Evidence map›Paper›PMID 40124519›Full record

ArticleiScience2025

Identification of small molecule inhibitors of PPM1D using an integrated drug discovery platform.

Subrata Shaw, Wei Jiang, Jason Rush, Nancy Dumont, John Kim, Ritu Singh, Adam Skepner, Carol Khodier, Cerise Raffier, Zachary Murphy and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2025. 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
–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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Subrata ShawBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Wei JiangBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Jason RushBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Nancy DumontBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
John KimBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Ritu SinghBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Adam SkepnerBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Carol KhodierBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Cerise RaffierBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Zachary MurphyBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Ni YanBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Cameron SchluterBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Xiao YuBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Mateusz SzuchnickiBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Murugappan SathappaBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Josephine KahnDepartment of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Adam S SperlingBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Florence WagnerBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
David C McKinneyBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Alexandra E GouldBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Colin W GarvieBroad Institute of MIT and Harvard University, Cambridge, MA, USA.
Peter G MillerBroad Institute of MIT and Harvard University, Cambridge, MA, USA.

Funding

Defining mechanisms of thalidomide analog resistanceK08CA252174 · NCI · DANA-FARBER CANCER INST · PI SPERLING, ADAM · 2020 to 2024
$1.3M
Role of PPM1D and PPM1D mutations in hematopoiesis and response to stressK08CA263183 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI MILLER, PETER GRANT · 2021 to 2025
$1.1M
The role of SRCAP in therapy related clonal hematopoiesisR01DK141535 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI Adam Sperling · 2025 to 2026
$974k
NCI NIH HHS K08 CA252174NCI NIH HHS K08 CA263183NIDDK NIH HHS R01 DK141535
6 · The paper itself

Abstract

PPM1D is a serine/threonine phosphatase recurrently activated in cancer, regulates the DNA damage response (DDR), and suppresses p53. Though PPM1D inhibition impairs tumor growth in cancer models and is the subject of multiple drug discovery efforts, no PPM1D inhibitors with clinical potential have been identified. We screened 600,000 compounds in a displacement assay and generated a hit series with nanomolar activity. We optimized our leads using internally developed assays to interrogate PPM1D, p53, and the DDR and defined important structure-activity relationships. Using an

Indexed as

Biological sciencesDrugsHealth sciencesMedicineNatural sciencesPharmacology

Identifiers

PMID40124519
PMCPMC11930361

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.