Evidence map›Paper›PMID 38464204›Full record

ArticlebioRxiv : the preprint server for biology2024

PROTAC-mediated dual degradation of BCL-xL and BCL-2 is a highly effective therapeutic strategy in small-cell lung cancer.

Sajid Khan, Lin Cao, Janet Wiegand, Peiyi Zhang, Maria Zajac-Kaye, Frederic J Kaye, Guangrong Zheng, Daohong Zhou

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

Article in bioRxiv : the preprint server for biology, 2024. 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, 5 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Sajid KhanDepartment of Biochemistry & Structural Biology, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Lin CaoDepartment of Biochemistry & Structural Biology, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Janet WiegandDepartment of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Peiyi ZhangDepartment of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Maria Zajac-KayeDepartment of Anatomy & Cell Biology, College of Medicine, University of Florida, Gainesville, Florida, USA.
Frederic J KayeDivision of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA.
Guangrong ZhengDepartment of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Daohong ZhouDepartment of Biochemistry & Structural Biology, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
University of Florida · USThe University of Texas Health Science Center at San Antonio · US

Funding

Inhibition of Bcl-xL by Targeted DegradationR01CA241191 · NCI · UNIVERSITY OF FLORIDA · PI KONOPLEVA, MARINA Y, ZHENG, GUANGRONG · 2020 to 2024
$2.6M
Use of BCL-xL Proteolysis targeting chimeras to treat pancreatic cancerR01CA242003 · NCI · UNIVERSITY OF FLORIDA · PI TREVINO, JOSE G., ZHENG, GUANGRONG · 2019 to 2023
$2.6M
NCI NIH HHS R01 CA241191NCI NIH HHS R01 CA242003
6 · The paper itself

Abstract

BCL-xL and BCL-2 are validated therapeutic targets in small-cell lung cancer (SCLC). Targeting these proteins with navitoclax (formerly ABT263, a dual BCL-xL/2 inhibitor) induces dose-limiting thrombocytopenia through on-target BCL-xL inhibition in platelets. Therefore, platelet toxicity poses a barrier in advancing the clinical translation of navitoclax. We have developed a strategy to selectively target BCL-xL in tumors, while sparing platelets, by utilizing proteolysis-targeting chimeras (PROTACs) that hijack the cellular ubiquitin proteasome system for target ubiquitination and subsequent degradation. In our previous study, the first-in-class BCL-xL PROTAC, called DT2216, was shown to have synergistic antitumor activities when combined with venetoclax (formerly ABT199, BCL-2-selective inhibitor) in a BCL-xL/2 co-dependent SCLC cell line, NCI-H146 (hereafter referred to as H146),

Indexed as

ApoptosisBCL-2BCL-XLPROTACSmall-cell lung cancer

Identifiers

PMID38464204
PMCPMC10925307
OpenAlexW4392364479

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.