Evidence map›Paper›PMID 31047753›Full record

ArticleBioorganic & medicinal chemistry letters2019

Position of lipidation influences anticancer activity of Smac analogs.

Ewa D Micewicz, Christine Nguyen, Alina Micewicz, Alan J Waring, William H McBride, Piotr Ruchala

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2019. 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, top 97% of its field
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, 0 citations in OpenAlex.

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 at 2 institutions in 1 country.

Ewa D MicewiczDepartment of Radiation Oncology, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Christine NguyenDepartment of Radiation Oncology, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Alina MicewiczDavid Geffen School of Medicine at UCLA, Volunteering Program, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Alan J WaringDepartment of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90502, USA.
William H McBrideDepartment of Radiation Oncology, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Piotr RuchalaDepartment of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024, USA; The Pasarow Mass Spectrometry Laboratory, The Jane and Terry Semel Institute for Neuroscience and Human Behavior, 760 Westwood Plaza, Los Angeles, CA 90024, USA. Electronic address: pruchala@mednet.ucla.edu.
University of California, Los Angeles · USHarbor–UCLA Medical Center · US

Funding

UCLA Center for Biological RadioprotectorsU19AI067769 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHUTE, JOHN P, MCBRIDE, WILLIAM H. · 2005 to 2019
$44.6M
NIAID NIH HHS U19 AI067769
6 · The paper itself

Abstract

A small group of lipid-conjugated Smac mimetics was synthesized to probe the influence of the position of lipidation on overall anti-cancer activity. Specifically, new compounds were modified with lipid(s) in position 3 and C-terminus. Previously described position 2 lipidated analog M11 was also synthesized. The resulting mini library of Smacs lipidated in positions 2, 3 and C-terminus was screened extensively in vitro against a total number of 50 diverse cancer cell lines revealing that both the position of lipidation as well as the type of lipid, influence their anti-cancer activity and cancer type specificity. Moreover, when used in combination therapy with inhibitor of menin-MLL1 protein interactions, position 2 modified analog SM2 showed strong synergistic anti-cancer properties. The most promising lipid-conjugated analogs SM2 and SM6, showed favorable pharmacokinetics and in vivo activity while administered subcutaneously in the preclinical mouse model. Collectively, our findings suggest that lipid modification of Smacs may be a viable approach in the development of anti-cancer therapeutic leads.

Indexed as

Antineoplastic AgentsApoptosis Regulatory ProteinsCell Line, TumorHumansMitochondrial ProteinsNeoplasmsAntineoplastic AgentsApoptosis Regulatory ProteinsDIABLO protein, humanMitochondrial ProteinsAnticancer agentsApoptosisInhibitor of menin–MLL1 protein interactionsLipid-conjugated peptidesS-alkylation of peptidesSmac mimetics

Identifiers

PMID31047753
PMCPMC6625762
OpenAlexW2941287667

What OpenQuestion holds

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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.