Delving into the Latest Updates on Nevanimibe with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Atr-101 free base, Nevanimibe (USAN), Nevanimibe Hydrochloride

+ [4]

Target

SOAT1

Mechanism

SOAT1 inhibitors(Acyl coenzyme A:cholesterol acyltransferase 1 inhibitors)

Therapeutic Areas

Congenital DisordersEndocrinology and Metabolic DiseaseUrogenital Diseases+ [2]

Active Indication-

Inactive Indication

Acetyl-Coa Carboxylase DeficiencyAdrenal Hyperplasia, CongenitalAdrenocortical Carcinoma+ [1]

Originator Organization

Millendo Therapeutics, Inc.

Active Organization-

Inactive Organization

Millendo Therapeutics US, Inc.

Millendo Therapeutics, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

RegulationOrphan Drug (US)

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Structure/Sequence

Molecular FormulaC27H39N3O

InChIKeyPKKNCEXEVUFFFI-UHFFFAOYSA-N

CAS Registry133825-80-6

View All Structures (2)

This is a multicenter, intra-subject dose-titration open-label study of nevanimibe hydrochloride (HCl) for the treatment of classic congenital adrenal hyperplasia (CAH). Following a Screening Period of approximately 2-14 weeks, eligible subjects will enter a Baseline Period of approximately 2-8 weeks and then a 16-week Treatment Period. It is anticipated that the overall duration of the study per subject will range from 24-42 weeks.

Start Date11 Jul 2018

Sponsor / Collaborator

Millendo Therapeutics US, Inc.

EUCTR2016-002240-17-GB

/ Not yet recruitingPhase 2

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ATR-101 for the Treatment of Cushing’s Syndrome

Start Date16 May 2017

Sponsor / Collaborator

Millendo Therapeutics, Inc.

100 Clinical Results associated with Nevanimibe

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100 Translational Medicine associated with Nevanimibe

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100 Patents (Medical) associated with Nevanimibe

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21

Literatures (Medical) associated with Nevanimibe

01 Dec 2024·Molecular and Cellular Endocrinology

The impact of acyl-CoA:cholesterol transferase (ACAT) inhibitors on biophysical membrane properties depends on membrane lipid composition

Article

Author: Scheidt, Holger A. ; To, Huong ; Scheidt, Holger A ; Akkerman, Vibeke ; Müller, Peter ; Lauritsen, Line ; Bashawat, Mohammad ; Luck, Meike ; Kroiss, Matthias ; Wüstner, Daniel ; Reinholdt, Peter ; Kongsted, Jacob

Acyl-coenzyme A: cholesterol acyltransferases are enzymes which are involved in the homeostasis of cholesterol. Impaired enzyme activity is associated with the occurrence of various diseases like Alzheimer's disease, atherosclerosis, and cancers. At present, mitotane is the only inhibitor of this class of enzymes in clinical use for the treatment of adrenocortical carcinoma but associated with common and severe adverse effects. The therapeutic effect of mitotane depends on its interaction with cellular membranes. The search for less toxic but equally effective compounds is hampered by an incomplete understanding of these biophysical properties. In the present study, the interaction of the three ACAT inhibitors nevanimibe, Sandoz 58-035, and AZD 3988 with membranes has been investigated using lipid model membranes in conjunction with biophysical experimental (NMR, ESR, fluorescence) and theoretical (MD simulations) approaches. The data show, that the drugs (i) incorporate into lipid membranes, (ii) differently influence the structure of lipid membranes; (iii) affect membrane structure depending on the lipid composition; and (iv) do not cause hemolysis of red blood cells. The results are discussed with regard to the use of the drugs, in particular to better understand their efficacy and possible side effects.

