"Steroidogenesis inhibitor" from_date:2012

Osilodrostat Is a Potential Novel Steroidogenesis Inhibitor for the Treatment of Cushing Syndrome: An In Vitro Study. Metyrapone and ketoconazole, frequently used steroidogenesis inhibitors for treatment of Cushing syndrome, can be associated with side effects and limited efficacy. Osilodrostat is a CYP11B1 and CYP11B2 inhibitor, with unknown effects on other steroidogenic enzymes. To compare with metyrapone. All steroidogenesis inhibitors showed large variability in sensitivity between primary adrenocortical cultures. Osilodrostat might inhibit CYP11B1 and CYP11B2, in some conditions to a lesser extent CYP17A1 activity, and a proximal step in the steroidogenesis. Osilodrostat is a promising treatment option for Cushing syndrome, and in vivo differences with metyrapone are potentially driven

The anti-Müllerian hormone (AMH) acts as a gatekeeper of ovarian steroidogenesis inhibiting the granulosa cell response to both FSH and LH Anti Müllerian Hormone (AMH) has a negative and inhibitory role in many functions of human granulosa-lutein cells (hGCs) including notoriously the reduction of the aromatase CYP19A1 expression induced by follicle-stimulating hormone (FSH). No data have been

. Surgery may not always be possible and does not always lead to remission. * Medical therapies can be used for mild hypercortisolism or as an adjunct for severe hypercortisolism while other treatment is awaited; if persistent or recurrent hypercortisolism occurs after surgery; or if surgery is declined or not feasible. Medications used to manage hypercortisolism include steroidogenesis inhibitors (which

TrialsTreatment Options for Adrenocorticotropic Hormone (ACTH)-Producing Pituitary TumorsTreatment options for ACTH-producing pituitary tumors include the following:Surgery (usually a transsphenoidal approach).[1-3]Surgery plus radiation therapy.[1,2,4]Radiation therapy.[1,2,4]Steroidogenesis inhibitors, including mitotane, metyrapone, ketoconazole, and aminoglutethimide.[1,2,5]Stereotactic radiation surgery ] Steroidogenesis inhibitors, including mitotane, metyrapone, ketoconazole, and aminoglutethimide are used. Ketoconazole is the best tolerated of these agents and is effective as monotherapy in about 70% of patients.[5]If untreated, patients frequently succumb to cardiovascular disease or infection.Current Clinical TrialsUse our advanced clinical trial search to find NCI-supported cancer clinical trials

or whole-body imaging can help identify tumor sources of hypercortisolism. Management of Cushing syndrome begins with surgery to remove the source of excess endogenous cortisol production followed by medication that includes adrenal steroidogenesis inhibitors, pituitary-targeted drugs, or glucocorticoid receptor blockers. For patients not responsive to surgery and medication, radiation therapy

and limitations of steroidogenesis inhibitors, pituitary-directed drugs, glucocorticoid receptor antagonists, and experimental drugs targeting novel molecular pathways that have been implicated in the pathogenesis of hypercortisolism. Despite advancements, significant unmet needs persist, underscoring the importance of personalized treatment approaches and the development of targeted therapies. Ongoing

steroidogenesis inhibitors but 10/13 were not controlled. In these patients, osilodrostat monotherapy, used in second line, induced a significantly decreased of 24h-UFC (from 2.6xULN [1.1-144] to 0.22xULN [0.12-0.66]; p < 0.01). Nine additional patients received osilodrostat in combination with another anticortisolic drug decreasing 24h-UFC from 11.8xULN (0.3-247) to 0.43xULN (0.33-2.4) (p < 0.01).In parallel

’s ketoconazole was reported to have steroidogenesis inhibitor effects linked to a broad inhibition of cytochrome P450 enzymes. The applicant refers back to more than 400 publications dating from mid 1980’s. The CHMP confirmed that the requirement of not less than one decade of medical use in in the applied indication in the EU is fulfilled. The literature provided by the applicant showed

steroidogenesis inhibitor of 11β-hydroxylase (CYP11β1) that induced remission of hypercortisolism in 86% of patients with refractory CD in the randomized placebo-controlled trial LINC-3 (NCT02180217). A 40-year-old woman with persistent CD following transsphenoidal surgery was treated with osilodrostat in the LINC-3 trial and was followed with regular hormonal assessments and imaging of residual corticotroph and increased proliferative index (Ki-67 ≥ 8%) resulted in current remission but will require close follow-up. This case highlights the importance of monitoring ACTH and corticotroph tumor size in patients with persistent CD, either under effective treatment with steroidogenesis inhibitors or after bilateral adrenalectomy.

