Evidence map›Paper›PMID 39029437›Full record

ArticleBioorganic & medicinal chemistry2024

Structural modification of the propyl linker of cjoc42 in combination with sulfonate ester and triazole replacements for enhanced gankyrin binding and anti-proliferative activity.

Tejashri Chavan, Dipti Kanabar, Kinjal Patel, Taylor M Laflamme, Maryam Riyazi, Donald E Spratt, Aaron Muth

Abstract read
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In one paragraph

Article in Bioorganic & medicinal chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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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

7 authors.

Tejashri ChavanDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, USA.
Dipti KanabarDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, USA.
Kinjal PatelDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, USA.
Taylor M LaflammeGustaf H. Carlson School of Chemistry & Biochemistry, Clark University, Worcester, MA 01610, USA.
Maryam RiyaziGustaf H. Carlson School of Chemistry & Biochemistry, Clark University, Worcester, MA 01610, USA.
Donald E SprattGustaf H. Carlson School of Chemistry & Biochemistry, Clark University, Worcester, MA 01610, USA.
Aaron MuthDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, USA. Electronic address: mutha@stjohns.edu.

Funding

Structure and Mechanism of HERC5-dependent ISGylationR15GM126432 · NIGMS · CLARK UNIVERSITY (WORCESTER, MA) · PI SPRATT, DONALD ERIC · 2017 to 2023
$1000k
Developing Chemical Probes to Decipher Gankyrin BiologySC2GM139672 · NIGMS · ST. JOHN'S UNIVERSITY · PI MUTH, AARON · 2021 to 2023
$492k
NIGMS NIH HHS R15 GM126432NIGMS NIH HHS SC2 GM139672
6 · The paper itself

Abstract

Liver cancer is a complex disease that involves various oncoproteins and the inactivation of tumor suppressor proteins (TSPs). Gankyrin is one such oncoprotein, first identified in human hepatocellular carcinoma, that is known to inactivate multiple TSPs, leading to proliferation and metastasis of tumor cells. Despite this, there has been limited development of small molecule gankyrin binders for the treatment of liver cancer. In this study, we are reporting the structure-based design of gankyrin-binding small molecules which inhibit the proliferation of HuH6 and HepG2 cells while also increasing the levels of certain TSPs, such as Rb and p53. Interestingly the first molecule to exhibit inhibition by 3D structure stabilization is seen. These results suggest a possible mechanism for small-molecule inhibition of gankyrin and demonstrate that gankyrin is a viable therapeutic target for the treatment of liver cancer.

Indexed as

Antineoplastic AgentsCell ProliferationProto-Oncogene ProteinsTriazolesBenzenesulfonatesCell Line, TumorDose-Response Relationship, DrugDrug Screening Assays, AntitumorEstersHumansLiver NeoplasmsMolecular StructureProteasome Endopeptidase ComplexStructure-Activity RelationshipSulfonic AcidsAntineoplastic AgentsBenzenesulfonatescjoc42 compoundEstersProteasome Endopeptidase ComplexProto-Oncogene ProteinsPSMD10 protein, humanSulfonic AcidsTriazolesGankyrinLiver cancerProteasomeProtein-protein interactions

Identifiers

PMID39029437
PMCPMC11342405

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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 OpenQuestion graph.