HOSU-53 (JBZ-001) is a potent and selective inhibitor of DHODH with IC50 of 0.95 nM (hDHODH), exhibits potent antileukemic activity.
HOSU-53 has similar inhibitory potency across against mouse, rat, and dog DHODH enzymes.
HOSU-53 shows no alternative-target activity at 10 μM against a panel of approximately 450 human kinases
HOSU-53 significantly reduced oxidative metabolism in T cells both during and after activation, while selectively suppressing inflammatory cytokine production in de novo activated, but not previously activated, T cells.
HOSU-53 treatment limited GVHD severity, decreased pathogenic Th1 and Th17 response, and preserved beneficial GVL effects in xenogeneic model.
HOSU-53 in combination with anti-CD47 therapy results in long-term disease-free survival in the MOLM-13 CDX AML in vivo model.
HOSU-53 shows in vivo efficacy superior to other DHODH inhibitors and exceptional pharmaceutical properties for clinical advancement.