OPK 88004 / OPKO Health, Eli Lilly - LARVOL DELTA

Polypharmacological profiling across protein target families and cellular pathways using the multiplexed cell-based assay platform safetyProfiler reveals efficacy, potency and side effects of drugs. (PubMed, Biomed Pharmacother) - "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."

Adverse events • Journal • Breast Cancer • Genito-urinary Cancer • Hormone Receptor Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • DRD2 • EGFR • ERBB4 • HTR2A

Selective Androgen Receptor Modulators (SARMs) Effects on Physical Performance: A Systematic Review of Randomized Control Trials. (PubMed, Clin Endocrinol (Oxf)) - "SARMs have a positive effect on physical performance and body composition and are associated with moderate rates of mild to moderate adverse effects (AEs) and a low rate of severe AEs."

Journal • Review • Cachexia • Oncology • Sarcopenia

Metabolic study of selective androgen receptor modulator LY2452473 in thoroughbred horses for doping control. (PubMed, Rapid Commun Mass Spectrom) - "Data obtained will aid in identifying LY2452473 and related substances faster, furthermore, the results will assist in checking for the illegal use of these substances in competitive sports."

Journal

Effect of Selective Androgen Receptor Modulator on Cholesterol Efflux Capacity, Size, and Subspecies of HDL Particles. (PubMed, J Endocr Soc) - "To determine the effects of an oral SARM (OPK-88004) on cholesterol efflux capacity, HDL particle number and size, apolipoprotein particle number and size and HDL subspecies...SARM-induced increase in HTGL could contribute to HDL-C suppression. These data do not support the simplistic notion that SARM-associated suppression of HDL-C is necessarily proatherogenic; randomized trials are needed to determine SARM's effects on cardiovascular events."

Journal • Cardiovascular • Coronary Artery Disease • Genito-urinary Cancer • Heart Failure • Oncology • Prostate Cancer • Solid Tumor • A2M • APOA1 • APOB • APOE

A Selective Androgen Receptor Modulator (OPK-88004) in Prostate Cancer Survivors: A Randomized Trial. (PubMed, J Clin Endocrinol Metab) - "Administration of OPK-8804 was safe and not associated with PSA recurrence in androgen-deficient men who had undergone radical prostatectomy for organ-confined prostate cancer. OPK-88004 increased lean body mass and decreased fat mass, but did not improve sexual symptoms or physical performance."

Clinical • Journal • Fatigue • Genito-urinary Cancer • Hematological Disorders • Oncology • Prostate Cancer • Sexual Disorders • Solid Tumor

Simultaneous detection of different chemical classes of selective androgen receptor modulators in urine by liquid chromatography-mass spectrometry-based techniques. (PubMed, J Pharm Biomed Anal) - "In detail, 19 target compounds belonging to 9 different chemical classes were considered: arylpropionamide (i.e., andarine (S4), ostarine (S22), S1, S6, S9 and S23), diarylhydantoin (i.e., GLPG0492), indole (i.e., LY2452473, GSK2881078), isoquinoline-carbonyle (i.e., PF-02620414), phenyl-oxadiazole (i.e., RAD140), pyrrolidinyl-benzonitrile (i.e., LGD4033), quinolinone (i.e., LGD2226, LGD3303), steroidal (i.e., Cl-4AS-1, MK0773 and TFM-4AS-1), and tropanol (i.e., AC-262536 and ACP105) derivatives. Urine samples containing andarine, ostarine, or LGD4033 were used to confirm the actual applicability of the selected analytical strategies. All target compounds (parent drugs and their main metabolites) were detected and correctly identified."

Journal

A Selective Androgen Receptor Modulator for Symptom Management in Prostate Cancer (clinicaltrials.gov) - P2; N=114; Completed; Sponsor: Dana-Farber Cancer Institute; Trial completion date: Nov 2019 ➔ Oct 2020; Trial primary completion date: Oct 2019 ➔ Oct 2020

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Development of a multi-residue high-throughput UHPLC-MS/MS method for routine monitoring of SARM compounds in equine and bovine blood. (PubMed, Drug Test Anal) - "The presented screening method validation was performed in line with current EU legislation for the inspection of livestock and produce of animal origin, with CCβ values determined at 0.5 ng mL (Ly2452473), 1 ng mL (AC-262536 and PF-06260414), 2 ng mL (bicalutamide, GLPG0492, LGD-2226, ostarine, S-1, S-6, and S-23) and 5 ng mL (andarine, BMS-564929, LGD-4033, RAD140, and S-9), respectively. Applicability of the developed assay was demonstrated through the analysis of blood samples from racehorses and cattle. The developed method presents a high-throughput cost-effective tool for routine screening for a range of SARM compounds in sport and livestock animals."

Journal

Effects and Safety of OPK-88004 Doses in Men With Signs and Symptoms of Benign Prostatic Hyperplasia (BPH) (clinicaltrials.gov) - P2; N=126; Not yet recruiting; Sponsor: Transition Therapeutics Ireland Limited

New P2 trial • Biosimilar

A Selective Androgen Receptor Modulator for Symptom Management in Prostate Cancer (clinicaltrials.gov) - P2; N=114; Completed; Sponsor: Dana-Farber Cancer Institute; Active, not recruiting ➔ Completed; Trial completion date: Nov 2022 ➔ Nov 2019

Trial completion • Trial completion date

A Selective Androgen Receptor Modulator for Symptom Management in Prostate Cancer (clinicaltrials.gov) - P2; N=114; Active, not recruiting; Sponsor: Dana-Farber Cancer Institute; Recruiting ➔ Active, not recruiting; Trial primary completion date: Jun 2019 ➔ Dec 2019

Enrollment closed • Trial primary completion date

Effects and Safety of OPK-88004 Doses in Men With Signs and Symptoms of Benign Prostatic Hyperplasia (BPH) (clinicaltrials.gov) - P2; N=114; Terminated; Sponsor: Transition Therapeutics Ireland Limited; Trial completion date: Dec 2018 ➔ May 2019; Recruiting ➔ Terminated; Trial primary completion date: Nov 2018 ➔ Apr 2019; study terminated by sponsor decision

Clinical • Trial completion date • Trial primary completion date • Trial termination

A Selective Androgen Receptor Modulator for Symptom Management in Prostate Cancer (clinicaltrials.gov) - P2; N=114; Recruiting; Sponsor: Dana-Farber Cancer Institute; N=450 ➔ 114; Trial primary completion date: Mar 2019 ➔ Jun 2019

Enrollment change • Trial primary completion date