Type Ia Congenital Disorders of Glycosylation (CDG-Ia) is the most common form of Congenital Disorders of Glycosylation, an autosomal recessive defects in the synthesis of N-linked oligosaccharide chains caused by defects in the PMM2 gene. PMM2 encodes phosphomannomutase 2, which is responsible for the conversion of mannose-6-P [Man-6-P] to Man-1-P. Currently, there is no treatment for CDG-Ia patients. The current project aimed to identify novel non-competitive inhibitors of PMI that can be used as potential therapeutic treatments for these patients. The developed probe ML089 (CID-22416235) inhibits human phosphomannose isomerase (PMI) and may inhibit other PMI orthologs due to the highly conserved nature of the enzyme. The probe is membrane permeable and, as a result ,can also be used to inhibit PMI in living cells. Thus, the probe may serve as a therapeutic treatment for CDG-Ia patients by blocking the catabolism of Man-6-P in cells, thereby redirecting it towards protein glycosylation using this residual PMM2 activity.