Delving into the Latest Updates on Metyrapone with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Cormeto, Metirapona, Metycor

+ [7]

Target

CYP11B1

Mechanism

CYP11B1 inhibitors(Steroid 11-beta-hydroxylase inhibitors)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic DiseaseOther Diseases

Active Indication

Adrenal InsufficiencyCushing SyndromePituitary ACTH Hypersecretion

Inactive Indication

Endogenous Cushing Syndrome

Originator Organization

Novartis SA

Active Organization

HRA Pharma Development SARL

Novartis AGHRA Pharma Rare Diseases SAS

+ [2]

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

US (04 Dec 1961),

Pituitary ACTH Hypersecretion

RegulationOrphan Drug (US)

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Structure

Molecular FormulaC14H14N2O

InChIKeyFJLBFSROUSIWMA-UHFFFAOYSA-N

CAS Registry54-36-4

In a randomized, cross-over study, 20 healthy volunteers will receive a block and replace therapy that mimics physiological GC rhythm (metyrapone plus hydrocortisone) or placebo. Participants will undergo two identical fasting periods with each treatment. With the block and replace therapy, fasting-induced GC peak will be suppressed. Metabolic and autonomic parameters will be compared to reveal whether GCs mediate the physiological adaptions to caloric restriction.
Understanding acute effects of GCs upon caloric restriction is critical, since repetitive disruptions of GC secretion may become harmful in chronic conditions.

Start Date15 May 2023

Sponsor / Collaborator-

NCT05255900 / RecruitingNot ApplicableIIT

Metabolic, Pressor and Neuropsychological Effects of Metyrapone Treatment in Patients With Hypercortisolism

The aims of the present study are to evaluate in patients with mild hypercortisolism the effect of metyrapone treatment on glycometabolic control, blood pressure, thrombotic risk parameters, lipid profile, bone turnover markers, mental health and cortisol circadian rhythm.

Start Date28 Apr 2022

Sponsor / Collaborator

Istituto Auxologico Italiano

[+1]

100 Clinical Results associated with Metyrapone

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100 Translational Medicine associated with Metyrapone

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100 Patents (Medical) associated with Metyrapone

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3,541

Literatures (Medical) associated with Metyrapone

08 Jan 2024·JCEM case reports

Prolonged Hypokalemia Following Metyrapone Treatment for Primary Bilateral Macronodular Adrenal Cortical Disease

Author: Kakutani-Hatayama, Miki ; Kidawara, Yonekazu ; Koyama, Hidenori ; Fukuoka, Hidenori

Abstract:

Surgical treatment is generally the standard therapeutic regimen used for primary bilateral macronodular adrenal cortical disease (PBMACD). However, in cases for which surgery is difficult or in which there is mild cortisol hypersecretion, metyrapone treatment can be selected. Although hypokalemia has been occasionally noted following metyrapone administration for Cushing syndrome associated with an adrenal adenoma, all such cases have been reported to be transient. Hypokalemia induced by metyrapone treatment is thought to occur due to excessive suppression of cortisol secretion, resulting in overproduction of adrenocorticotropic hormone from the pituitary gland, ultimately leading to excessive production of 11-deoxycorticosterone (DOC) in the adrenal cortex. A 52-year-old man diagnosed with PBMACD and started on metyrapone treatment subsequently presented with persistent hypokalemia. Interestingly, following initiation of metyrapone, blood test findings indicated marginal changes in serum cortisol, adrenocorticotropic hormone, and dehydroepiandrosterone sulfate levels, even when DOC levels were already markedly elevated. In addition to the effects of metyrapone, the present findings suggest a unique DOC synthesis regulatory mechanism involved in the pathogenesis of PBMACD.

