ROC-325

ROC-325 is a **novel, orally available small molecule autophagy inhibitor** that works by disrupting lysosomal function. Designed as a dimeric compound incorporating structural motifs from hydroxychloroquine (HCQ) and lucanthone, ROC-325 exhibits lysosomal deacidification and blocks the autophagic flux, resulting in the accumulation of autophagosomes and impaired degradation pathways. Compared to HCQ, ROC-325 possesses **markedly enhanced potency** for autophagy inhibition and anticancer effects. Preclinical studies have demonstrated that ROC-325 is active against various tumor cell types, with particular activity in acute myeloid leukemia (AML) and renal cell carcinoma (RCC), and can augment the effects of azacitidine in AML models. Beyond oncology, ROC-325 has shown effectiveness in experimental models of pulmonary hypertension (PH), where it inhibits autophagy, reduces hypoxia-inducible factor (HIF) expression, and enhances nitric oxide production, leading to improvements in right ventricular function and attenuation of vascular remodeling[1][2][3][4][5][6][7][8].