Castration-resistant prostate cancer (CRPC) is an unmet medical need. It originates from metastatic or relapsed prostate cancer that develops resistance to androgen deprivation therapy. The enzyme AKR1C3, which is upregulated in CRPC, is thought to be responsible for the development of resistance to androgen deprivation by increasing endogenous androgen levels within the prostate and promoting tumour progression. We have developed novel small molecule inhibitors of AKR1C3 that we will test in cellular models of CRPC to identify if the drug compounds effectively inhibit AKR1C3 and can prevent CRPC cell proliferation and androgen receptor signalling. In vivo models of CRPC will be used to investigate if AKR1C3 inhibition can prevent tumour growth either as single agent therapy or in combination with the standard therapy for CRPC. The compound(s) with the most promising antitumour efficacy will be selected for potential entry into clinical trials for the treatment of CRPC.