Jaktinib (DB17545): A Comprehensive Pharmacological and Clinical Monograph of a Novel Dual JAK/ACVR1 Inhibitor

Executive Summary

Jaktinib (DrugBank ID: DB17545) is an orally administered small molecule Janus kinase (JAK) inhibitor developed by Suzhou Zelgen Biopharmaceuticals. Chemically, it is a deuterated analog of momelotinib, a strategic modification intended to optimize its pharmacokinetic profile. Jaktinib's primary mechanism of action involves the inhibition of the JAK-STAT signaling pathway, a critical mediator of cellular processes in hematopoiesis and immunity. It exhibits a distinct inhibitory profile with potent activity against JAK2 and TYK2. Critically, Jaktinib also inhibits Activin A receptor, type 1 (ACVR1), a key regulator of hepcidin and iron metabolism. This dual mechanism confers a unique clinical profile, enabling the simultaneous management of myeloproliferation, constitutional symptoms, and disease-related anemia—a significant challenge in the treatment of myelofibrosis (MF).

The clinical development program for Jaktinib has demonstrated robust efficacy and a manageable safety profile across a range of hematologic and inflammatory conditions. In May 2025, Jaktinib was approved by China's National Medical Products Administration (NMPA) for the treatment of intermediate- to high-risk myelofibrosis. This approval was based on the pivotal Phase III ZGJAK016 trial, in which Jaktinib demonstrated statistically significant superiority over the standard-of-care agent hydroxyurea in reducing spleen volume, while also showing improvements in constitutional symptoms and anemia with a more favorable hematologic safety profile. Furthermore, Jaktinib has shown significant clinical activity in patients with MF who are intolerant, refractory, or have relapsed after treatment with ruxolitinib.