The majority of tryptophan metabolism passes through the kynurenine pathway. Metabolic imbalances in this pathway are implicated disease. KYNA, transaminated by the kynurenine aminotransferase (KAT) enzymes, is elevated in patients with schizophrenia. Schizophrenia is a neuropsychiatric disease with limited treatment options and debilitating symptoms. Glutamatergic systems are thought to have a significant role in its pathogenesis, providing a basis by which KYNA, an endogenous glutamate antagonist, is implicated in the disease. Four pyridoxal 5’-phosphate-dependent homologues of KAT are reported. KAT-II is primarily responsible for KYNA production in the human brain. KAT-II inhibitors reduce KYNA production, increase neurotransmitter release and elicit pro-cognitive effects, indicative of their potential as novel therapies in treating schizophrenia. In this work, surface plasmon resonance has been employed to screen a fragment library, from which two fragments, F6037-0164 and F0037-7280 were pursued (IC50 of 524.5 μM and 115.2 μM, respectively). Another strategy was to consider estrogen compounds as schizophrenia is a sexually dimorphic condition, in which female patients have reduced estrogen levels. Enzyme inhibitory assays displayed estradiol disulfate as a strong inhibitor of KAT-I and KAT-II (IC50: 291.5 μM and 26.3 μM, respectively), with estradiol, estradiol 3-sulfate and estrone sulfate inhibiting weakly. Molecular modelling suggests that the 17-sulfate moiety in estradiol disulfate improves its potency by 10-100 fold compared to estradiol. This 17-sulfate moiety was mimicked on existing KAT-II inhibitor scaffolds to develop two novel inhibitors, JN-01 and JN-02, with improved potencies (IC50: 73.8 μM and 112.8 μM, respectively). Co-crystallisation studies resulted in the determination of a human KAT-II crystal structure (PDB ID: 6D0A) with 1.47 Å resolution, the highest resolution structure provided for KAT-II, with the least structural inconsistencies.