For example, the neuroleptics clozapine, paliperidone, and risperidone potently inhibited primary targets DRD2 and HTR2A as well as cAMP and calcium pathways...Additionally, precise potency data for LY2452473, an androgen receptor antagonist, that completed a phase 2 clinical trial for prostate cancer, are presented. The non-selective kinase inhibitor staurosporine was observed to potently inactivate the two RTKs EGFR and ERBB4 as well as MAPK signaling, while eliciting stress-related cAMP responses. Our findings underscore the value of comprehensive profiling in elucidating the pharmacological properties of established and novel therapeutics, thereby facilitating the development of novel multi-target drugs with enhanced efficacy and selectivity.

Adding the CDK4/6 inhibitor palbociclib enhanced the antitumor activity of EP0062 or fulvestrant in ESR1-mutant models but not in HER2-enriched or PTEN-mutant PDX models...EP0062 triggers an E2F1 downmodulation which mediates a potent antiproliferative activity. For EP0062-resistant tumors that remain ER-driven, the addition of palbociclib displays a potent antitumor effect.

P2, N=150, Active, not recruiting, Veru Inc. | Recruiting --> Active, not recruiting

P2, N=150, Recruiting, Veru Inc. | N=90 --> 150

P2, N=90, Recruiting, Veru Inc. | Not yet recruiting --> Recruiting

P2, N=22, Terminated, GTx | Completed --> Terminated

P2, N=90, Not yet recruiting, Veru Inc.

P3, N=5, Terminated, Veru Inc. | N=186 --> 5

P2, N=18, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

Enobosarm has anti-tumour activity in patients with ER-positive, HER2-negative advanced breast cancer, showing that AR activation can result in clinical benefit, supporting further clinical investigation of selective AR activation strategies for the treatment of AR-positive, ER-positive, HER2-negative advanced breast cancer.

Furthermore, we established that the anti-carcinogenic activity of andarine is not mediated by the PI3K/AKT/mTOR signaling pathway, a crucial regulator of cell survival. Our findings suggest that andarine might be considered as a prospective drug for PC.

P1/2, N=128, Recruiting, Ellipses Pharma | Not yet recruiting --> Recruiting

P2, N=18, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jan 2023 --> Dec 2023

Since PI3K/AKT/mTOR signaling is frequently activated in HCC and contributes to its aggressiveness and poor prognosis, its negative regulation by the downregulation of critical components via S4 was a prominent finding. Further studies are necessary to investigate the S4 action mechanism and anti-tumorigenic capacity in in-vivo.

However, both a selective AR agonist (RAD140) and an AR inhibitor (enzalutamide, ENZ) have shown a therapeutic effect on ER+ breast cancer, so the potential for clinical application of AR-targeting therapy for ER+ breast cancer is still in dispute. In contrast, RAD140 activated AR signaling and suppressed AR-high tumor growth by deregulating ERα expression and blocking ERα function. Overall, analysis of the dynamic efficacies and outcomes of AR agonist and antagonist in the presence of different AR and ERα levels reveals regulators of response and supports the clinical investigation of ENZ in selected ER+ tumors with a low AR/ER ratio and AR agonists in tumors with a high AR/ER ratio.

P1/2, N=128, Not yet recruiting, Ellipses Pharma

Clinic follow-up will be at 2 and 4 weeks, then every 4 weeks until disease progression. Recruitment is scheduled to initiate in Q4 2022.