G6PDi-1

G6PDi-1 is a small molecule inhibitor of glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme of the pentose phosphate pathway (PPP). By blocking G6PD activity, G6PDi-1 disrupts the production of NADPH and ribose-5-phosphate, which are critical for maintaining cellular redox balance and supporting nucleotide biosynthesis. In preclinical studies of renal cell carcinoma (RCC), G6PDi-1 has demonstrated the ability to impair tumor cell viability, migration, and clonogenic capacity, particularly in clear cell RCC (ccRCC) models that exhibit high G6PD dependency. It is being investigated as a potential therapeutic agent to address therapeutic resistance in aggressive kidney cancers and as a targeted treatment for tumors where G6PD serves as a biomarker of vulnerability.