01 Dec 2021·StructureQ2 · BIOLOGY

Molecular structures of human ACAT2 disclose mechanism for selective inhibition

Q2 · BIOLOGY

Article

Author: Liu, Yang ; Li, Xiaochun ; Long, Tao

Endoplasmic reticulum-localized acyl-CoA:cholesterol acyltransferases (ACAT), including ACAT1 and ACAT2, convert cholesterol to cholesteryl esters that become incorporated into lipoproteins or stored in cytosolic lipid droplets. Selective inhibition of ACAT2 has been shown to considerably attenuate hypercholesterolemia and atherosclerosis in mice. Here, we report cryogenic electron microscopy structures of human ACAT2 bound to its specific inhibitor pyripyropene A or the general ACAT inhibitor nevanimibe. Structural analysis reveals that ACAT2 has a topology in membranes similar to that of ACAT1. A catalytic core with an entry site occupied by a cholesterol molecule and another site for allosteric activation of ACAT2 is observed in these structures. Enzymatic assays show that mutations within sites of cholesterol entry or allosteric activation attenuate ACAT2 activity in vitro. Together, these results reveal mechanisms for ACAT2-mediated esterification of cholesterol, providing a blueprint to design new ACAT2 inhibitors for use in the prevention of cardiovascular disease.

01 Jun 2021·Current Opinion in Endocrinology, Diabetes & ObesityQ3 · MEDICINE

Clinical outcomes in 21-hydroxylase deficiency

Q3 · MEDICINE

Review

Author: Falhammar, Henrik ; Nordenström, Anna ; Lajic, Svetlana

Purpose of reviewThe introduction of synthetic glucocorticoids 70 years ago made survival possible in classic 21-hydroxylase deficiency (21OHD). The currently used glucocorticoid therapy may lead to unphysiological dosing with negative consequencies on health in addition to the problems that may arise due to androgen over-exposure.Recent findingsFertility in females with 21OHD seemed to be impaired, especially in the salt-wasting (SW) phenotype but when pregnancies did occur there was a higher risk for gestational diabetes and cesearean section. Increased fat mass, body mass index, insulin resistance and frequency of autoimmune disorders as well as impaired echocardiographic parameters and lower bone mineral density were found in 21OHD compared to controls. Negative effects on cognitive functions have been identified. Adrenal tumors, especially myelolipomas, were prevalent. Increased knowledge on steroid metabolism in 21OHD and urine steroid profiling may improve assessment of treatment efficacy. Nevanimibe, abiraterone acetate and anastrozole may have a place in the future management of 21OHD. Long-acting glucocorticoids may be a less favorable, especially dexamethasone.SummaryThe various clinical outcomes need regular monitoring. Negative consequencies are to large extent the result of the unphysiological glucocorticoid replacement. Modern management with improved follow-up and future addition of new drugs may improve outcomes.

100 Deals associated with Nevanimibe

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External Link

KEGG	Wiki	ATC	Drug Bank
D11300	-	-	DB16254

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Endogenous Cushing Syndrome	Phase 2	US	Millendo Therapeutics US, Inc.	13 Apr 2017
Endogenous Cushing Syndrome	Phase 2	GB	Millendo Therapeutics US, Inc.	13 Apr 2017
Adrenal Hyperplasia, Congenital	Phase 2	US	Millendo Therapeutics, Inc.	18 May 2016
Adrenal Hyperplasia, Congenital	Phase 2	US	Millendo Therapeutics, Inc.	18 May 2016
Acetyl-Coa Carboxylase Deficiency	Phase 2	US	Millendo Therapeutics, Inc.	13 Aug 2013
Acetyl-Coa Carboxylase Deficiency	Phase 2	DE	Millendo Therapeutics, Inc.	13 Aug 2013
Adrenocortical Carcinoma	Phase 2	DE	Millendo Therapeutics, Inc.	13 Aug 2013
Adrenocortical Carcinoma	Phase 2	US	Millendo Therapeutics, Inc.	13 Aug 2013

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03053271 (CTgov)	Phase 2	Endogenous Cushing Syndrome	4	ATR-101 (Nevanimibe HCl)	ptioehmbov(qelfkeegnu) = mmswypeycx jufnuagkjf (revqvtbtqt, qcwyqobghu - pahzcspdzq) View more	-	02 Mar 2021
NCT02804178 (CTgov)	Phase 2	Adrenal Hyperplasia, Congenital	10	ATR-101	bwbzcymkwp(rofoviafpv) = lhegftfcab ckhzypsxmo (snjbqkvhwy, mscablfkrb - zqssxsigdx) View more	-	17 Feb 2021
NCT02804178 (Pubmed \| J Clin Endocrinol Metab) Manual	Phase 2	Adrenal Hyperplasia, Congenital	10	Placebo+Nevanimibe	(vtaiorspoh) = nvulodgwvr auqwekcgrt (ggpxfpdlvy ) View more	Positive	01 Aug 2020