Evidence map›Paper›PMID 40437805›Full record

ArticleEndocrinology2025

Androgen Receptor PROTAC ARV-110 Ameliorates Metabolic Complications in a Mouse Model of Polycystic Ovary Syndrome.

Jelina Basnet, Samar Rezq, Alexandra M Huffman, Tolulope E Asala, Licy L Yanes Cardozo, Damian G Romero

Abstract read
In one paragraph

Article in Endocrinology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Ubiquitination and NOncology letters · 2026
    Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Jelina BasnetDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA.ORCID 0000-0001-5282-3859
Samar RezqDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA.ORCID 0000-0003-4421-0686
Alexandra M HuffmanDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA.ORCID 0000-0003-1223-1888
Tolulope E AsalaDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA.ORCID 0000-0001-5253-4328
Licy L Yanes CardozoDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA.ORCID 0000-0002-7295-1871
Damian G RomeroDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA.ORCID 0000-0002-7268-9690

Funding

STRUCTURAL VASCULAR ADAPTATION OF THE MICROCIRCULATIONP01HL051971 · NHLBI · UNIVERSITY OF MISSISSIPPI MEDICAL CENTER · PI HALL, JOHN E · 1993 to 2018
$39.4M
Investigator Development CoreP50MD017338 · NIMHD · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GUTIERREZ, ORLANDO M · 2021 to 2025
$27.7M
Role of obesity in preeclamptic pregnancy.P20GM121334 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI Ashley C. Johnson, Babbette LaMarca · 2017 to 2026
$26.4M
The role of leptin in autoimmune-associated hypertensionP20GM104357 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI TAYLOR, ERIN BASSFORD · 2013 to 2022
$23.4M
Supplement for Google cloud build-outR24GM137786 · NIGMS · UNIV OF ARKANSAS FOR MED SCIS · PI Alan Tackett · 2020 to 2026
$15.4M
Pilot Projects ProgramP30GM149404 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI DAVID E STEC · 2023 to 2026
$6.3M
Role of obesity in blood pressure regulation and insulin resistance in Polycystic Ovary SyndromeR01HL171494 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI LICY LORENA YANES CARDOZO · 2024 to 2026
$2.0M
Adrenal cell ATP1A1 mutations and mechanisms of aldosterone biosynthesisR01HL144847 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI GOMEZ-SANCHEZ, CELSO ENRIQUE · 2019 to 2022
$1.3M
Role of microRNA_21 in acetaminophen-induced acute liver failureR21DK113500 · NIDDK · UNIVERSITY OF MISSISSIPPI MED CTR · PI ROMERO, DAMIAN G. · 2017 to 2019
$580k
American Heart Association 24PRE1200831American Heart Association 903804American Heart Association P20GM104357American Heart Association P20GM121334American Heart Association R24GM137786NHLBI NIH HHS P01 HL051971NHLBI NIH HHS P01HL51971NHLBI NIH HHS R01 HL144847NHLBI NIH HHS R01 HL171494NIDDK NIH HHS R21 DK113500NIDDK NIH HHS R21DK113500NIGMS NIH HHS P20 GM104357NIGMS NIH HHS P20 GM121334NIGMS NIH HHS P20GM121334NIGMS NIH HHS P30 GM149404NIGMS NIH HHS P30GM149404NIGMS NIH HHS P50MD017338NIGMS NIH HHS R01HL144847NIGMS NIH HHS R01HL171494NIGMS NIH HHS R24 GM137786NIMHD NIH HHS P50 MD017338
6 · The paper itself

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. Hyperandrogenemia (HA) is a hallmark of PCOS and is positively associated with metabolic complications. Androgens exert their biological actions through the androgen receptor (AR), which regulates transcriptional activity. Antiandrogens are not recommended for managing metabolic complications in PCOS due to their hepatotoxicity, despite being a viable therapy to treat HA. We hypothesized that the novel AR Proteolysis Targeting Chimera (PROTAC) degrader ARV-110 would downregulate AR protein levels and actions to abolish or mitigate HA-mediated metabolic complications using a well-established HA mouse model of PCOS. Three-week-old female mice were implanted with dihydrotestosterone (DHT) or control pellets. Four weeks later, mice were treated with low- (ARV-110-L, 1 mg/kg.day) or high-dose (ARV-110-H, 10 mg/kg.day) ARV-110 for an additional 8 weeks. ARV-110 dose-dependently reduced AR protein levels in white adipose tissue (WAT), kidney, liver, and ovary. ARV-110 attenuated DHT-induced increases in body weight, fat mass, kidney mass, WAT mass, circulating leptin and antimüllerian hormone, and altered glucose homeostasis. ARV-110-H increased kidney (UACR, KIM-1, NGAL) and liver (ALT, AST, LDH) injury markers and caused severe hepatomegaly, while ARV-110-L mostly spared those deleterious effects. Unbiased proteomics analysis revealed that ARV-110-H treatment severely affected the liver proteome and dysregulated multiple signaling and metabolic canonical pathways, while only minimal effects were observed with ARV-110-L treatment. In summary, our findings underscore the potential of AR PROTACs as a novel therapeutic approach for managing metabolic complications in PCOS, provided the dosing is carefully optimized to avoid adverse effects.

Indexed as

Polycystic Ovary SyndromeReceptors, AndrogenAnimalsDihydrotestosteroneDisease Models, AnimalFemaleHyperandrogenismLiverMiceMice, Inbred C57BLOvaryAR protein, mouseDihydrotestosteroneReceptors, Androgenandrogen receptorandrogenspolycystic ovary syndromePROTAC

Identifiers

PMID40437805
PMCPMC12120138

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.