01 Feb 2024·Data in brief

Transcriptomic data of human adrenocortical NCI-H295R cells treated with cortisol biosynthesis inhibitors

Article

Author: Jung, Jong-Wha ; Chung, Sooyoung ; Son, Gi Hoon ; Kim, Soo Hyun ; Kim, Hyun Jung

Adrenal corticosteroid biosynthesis dysregulation can give rise to various pathological conditions, such as Cushing's syndrome, a disorder characterized by the sustained and excessive production of cortisol. Despite the development of several classes of steroidogenesis inhibitors to treat human diseases associated with cortisol overproduction, their use is limited by insufficient efficacy, adverse effects, and/or tolerability. Recently, we identified a series of benzimidazolylurea derivatives, including the representative compound CJ28, as novel cortisol biosynthesis inhibitors [1]. They significantly inhibited both basal and stimulated production of cortisol in NCI-H295R cells, a human adrenocarcinoma cell line. The inhibitory effects were attributed to both attenuated steroidogenesis and de novo cholesterol biosynthesis. Here, we provide transcriptomic (RNA-seq) data from adrenal cell cultures in response to treatment with either CJ28 or metyrapone (MET), an inhibitor of 11β-hydroxylase). Total RNA was extracted from the cells treated with vehicle (0.1% DMSO), CJ28 (30 µM), or MET (30 µM) for 24 h. Primary sequence data were acquired using paired-end sequencing on an Illumina NovaSeq 6000 platform. The raw RNA-seq data have been deposited in the Gene Expression Omnibus (GEO) database (GSE236435). This dataset is a useful resource for providing valuable information on the gene expression networks underlying adrenocortical steroidogenesis.

01 Feb 2024·Comparative biochemistry and physiology. Part A, Molecular & integrative physiology

Cortisol enhances aerobic metabolism and locomotor performance during the transition to land in an amphibious fish

Article

Author: Wright, Patricia A ; Rossi, Giulia S ; Bernier, Nicholas J ; Young, Sarah J

Amphibious fishes on land encounter higher oxygen (O₂) availability and novel energetic demands, which impacts metabolism. Previous work on the amphibious mangrove killifish (Kryptolebias marmoratus) has shown that cortisol becomes elevated in response to air exposure, suggesting a possible role in regulating metabolism as fish move into terrestrial environments. We tested the hypothesis that cortisol is the mechanism by which oxidative processes are upregulated during the transition to land in amphibious fishes. We used two groups of fish, treated fish (+metyrapone, a cortisol synthesis inhibitor) and control (-metyrapone), to determine the impact of cortisol during air exposure (0 and 1 h, 7 days) on O₂ consumption, terrestrial locomotion, the phenotype of red skeletal muscle, and muscle lipid concentration. Metyrapone-treated fish had an attenuated elevation in O₂ consumption rate during the water to air transition and an immediate reduction in terrestrial exercise performance relative to control fish. In contrast, we found no short- (0 h) or long-term (7 days) differences between treatments in the oxidative phenotype of red muscles, nor in muscle lipid concentrations. Our results suggest that cortisol stimulates the necessary increase in aerobic metabolism needed to fuel the physiological changes that amphibious fishes undergo during the acclimation to air, although further studies are required to determine specific mechanisms of cortisol regulation.

2

News (Medical) associated with Metyrapone

26 Apr 2024

·firstwordpharma.com

Perrigo to divest rare diseases unit to Spain's Esteve for €275 million

Perrigo is offloading its HRA Pharma Rare Diseases business to Barcelona-based pharmaceutical company Esteve Healthcare for a total of up to €275 million ($294 million) and plans to use the proceeds to help pay down its debt.The transaction, which includes €190 million in cash upfront plus up to €85 million in potential earnouts if certain sales targets are reached, is expected to close in the third quarter.The unit's three-product portfolio includes the Cushing's syndrome treatments Metopirone (metyrapone) and ketoconazole, as well as Lysodren (mitotane), which is prescribed to treat adrenal cortical carcinoma. Staffan Schüberg, chief executive at Esteve, said the deal is "another step towards the company's vision of being an international and specialist pharma company."Meanwhile, Perrigo CEO Patrick Lockwood-Taylor said the divestment "further supports our position as a leading fast-moving consumer goods company," adding that the upfront cash proceeds would allow the company "to reduce net leverage to below 4.0x by the end of 2024."

