Evidence map›Paper›PMID 37663435›Full record

ArticleCancer research communications2023

Discovery and Characterization of ZL-2201, a Potent, Highly Selective, and Orally Bioavailable Small-molecule DNA-PK Inhibitor.

Shruti Lal, Neil E Bhola, Bee-Chun Sun, Yuping Chen, Tom Huang, Vivian Morton, Kevin X Chen, Shanghua Xia, Haoyu Zhang, Nehal S Parikh and 4 more

Open access · goldAbstract read
In one paragraph

Article in Cancer research communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.3field-weighted citation impact, top 36% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Review
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

14 authors at 2 institutions in 2 countries.

Shruti LalBiologics Discovery, Zai Lab (US) LLC, Menlo Park, California.ORCID 0009-0008-4517-3147
Neil E BholaBiologics Discovery, Zai Lab (US) LLC, Menlo Park, California.ORCID 0000-0003-3192-7514
Bee-Chun SunBiologics Discovery, Zai Lab (US) LLC, Menlo Park, California.ORCID 0009-0008-2182-7492
Yuping ChenBiologics Discovery, Zai Lab (US) LLC, Menlo Park, California.ORCID 0009-0000-0101-9713
Tom HuangBiologics Discovery, Zai Lab (US) LLC, Menlo Park, California.ORCID 0009-0005-8436-3099
Vivian MortonBiologics Discovery, Zai Lab (US) LLC, Menlo Park, California.ORCID 0000-0002-2026-464X
Kevin X ChenWuXi AppTec, Shanghai, P.R. China.ORCID 0009-0005-3156-6394
Shanghua XiaWuXi AppTec, Shanghai, P.R. China.ORCID 0009-0001-8812-2998
Haoyu ZhangWuXi AppTec, Shanghai, P.R. China.ORCID 0009-0000-5065-2937
Nehal S ParikhBiologics Discovery, Zai Lab (US) LLC, Menlo Park, California.ORCID 0000-0002-4746-1168
Qiuping YeBiologics Discovery, Zai Lab (US) LLC, Menlo Park, California.ORCID 0009-0008-9039-0124
O Petter VeibyBiologics Discovery, Zai Lab (US) LLC, Menlo Park, California.ORCID 0000-0001-6230-813X
David I BellovinBiologics Discovery, Zai Lab (US) LLC, Menlo Park, California.ORCID 0009-0008-5804-2816
Yuhua JiBiologics Discovery, Zai Lab (US) LLC, Menlo Park, California.ORCID 0009-0004-8483-2142
Meta (United States) · USWuXi AppTec (China) · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA-dependent protein kinase (DNA-PK), a driver of the non-homologous end-joining (NHEJ) DNA damage response pathway, plays an instrumental role in repairing double-strand breaks (DSB) induced by DNA-damaging poisons. We evaluate ZL-2201, an orally bioavailable, highly potent, and selective pharmacologic inhibitor of DNA-PK activity, for the treatment of human cancerous malignancies. ZL-2201 demonstrated greater selectivity for DNA-PK and effectively inhibited DNA-PK autophosphorylation in a concentration- and time-dependent manner. Initial data suggested a potential correlation between ataxia-telangiectasia mutated (ATM) deficiency and ZL-2201 sensitivity. More so, ZL-2201 showed strong synergy with topoisomerase II inhibitors independent of ATM status Significance: ZL-2201, a potent and selective DNA-PK inhibitor, can target tumor models in combination with DNA DSB-inducing agents such as radiation or doxorubicin, with potential to improve recurrent therapies in the clinic.

Indexed as

DNA-Activated Protein KinaseAdministration, OralAnimalsHumansPhosphorylationDNA-Activated Protein Kinase

Identifiers

PMID37663435
PMCPMC10473160
OpenAlexW4385697939

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.