Evidence mapPaperPMID 42445003Full record

ArticleACS medicinal chemistry letters2026

Design of PKC-Targeting Benzolactams as Gli Inhibitors.

Marianna Haddad, Jo Chvatal, Alexandria Kifer, Jayannah Herdrich, McCarthy Poljak, Kelvin L Billingsley

Abstract read
In one paragraph

Article in ACS medicinal chemistry letters, 2026. 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

6 authors.

Marianna HaddadDepartment of Chemistry and Biochemistry, Loyola University Chicago, Chicago, Illinois 60660, United States.
Jo ChvatalDepartment of Chemistry and Biochemistry, Loyola University Chicago, Chicago, Illinois 60660, United States.
Alexandria KiferDepartment of Chemistry and Biochemistry, Loyola University Chicago, Chicago, Illinois 60660, United States.
Jayannah HerdrichDepartment of Chemistry and Biochemistry, Loyola University Chicago, Chicago, Illinois 60660, United States.ORCID https://orcid.org/0009-0004-8995-0711
McCarthy PoljakDepartment of Chemistry and Biochemistry, Loyola University Chicago, Chicago, Illinois 60660, United States.
Kelvin L BillingsleyDepartment of Chemistry and Biochemistry, Loyola University Chicago, Chicago, Illinois 60660, United States.ORCID https://orcid.org/0000-0001-9071-5170

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dysregulated Hedgehog signaling, driven by oncogenic Gli transcription factors, plays a central role in many cancers and other Gli-dependent diseases. Inhibition of Gli through Smoothened-independent mechanisms represents a promising strategy to overcome resistance to clinical Hedgehog pathway inhibitors. Herein we report the synthesis and structure-activity relationship analysis of benzolactam analogues derived from TPPB, a potent inhibitor of Gli signaling that suppresses Gli activity via a protein kinase C (PKC)-mediated mechanism. Strategic chemical modifications were introduced across positions of the benzolactam core to assess their effects on biological activity using Gli-reporter cell-based assays. Our findings identified key structural features required for PKC-mediated Gli inhibition, and computational modeling revealed novel interactions between the PKC C1 domain and benzolactam analogues with nanomolar potency. Together, these studies provide a framework for designing therapeutics targeting Gli-driven diseases resistant to current treatments.

Indexed as

BenzolactamGli transcription factorsHedgehog signaling pathwayInhibitorProtein kinase CStructure−activity relationship

Identifiers

PMID42445003
PMCPMC13358976

What Socratic holds

Textmetadata
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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.