AcquisitionDrug Approval

09 May 2023

·www.pharmaceutical-technology.com

FibroGen and Fortis sign exclusive licence deal for mCRPC drug candidate

FOR46 is being developed as a potential treatment for metastatic castration-resistant prostate cancer. Credit: Nephron/commons.wikimedia.org FibroGen has signed an exclusive licence agreement with Fortis Therapeutics for the FOR46 antibody-drug conjugate (ADC) that targets a new epitope on CD46, a protein-coding gene. FOR46 is currently being investigated in a Phase I trial as a potential treatment for metastatic castration-resistant prostate cancer (mCRPC). Recommended Reports Reports LOA and PTSR Model - (Metyrapone + Oxazepam) in Substance (Drug) Abuse GlobalData Reports LOA and PTSR Model - Esmethadone Hydrochloride in Substance (Drug) Abuse GlobalData View all The trial is also studying the capability of FOR46 for use in other CD46-expressing cancers. The new deal, which does not include any initial consideration, will see FibroGen conducting and financing new research, development and production of FOR46 and PET46. Throughout the deal’s four-year evaluation period, FibroGen has an option to buy Fortis Therapeutics for $80m. Fortis can also receive up to $200m in total on the basis of multiple regulatory approvals. Under the clinical development strategy, FibroGen will continue the work of Fortis Therapeutics to develop a PET-based biomarker using a radiolabeled version of the targeting antibody (PET46) for selecting patients. FibroGen CEO Enrique Conterno stated: “The agreement with Fortis Therapeutics bolsters FibroGen’s clinical pipeline in a capital-efficient manner, providing a product candidate with the potential to address a significant unmet medical need in oncology. “FOR46 is a natural fit with our research and development capabilities and expertise. “The flexibility of the agreement gives us the opportunity to clinically develop FOR46, and ultimately acquire it as a Phase III-ready asset, potentially delivering a therapy that may transform the treatment of patients with mCRPC and other CD46-expressing cancers.” In early May 2023, FibroGen announced that it would receive a $150m non-dilutive term loan facility from funds managed by Morgan Stanley Tactical Value (MSTV) to accelerate the commercialisation of pamrevlumab.

Phase 1License out/inADCAcquisition

100 Deals associated with Metyrapone

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External Link

KEGG	Wiki	ATC	Drug Bank
D00410	Metyrapone	V04CD01	DB01011

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Adrenal Insufficiency	-	Novartis AG	30 May 2014
Cushing Syndrome	AU	CHIESI Farmaceutici SpA	02 Aug 1991
Pituitary ACTH Hypersecretion	US	HRA Pharma Rare Diseases SAS	04 Dec 1961

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Endogenous Cushing Syndrome	Phase 3	BE	HRA Pharma Development SARL	01 Apr 2015
Endogenous Cushing Syndrome	Phase 3	DE	HRA Pharma Development SARL	01 Apr 2015
Endogenous Cushing Syndrome	Phase 3	HU	HRA Pharma Development SARL	01 Apr 2015
Endogenous Cushing Syndrome	Phase 3	IT	HRA Pharma Development SARL	01 Apr 2015
Endogenous Cushing Syndrome	Phase 3	PL	HRA Pharma Development SARL	01 Apr 2015
Endogenous Cushing Syndrome	Phase 3	RO	HRA Pharma Development SARL	01 Apr 2015
Endogenous Cushing Syndrome	Phase 3	ES	HRA Pharma Development SARL	01 Apr 2015
Endogenous Cushing Syndrome	Phase 3	TR	HRA Pharma Development SARL	01 Apr 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESPE2016	Not Applicable	Cushing Syndrome	-	Metyrapone	ophtxinkmq(impvxtrvno) = xjdjfwdlve gxhhjrzynj (lcetubefqf )	-	10 Sep 2016
Pubmed	Not Applicable	Cushing Syndrome	195	Metyrapone	othihecvqo(xliryvezmz) = zfvoywtgbh irrjulvqau (zevebbzghw ) View more	Positive	01 Nov 2015