ITPKB Antibody

Immune Cell Regulation

ITPKB is essential for mature T cell survival and calcium signaling. Genetic deletion or pharmacological inhibition (e.g., GNF362) elevates intracellular calcium, inducing apoptosis via FasL and Bim upregulation. This mechanism blocks T-cell-dependent antibody responses and mitigates autoimmune arthritis in preclinical models .

Neurodegeneration

ITPKB protects against α-synuclein aggregation in Parkinson’s disease (PD). Knockdown or inhibition increases mitochondrial calcium, impairing autophagy and exacerbating α-synuclein pathology. Restoring ITPKB activity reduces ER-to-mitochondria calcium flux, highlighting its therapeutic potential .

Cancer Therapeutics

In glioblastoma (GBM), ITPKB stabilizes reactive oxygen species (ROS) homeostasis, conferring temozolomide (TMZ) resistance. Suppressing ITPKB via genetic knockout or GNF362 enhances TMZ sensitivity by increasing ROS and apoptosis. Trim25-mediated ITPKB ubiquitination regulates this process, making ITPKB a target for overcoming chemoresistance .

Functional Insights from Studies

Mechanistic Role of ITPKB

• Calcium Signaling: ITPKB-generated IP₄ inhibits Orai1/Stim1 calcium channels, preventing excessive Ca²⁺ influx and apoptosis .

• Disease Modulation:

  • In PD, ITPKB loss disrupts mitochondrial respiration and autophagy .

  • In cancer, ITPKB stabilizes ROS balance, promoting chemoresistance .

Therapeutic Potential

The ITPKB inhibitor GNF362 has shown efficacy in preclinical models:

• Blocks T cell-driven arthritis .

• Reduces α-synuclein aggregation .

• Reverses TMZ resistance in glioblastoma .