🎯 Drug Targets

Enzyme replacement therapy via L-DOPA supplementation to bypass reduced TH activity

Enzyme inhibition — blocking ACSL4 prevents incorporation of PUFAs into membrane phospholipids, reducing ferroptosis susceptibility

Enzyme activation — enhancing SIRT3 deacetylase activity restores mitochondrial protein function and reduces oxidative stress

Competitive inhibitors of PARP1 enzymatic activity blocking DNA repair

Small molecule inhibitor of mutant IDH2 enzyme activity

Small molecule inhibitor of acyl-CoA:cholesterol acyltransferase activity

Small molecule inhibitors blocking leukotriene synthesis

Monoclonal antibody targeting or small molecule inhibitor of NAD+ consuming activity

Small molecule inhibitor of cyclic dinucleotide synthesis

Small molecule inhibitors of transglutaminase enzymatic activity

Small molecule inhibitors of lipoxygenase enzymatic activity

Small molecule inhibitor of glucose phosphorylation

Small molecule inhibition of lysyl oxidase enzymatic activity

Small molecule competitive inhibitors of NAD+ biosynthesis enzyme

Small molecule inhibitor of prolyl isomerase activity and HSP90 co-chaperone function

Small molecule inhibitor of cytosolic phospholipase A2 enzymatic activity

Small molecule inhibitor or activator of peroxidase activity

Small molecule inhibitors targeting the active site iron and substrate binding

Small molecule inhibitors of VCP ATPase activity affecting protein quality control

Small molecule inhibitor of triglyceride synthesis enzyme

Small molecule activator of cholesterol 24-hydroxylase enhancing brain cholesterol turnover

Drugs targeting COX4I1 pathway would enhance electron transport chain efficiency or stabilize complex IV assembly, improving ATP production and reducing oxidative stress in mitochondria. These agents work by either promoting mitochondrial bioenergetics, acting as electron donors/acceptors, or preventing complex IV degradation in diseases with impaired oxidative phosphorylation.

Small molecule inhibitor of calcium-independent phospholipase A2 activity

FUT8 inhibitors would block the addition of core fucose to N-linked glycans on proteins, modulating antibody-dependent cellular cytotoxicity (ADCC) and potentially reducing pathological protein aggregation in neurodegenerative diseases. By preventing fucosylation, these drugs could enhance immune effector function or alter protein conformational stability and clearance.

ST6GAL1 inhibitors would block the addition of α2,6-linked sialic acids to N-glycans on cell surface proteins, altering immune cell recognition and potentially enhancing anti-tumor immunity or modulating inflammatory responses. This glycosylation modification is crucial for immune evasion in cancer and autoimmune disease pathogenesis.

Small molecule inhibitor or modulator of sphingomyelinase activity

SGMS2 inhibitors would block the enzymatic transfer of phosphocholine to ceramide, reducing sphingomyelin biosynthesis and altering membrane composition and cellular signaling. This modulation could reduce pathological lipid accumulation and restore normal cell membrane dynamics in diseases characterized by sphingolipid dysregulation.

Small molecule inhibitor or activator of nuclease activity

CERS2 inhibitors would reduce the enzymatic synthesis of very long-chain ceramides by blocking the condensation of serine and palmitoyl-CoA, thereby decreasing ceramide-mediated neuroinflammation and apoptosis implicated in neurodegenerative pathology. This modulation of the ceramide signaling cascade may provide neuroprotective effects in Alzheimer's disease and related neurodegenerative conditions.

Therapeutic agents targeting SETX would likely enhance RNA helicase activity or stabilize protein function to improve transcriptional regulation and DNA repair, or alternatively inhibit aberrant signaling pathways triggered by SETX dysfunction in neuronal tissues. Small molecule stabilizers or gene therapy approaches could restore deficient helicase activity in ataxia-causing mutations.

Small molecule enzyme inhibitors targeting the catalytic domain

Small molecule inhibitor preventing peripheral conversion of levodopa to dopamine

SGMS1 inhibitors would block the transfer of phosphocholine from phosphatidylcholine to ceramide, reducing sphingomyelin synthesis and potentially decreasing membrane rigidity and inflammatory signaling. This mechanism could modulate membrane-dependent cellular processes and may have therapeutic effects in lipid storage disorders and metabolic diseases.

ST8SIA1 inhibitors would block the synthesis of polysialic acid chains on NCAM, reducing neural cell plasticity and potentially modulating neuroinflammatory responses. This mechanism could be therapeutically relevant for neurodevelopmental disorders or neuroinflammatory conditions where excessive polysialylation contributes to pathology.

Inhibitors of ST3GAL2 would block the transfer of sialic acid (α-2,3 linkage) to galactose residues on glycoproteins and glycolipids, reducing cell surface sialylation and potentially enhancing immune recognition of cancer cells or modulating inflammatory responses. Alternatively, activators or substrate analogs could enhance sialylation for immune tolerance in inflammatory conditions.