Evidence map›Paper›PMID 41062626›Full record

ArticleScientific reports2025

Chloroindazole based estrogen receptor β ligands with favorable pharmacokinetics promote functional remyelination and visual recovery.

Micah Feri, Sung Hoon Kim, Flavio D Cardenas, Alyssa M Anderson, Brandon T Poole, Devang Deshpande, Shane Desfor, Kelley C Atkinson, Stephanie R Peterson, Kendall W Nettles and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

20 authors.

Micah FeriDivision of Biomedical Sciences, School of Medicine at University of California at Riverside, Room 205, 311 School of Medicine Research Building, 900 University Ave, Riverside, CA, 92521, USA.
Sung Hoon KimDepartment of Chemistry, and Cancer Center, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Flavio D CardenasDivision of Biomedical Sciences, School of Medicine at University of California at Riverside, Room 205, 311 School of Medicine Research Building, 900 University Ave, Riverside, CA, 92521, USA.
Alyssa M AndersonDivision of Biomedical Sciences, School of Medicine at University of California at Riverside, Room 205, 311 School of Medicine Research Building, 900 University Ave, Riverside, CA, 92521, USA.
Brandon T PooleDivision of Biomedical Sciences, School of Medicine at University of California at Riverside, Room 205, 311 School of Medicine Research Building, 900 University Ave, Riverside, CA, 92521, USA.
Devang DeshpandeDivision of Biomedical Sciences, School of Medicine at University of California at Riverside, Room 205, 311 School of Medicine Research Building, 900 University Ave, Riverside, CA, 92521, USA.
Shane DesforDivision of Biomedical Sciences, School of Medicine at University of California at Riverside, Room 205, 311 School of Medicine Research Building, 900 University Ave, Riverside, CA, 92521, USA.
Kelley C AtkinsonDivision of Biomedical Sciences, School of Medicine at University of California at Riverside, Room 205, 311 School of Medicine Research Building, 900 University Ave, Riverside, CA, 92521, USA.
Stephanie R PetersonDivision of Biomedical Sciences, School of Medicine at University of California at Riverside, Room 205, 311 School of Medicine Research Building, 900 University Ave, Riverside, CA, 92521, USA.
Kendall W NettlesDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, 33458, USA.
Jerome C NwachukwuDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, 33458, USA.
Moyinoluwa T AjayiDivision of Biomedical Sciences, School of Medicine at University of California at Riverside, Room 205, 311 School of Medicine Research Building, 900 University Ave, Riverside, CA, 92521, USA.
Fernando BeltranDivision of Biomedical Sciences, School of Medicine at University of California at Riverside, Room 205, 311 School of Medicine Research Building, 900 University Ave, Riverside, CA, 92521, USA.
David E MartinCadenza Bio, Oklahoma City, Yukon, OK, 73120, USA.
Julio TapiaDivision of Biomedical Sciences, School of Medicine at University of California at Riverside, Room 205, 311 School of Medicine Research Building, 900 University Ave, Riverside, CA, 92521, USA.
Carol D CurtisCadenza Bio, Oklahoma City, Yukon, OK, 73120, USA.
Martin I Garcia-CastroDivision of Biomedical Sciences, School of Medicine at University of California at Riverside, Room 205, 311 School of Medicine Research Building, 900 University Ave, Riverside, CA, 92521, USA.
Benita S KatzenellenbogenDepartments of Molecular and Integrative Physiology, Cell and Developmental Biology, and Cancer Center, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
John A KatzenellenbogenDepartment of Chemistry, and Cancer Center, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Seema K Tiwari-WoodruffDivision of Biomedical Sciences, School of Medicine at University of California at Riverside, Room 205, 311 School of Medicine Research Building, 900 University Ave, Riverside, CA, 92521, USA. seema.tiwari-woodruff@medsch.ucr.edu.

Funding

MOLECULAR PROBES FOR STEROID RECEPTORSR37DK015556 · NIDDK · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI KATZENELLENBOGEN, JOHN A. · 1987 to 2012
$4.4M
Chemical, structural and molecular rules for fully antagonizing the estrogen receptorR01CA220284 · NCI · UNIVERSITY OF FLORIDA · PI KATZENELLENBOGEN, BENITA S, KATZENELLENBOGEN, JOHN A. · 2018 to 2022
$2.8M
Demyelination is coupled to neuronal hyperexcitability leading to seizuresR01NS111552 · NINDS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI BINDER, DEVIN K, TIWARI-WOODRUFF, SEEMA K · 2020 to 2024
$1.9M
Novel Ligands and Mechanisms to Achieve Selective Nuclear Receptor ActivityR01DK015556 · NIDDK · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI KATZENELLENBOGEN, JOHN A. · 1986 to 2016
$1.6M
Stimulating oligodendrocyte progenitor cell differentiation and remyelinationR01NS081141 · NINDS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI TIWARI-WOODRUFF, SEEMA K · 2014 to 2017
$1.3M
National Multiple Sclerosis Society FF-1811-32771NCI NIH HHS R01 CA220284NIDDK NIH HHS R01 DK015556NIDDK NIH HHS R37 DK015556NIH HHS DK015556NIH HHS NS081141- 01A1NINDS NIH HHS R01 NS081141NINDS NIH HHS R01 NS111552
6 · The paper itself

Abstract

Multiple sclerosis (MS) is a chronic autoimmune, demyelinating, and neurodegenerative disease that results in motor, visual, and cognitive deficits. While existing treatments can slow disease progression, they rarely restore lost neurological function or significantly enhance quality of life. Estrogen receptor β (ERβ) has emerged as a promising therapeutic target due to its ability to activate non-classical signaling pathways involved in neuroprotection, immune modulation, and remyelination. In this study, two chloroindazole-based ERβ-selective ligands, K102 and K110, were identified for their favorable pharmacokinetic profiles and performance in preclinical absorption, distribution, metabolism, and elimination (ADME) screening. These compounds demonstrated biological activity by promoting oligodendrocyte (OL) differentiation in both primary mouse and human OL cultures. In vivo, they enhanced axonal remyelination and improved functional electrophysiological outcomes in two mouse models of MS: experimental autoimmune encephalomyelitis (EAE) and cuprizone diet-induced demyelination. Additionally, K102 and K110 modulated immune responses, supporting OL survival and contributing to motor and visual recovery in EAE mice. These findings provide compelling preclinical evidence for advancing K102 and K110 to clinical development. By simultaneously addressing neurodegeneration and inflammation through ERβ-mediated signaling, these compounds offer a novel and potentially transformative approach to MS therapy.

Indexed as

Encephalomyelitis, Autoimmune, ExperimentalEstrogen Receptor betaIndazolesMultiple SclerosisRemyelinationAnimalsCell DifferentiationDisease Models, AnimalFemaleHumansLigandsMiceMice, Inbred C57BLOligodendrogliaEstrogen Receptor betaIndazolesLigands

Identifiers

PMID41062626
PMCPMC12508063

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.