Evidence map›Paper›PMID 35657291›Full record

ArticleJournal of medicinal chemistry2022

Optimizing Shape Complementarity Enables the Discovery of Potent Tricyclic BCL6 Inhibitors.

Owen A Davis, Kwai-Ming J Cheung, Alfie Brennan, Matthew G Lloyd, Matthew J Rodrigues, Olivier A Pierrat, Gavin W Collie, Yann-Vaï Le Bihan, Rosemary Huckvale, Alice C Harnden and 15 more

Abstract read
In one paragraph

Article in Journal of medicinal chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Article
  2. Review
  3. Design and synthesis of novelFuture medicinal chemistry · 2025
    Article
  4. Review
  5. Article
  6. Article
  7. Determination of Ligand-Binding Affinity (Journal of medicinal chemistry · 2023
    Article
  8. Article
  9. Discovery of anJournal of medicinal chemistry · 2023
    Article
  10. 30th Annual GPPharmaceuticals (Basel, Switzerland) · 2023
    Article
  11. Article
  12. Article
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

25 authors.

Owen A DavisCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
Kwai-Ming J CheungCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
Alfie BrennanCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
Matthew G LloydCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..ORCID 0000-0001-7100-3469
Matthew J RodriguesCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
Olivier A PierratCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
Gavin W CollieCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..ORCID 0000-0002-0406-922X
Yann-Vaï Le BihanCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..ORCID 0000-0002-6850-9706
Rosemary HuckvaleCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
Alice C HarndenCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..ORCID 0000-0002-4092-705X
Ana VarelaCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
Michael D BrightCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
Paul EveCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
Angela HayesCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
Alan T HenleyCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
Michael D CarterCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
P Craig McAndrewCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
Rachel TalbotCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
Rosemary BurkeCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
Rob L M van MontfortCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
Florence I RaynaudCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..ORCID 0000-0003-0957-6279
Olivia W RossaneseCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..
Mirco MeniconiCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..ORCID 0000-0001-9919-8472
Benjamin R BellenieCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..ORCID 0000-0001-9987-3079
Swen HoelderCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, U.K..ORCID 0000-0001-8636-1488

Funding

Cancer Research UK 22897Cancer Research UK C309/A11566
6 · The paper itself

Abstract

To identify new chemical series with enhanced binding affinity to the BTB domain of B-cell lymphoma 6 protein, we targeted a subpocket adjacent to Val18. With no opportunities for strong polar interactions, we focused on attaining close shape complementarity by ring fusion onto our quinolinone lead series. Following exploration of different sized rings, we identified a conformationally restricted core which optimally filled the available space, leading to potent BCL6 inhibitors. Through X-ray structure-guided design, combined with efficient synthetic chemistry to make the resulting novel core structures, a >300-fold improvement in activity was obtained by the addition of seven heavy atoms.

Indexed as

BTB-POZ DomainProtein BindingProto-Oncogene Proteins c-bcl-6Proto-Oncogene Proteins c-bcl-6

Identifiers

PMID35657291
PMCPMC9234963

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.