-administration assay in zebrafish. This paradigm showed that finasteride, a steroidogenesis inhibitor approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia, reduced self-administration of multiple opioids without affecting locomotion or feeding behavior. These findings were confirmed in rats; furthermore, finasteride reduced the physical signs associated with opioid withdrawal

We recommend measuring serum cortisol or urine free cortisol (UFC) off-medication at 6- to 12-month intervals to assess the effect of RT and also if patients develop new adrenal insufficiency symptoms while on stable medical therapy. (1|⊕⊕⊕⚪)6.4 Medical treatment * 6.4 We recommend steroidogenesis inhibitors under the following conditions: as second-line treatment after TSS in patients with CD

and will be awaiting its salutary effects to occur. Available treatment options include steroidogenesis inhibitors, centrally acting agents and glucocorticoid receptor antagonists. Several novel agents are in clinical trials and may eventually constitute additional treatment options for this serious condition.

Cabergoline in Severe Ectopic or Occult Cushing's Syndrome. Cabergoline has been shown to have some effect in the treatment of moderate Cushing's disease, but its effectiveness in Cushing's syndrome of ectopic or occult origin remains to be investigated. In this case series, cabergoline was used in combination with steroidogenesis inhibitors in nine patients with severe Cushing's syndrome of ectopic or occult origin. Cabergoline's effectiveness enabled rapid withdrawal of the steroidogenesis inhibitors and long-term control of the hypercortisolism in three of the cases. In the literature, we found only 11 cases of ectopic or occult Cushing's syndrome treated with dopamine receptor agonists, alone or in combination. Yet of these 11 cases, 10 responded. Although limited, the existing

of 35 patients with AR positive tumors concurrently expressed enzymes for adrenal androgen utilization and nine expressed enzymes for steroidogenesis (HSD3B1, CYP17A, AKR1C3, and HSD17B3). Mice are appropriate for evaluating adrenal impact of steroidogenesis inhibitors. A subset of ADX-resistant CRPC tumors demonstrate androgen synthesis. Tumor growth and androgens were suppressed more strongly

may to be superior to other steroidogenesis inhibitors due to its low toxicity. For future in vivo studies, dogs with endogenous CS may provide a useful animal model.

Spontaneous adrenocorticotropic hormone (ACTH) normalisation due to tumour regression induced by metyrapone in a patient with ectopic ACTH syndrome: case report and literature review. Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is caused by tumours releasing ACTH. Ectopic ACTH-producing tumour regression is rarely induced using steroidogenesis inhibitors. We presented a case of EAS in which ACTH production by a lung tumour was reduced by metyrapone (MTP) and also reviewed previous cases of ectopic ACTH production suppressed via steroidogenesis inhibition. A 71-year-old female with general fatigue, central obesity and impaired glucose tolerance was diagnosed with Cushing's syndrome due to elevated ACTH (192.9 pg/mL; normal range, 7.2-63.3 pg/mL), cortisol (73.1 μg/dL; 6.4-21.0 μg/dL

Effects of Ketoconazole on the Pharmacokinetics of Mifepristone, a Competitive Glucocorticoid Receptor Antagonist, in Healthy Men Mifepristone, a competitive glucocorticoid receptor antagonist approved for Cushing syndrome, and ketoconazole, an antifungal and steroidogenesis inhibitor, are both inhibitors of and substrates for cytochrome P450 (CYP3A4). This study evaluated the pharmacokinetic

Drug Interaction Potential of Osilodrostat (LCI699) Based on Its Effect on the Pharmacokinetics of Probe Drugs of Cytochrome P450 Enzymes in Healthy Adults Osilodrostat (LCI699) is an adrenal steroidogenesis inhibitor currently in late-phase clinical development as a potential treatment for Cushing's disease. This study evaluated the inhibitory effect of osilodrostat on the pharmacokinetics

in sites of distant metastases, with minimal uptake in the sellar region. 1.2.2. Osilodrostat Osilodrostat is a recently developed steroidogenesis inhibitor that acts mainly on both adrenal 11-beta hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) (17). It is administered orally, twice daily and its efficacy and tolerability have been established through a clinical trial programme currently

Bilateral adrenalectomy in the 21st century: when to use it for hypercortisolism? Therapeutic options available for the treatment of Cushing's syndrome (CS) have expanded over the last 5 years. For instance, the efficient management of severe hypercortisolism using a combination of fast-acting steroidogenesis inhibitors has been reported. Recent publications on the long-term efficacy of drugs