
Pacritinib free base has the molecular formula C28H32N4O3, CAS number 937272-79-2, and molecular weight 472.59 g/mol. Pacritinib citrate has the molecular formula C34H40N4O10, CAS number 1228923-42-9, and molecular weight 664.7 g/mol. PubChem identifies pacritinib citrate as the citrate salt of pacritinib.
Pacritinib citrate chemical identifiers:
Pacritinib is a multikinase inhibitor with activity against JAK2, mutant JAK2V617F, FLT3, IRAK1, and ACVR1/ALK2. The FDA label specifically notes that pacritinib does not inhibit JAK1 at clinically relevant concentrations and has greater inhibitory activity against JAK2 than JAK3 and TYK2.
The JAK2 pathway is particularly relevant to myelofibrosis because abnormal JAK-STAT signaling contributes to the disease process. By inhibiting JAK2-associated signaling, pacritinib can reduce signaling pathways involved in abnormal hematopoietic activity and disease-associated splenic enlargement.
Pacritinib also inhibits IRAK1 and ACVR1/ALK2, providing a kinase-inhibition profile that differs from several other JAK-directed therapies.
Pacritinib is primarily associated with pharmaceutical development and manufacturing for myelofibrosis therapy.
Key application areas include:
The current U.S. indication specifically covers adults with primary or secondary myelofibrosis and platelet counts below 50 × 10⁹/L.
Myelofibrosis is a chronic myeloproliferative neoplasm characterized by abnormal bone-marrow function, fibrosis, extramedullary hematopoiesis and splenomegaly. Treatment selection can become challenging when patients have very low platelet counts.
Pacritinib is particularly important in this treatment setting because its approved indication specifically addresses myelofibrosis patients with platelet counts below 50 × 10⁹/L. The FDA-approved regimen is 200 mg twice daily for the indicated patient population.
Pacritinib demonstrates activity against several clinically relevant kinase targets.
Research data report inhibitory activity against:
These values are biochemical research measurements and should not be interpreted as pharmaceutical release specifications.
The FDA characterization additionally identifies activity against IRAK1 and ACVR1/ALK2.
Pacritinib citrate is a chemically synthesized pharmaceutical active substance. An EMA European GMP database entry specifically identifies pacritinib citrate, CAS 1228923-42-9, under active-substance manufacturing activities and includes chemical synthesis, purification/salt-formation and physical/chemical quality-control categories.
Quality-focused production of pacritinib citrate requires appropriate control of:
Because publicly accessible regulatory documents do not provide a complete current public API release specification for every CMS field, numerical acceptance criteria should not be invented. Product-specific limits should be taken from the applicable approved specification and Certificate of Analysis.
Pacritinib citrate is available as a research and pharmaceutical-development material. A commercial research reference reports 99.68% purity for a particular pacritinib citrate product; this is a product-specific reference value and should not be represented as a universal pharmacopoeial API assay limit.
For pharmaceutical API manufacturing, analytical testing may include chromatographic purity, identity testing and physicochemical characterization. Where an official public numerical pharmacopoeial limit is unavailable, the finished API should be controlled against its approved manufacturer specification rather than an invented generic value.
Pacritinib citrate is reported as a solid ranging from light yellow to yellow in a research reference.
A research supplier recommends storage at 4°C in sealed conditions away from moisture, while the appropriate pharmaceutical API storage conditions should ultimately follow the validated stability data and approved product specification.
According to the current FDA prescribing information, pacritinib reaches maximum plasma concentration approximately 4–5 hours after administration. Plasma protein binding is approximately 98.8%. The drug is predominantly metabolized by CYP3A4, and the two major metabolites M1 and M2 account for approximately 9.6% and 10.5% of parent-drug exposure, respectively.
The reported effective half-life is approximately 27.7 hours. Following radiolabeled administration, approximately 87% of recovered radioactivity was found in feces and 6% in urine.
Pacritinib citrate is relevant to pharmaceutical companies, analytical laboratories and drug-development programs working with targeted kinase inhibitors and hematological oncology products.
Typical development activities may include:
Pacritinib citrate is also used in research investigating myelofibrosis and acute myeloid leukemia pathways.
VONJO (pacritinib) received its initial U.S. approval in 2022. The current FDA label identifies it as a kinase inhibitor and specifies its indication for adults with intermediate- or high-risk primary or secondary myelofibrosis with platelet counts below 50 × 10⁹/L.
The current recommended dosage in the FDA labeling is 200 mg orally twice daily. The dosage form is a 100 mg capsule.
A pharmaceutical-grade pacritinib citrate manufacturer should maintain controlled synthesis, purification, salt formation, analytical testing, packaging and stability programs consistent with applicable GMP requirements.
Important documentation for commercial API qualification can include:
Pacritinib citrate is specifically identified in an EMA GMP database record as an active substance subject to GMP inspection activities.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.2% |
| Individual Impurity | NMT 0.5% |
| Water Content | NMT 1.0% |