Evidence mapPaperPMID 40946227Full record

ArticleChemMedChem2025

Impact of C18 Epimerization of Indole- and Pyrazole-Fused 18β-Glycyrrhetinic Acid Derivatives on PTP1B and TCPTP Inhibitory Activity: Synthesis, In Vitro, and In Silico Studies.

Ledy De-la-Cruz-Martínez, Rosendo Martínez-Arellano, Mitzi López-Sánchez, José G Alvarado-Rodríguez, Jesús Martin Torres-Valencia, David Equihua-González, Julio-César Almanza-Pérez, Jaime Pérez-Villanueva, Martín González-Andrade, José C Páez-Franco and 1 more

Abstract read
In one paragraph

Article in ChemMedChem, 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. Article
  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

11 authors.

Ledy De-la-Cruz-MartínezDoctorado en Ciencias Farmacéuticas, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Unidad Xochimilco, Ciudad de México, 04960, Mexico.
Rosendo Martínez-ArellanoLaboratorio de Síntesis y Aislamiento de Sustancias Bioactivas, Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Unidad Xochimilco, Ciudad de México, 04960, Mexico.
Mitzi López-SánchezLaboratorio de Síntesis y Aislamiento de Sustancias Bioactivas, Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Unidad Xochimilco, Ciudad de México, 04960, Mexico.
José G Alvarado-RodríguezÁrea Académica de Química, Universidad Autónoma del Estado de Hidalgo, Hidalgo, 42184, Mexico.ORCID https://orcid.org/0000-0001-5390-4255
Jesús Martin Torres-ValenciaÁrea Académica de Química, Universidad Autónoma del Estado de Hidalgo, Hidalgo, 42184, Mexico.ORCID https://orcid.org/0000-0001-6426-7562
David Equihua-GonzálezLaboratorio de Síntesis y Aislamiento de Sustancias Bioactivas, Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Unidad Xochimilco, Ciudad de México, 04960, Mexico.
Julio-César Almanza-PérezLaboratorio de Farmacología, Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Unidad Iztapalapa, Ciudad de México, 09340, Mexico.
Jaime Pérez-VillanuevaLaboratorio de Síntesis y Aislamiento de Sustancias Bioactivas, Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Unidad Xochimilco, Ciudad de México, 04960, Mexico.ORCID https://orcid.org/0000-0001-5777-2536
Martín González-AndradeLaboratorio de Biosensores y Modelaje Molecular, Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico.ORCID https://orcid.org/0000-0002-8910-3035
José C Páez-FrancoRed de apoyo a la Investigación, Universidad Nacional Autónoma de México, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, 14080, Mexico.ORCID https://orcid.org/0000-0001-7717-420X
Francisco Cortés-BenítezLaboratorio de Síntesis y Aislamiento de Sustancias Bioactivas, Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Unidad Xochimilco, Ciudad de México, 04960, Mexico.ORCID https://orcid.org/0000-0002-3954-8220

Funding

DGAPA-UNAM IN205025DGAPA-UNAM PAPIIT-IN203222DGTIC-UNAM LANCAD-UNAM-DGTIC-313Secretaría de Ciencia, Humanidades, Tecnología e Innovación CF-2023-I-186
6 · The paper itself

Abstract

Protein tyrosine phosphatase 1B (PTP1B) is crucial for negatively regulating the canonical insulin and leptin signaling pathways. This enzyme is a validated target for treating various disorders, including diabetes and obesity. However, to date, no PTP1B inhibitors have been approved for use. In earlier studies, we developed two modified versions of 18β-glycyrrhetinic acid (18β-GA) called FC-114 and FC-122, which showed better inhibitory PTP1B activity than ursolic acid, a well-known inhibitor. To develop even stronger inhibitors, we looked at another compound, 18α-glycyrrhetinic acid (18α-GA), which is more potent than 18β-GA. Thus, in this study, we aimed to synthesize the analogs 18epi-FC114 (3c) and 18epi-FC-122 (5c). These compounds were prepared with and without the carbonyl group at C11. The results showed that converting 18β-H to 18α-H, as well as the absence of the 11-carbonyl group, negatively impacted the PTP1B inhibitory activity. However, the synthesized compounds exhibited an uncompetitive type of inhibition toward PTP1B and did not inhibit the TCPTP enzyme. Molecular docking and dynamics simulations suggest that the inversion of 18β-H pushes the 30-COOH group away, disrupting interactions at the C-terminal site of PTP1B

Indexed as

Enzyme InhibitorsGlycyrrhetinic AcidIndolesProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine Phosphatase, Non-Receptor Type 2PyrazolesDose-Response Relationship, DrugHumansMolecular Docking SimulationMolecular StructureStructure-Activity Relationship18alpha-glycyrrhetinic acidEnzyme InhibitorsGlycyrrhetinic AcidindoleIndolesProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine Phosphatase, Non-Receptor Type 2PTPN1 protein, humanPyrazolesGlycyrrhetinic acidMolecular dockingMolecular dynamics simulationsProtein tyrosine phosphatase 1BUncompetitive inhibition

Identifiers

PMID40946227
PMCPMC12640663

What Socratic holds

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Registered trials

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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.