CTPI-2

CTPI-2 is a third-generation mitochondrial citrate carrier SLC25A1 inhibitor with a K_D of 3.5 μM. CTPI-2 inhibits glycolysis, PPARγ, and its downstream target the glucose transporter GLUT4. CTPI-2 halts salient alterations of NASH reverting steatosis, preventing the evolution to steatohepatitis, reducing inflammatory macrophage infiltration in the liver and adipose tissue, and starkly mitigating obesity induced by a high-fat diet. Antitumor activity^[1][2]. IC50 & Target: KD: 3.5 μM (SLC25A1)^[1] In Vivo: CTPI-2 is a unique regulator of glycolysis that limits the metabolic plasticity of cancer stem cells (CSCs). CTPI-2 (26 mg/kg; i.p.) inhibits tumor growth in in vivo models of non-small cell lung cancer (NSCLC)^[1].
CTPI-2 (50 mg/kg; i.p.; alternate days for 12 weeks) completely averts weight gain in the prevention study and leads to significant weight loss in the reversion study^[2].
CTPI-2 prevents steatohepatitis and normalizes glucose tolerance. CTPI-2 lowers the levels of circulating IL-6 while increasing anti-inflammatory IL-4 and IL-10 and also reduced the monocyte chemoattractant protein-1 and monokine-induced by interferon-γ that attract neutrophils and monocytes. CTPI-2 regulates the citrate pool, the lipogenic and the gluconeogenic pathways^[2].