nilutamide

We screened 6 nitro-containing drugs (flunitrazepam, clonazepam, nimesulide, nilutamide, flutamide, and chloramphenicol) as substrates against recombinant human AKR1C1, AKR1C2, AKR1C3, and AKR1C4, using discontinuous enzymatic assays. We conclude that both AKR1C3 and AKR1C2 may have an important role in flunitrazepam drug response. SIGNIFICANCE STATEMENT: Aldo-keto reductase (AKR)1C3 reduces flunitrazepam to 7-amino-flunitrazepam through the formation of reactive nitroso and hydroxylamino intermediates, and by inhibiting AKR1C2, flunitrazepam may reduce the formation of the neuroactive steroid allopregnanolone.

P2/3, N=464, Recruiting, VA Office of Research and Development | Trial completion date: Dec 2025 --> Mar 2029 | Trial primary completion date: Jul 2025 --> Mar 2026

P2, N=310, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2025 --> Feb 2027 | Trial primary completion date: Feb 2025 --> Feb 2027

There was no statistical distance in PSA, caspase3, and caspase9 expressions among the three groups (P > 0.05). In vitro, lathyrol and nilutamide exert notable anticancer effects by effectively suppressing the proliferation, migration, and invasion of 786-O cells while also inducing apoptosis.

P2/3, N=612, Active, not recruiting, NRG Oncology | N=175 --> 612 | Trial completion date: May 2031 --> May 2026

Amongst the library of compounds, Adapalene exhibited the least binding energy of (-10.2 kCal/mol) in comparison to that of the chosen reference compound, Nilutamide (-8.6 kCal/mol). However, the overall effect of Adapalene was significantly lower in the case of MDA-MB-231 cell lines, which could be attributed to its inherent nature of the absence of hormone receptors. Conclusively, Adapalene possesses greater therapeutic efficacy in comparison to the control drug, thereby hinting towards the potential use of Adapalene in the treatment of AR-positive breast cancer.

Concerning OS, ADT + abiraterone, ADT + abiraterone + docetaxel, ADT + apalutamide, ADT + bicalutamide, ADT + darolutamide + docetaxel, ADT + enzalutamide, ADT + orteronel, and ADT + rezvilutamide were more effective than the standard of care (SOC). Comparing PFS, most treatments were more effective than SOC, excluding ADT + bicalutamide, nilutamide, flutamide, ADT + bicalutamide + palbociclib, and ADT + nilutamide...Novel oral chemotherapeutic agent combination therapies must replace current ADT monotherapy and ADT + docetaxel SOC. Even so, ADT + docetaxel with ARTA triplet therapy still is not the best mHSPC treatment and requires further study.

Early efforts to augment ADT by adding adrenal-targeting agents (aminoglutethimide, ketoconazole) or AR antagonists (flutamide, bicalutamide, nilutamide, cyproterone) failed to achieve overall survival (OS) benefits, although they did exhibit some evidence of limited clinical activity...Specifically, the CYP17 inhibitor abiraterone acetate and the 2nd generation AR antagonists (enzalutamide, apalutamide and darolutamide) achieved OS benefits for PC patients, confirmed the importance of reactivated AR signaling in castration-resistant PC and validated important concepts that had been proposed in the field several decades ago but had remained so far unproven, including adrenal-targeted therapy and combined androgen blockade...Now the question is raised whether we have accomplished the maximum AR axis inhibition possible or there is still room for improvement. This review, marking the 80-year anniversary of ADT and 10-year anniversary of successful ARSIs, examines their current clinical use and discusses future directions, in particular combination regimens, to maximize their efficacy, delay emergence of resistance and improve patient outcomes.

The therapeutic action of nitroaromatic antiandrogens nilutamide and flutamide may be complicated by their cytotoxicity, whose mechanisms are still incomprehensively understood. Using murine hepatoma MH22a cells, the obtained cytotoxicity vs. E correlation based on the data of model nitroaromatic compounds shows that redox cycling and oxidative stress could be the main factor of cytotoxicity of nitroaromatic antiandrogens. Other minor cytotoxicity factors could be their redox metabolism involving NAD(P)H:quinone oxidoreductase (NQO1) and cytochromes P-450.