Evidence map›Paper›PMID 39680643›Full record

ArticleJournal of medicinal chemistry2025

Structure-Based Development of Novel Spiro-Piperidine ASH1L Inhibitors.

Guang Huang, Rhiannon Stevens, Devon G Hucek, Trupta Purohit, Shuangjiang Li, Hongzhi Miao, Elise Trost, Geoff Hewett, Bradley Clegg, Se Ra Park and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medicinal chemistry, 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. 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

15 authors.

Guang HuangDepartment of Pathology, University of Michigan, Ann Arbor, Michigan 48109, United States.ORCID 0000-0001-7226-5743
Rhiannon StevensDepartment of Pathology, University of Michigan, Ann Arbor, Michigan 48109, United States.
Devon G HucekDepartment of Pathology, University of Michigan, Ann Arbor, Michigan 48109, United States.
Trupta PurohitDepartment of Pathology, University of Michigan, Ann Arbor, Michigan 48109, United States.
Shuangjiang LiDepartment of Pathology, University of Michigan, Ann Arbor, Michigan 48109, United States.
Hongzhi MiaoDepartment of Pathology, University of Michigan, Ann Arbor, Michigan 48109, United States.
Elise TrostDepartment of Pathology, University of Michigan, Ann Arbor, Michigan 48109, United States.
Geoff HewettDepartment of Pathology, University of Michigan, Ann Arbor, Michigan 48109, United States.
Bradley CleggDepartment of Pathology, University of Michigan, Ann Arbor, Michigan 48109, United States.
Se Ra ParkDepartment of Pathology, University of Michigan, Ann Arbor, Michigan 48109, United States.
Krishani RajanayakeCollege of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.
Bo WenCollege of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.
Duxin SunCollege of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.ORCID 0000-0002-6406-2126
Tomasz CierpickiDepartment of Pathology, University of Michigan, Ann Arbor, Michigan 48109, United States.ORCID 0000-0003-2058-0658
Jolanta GrembeckaDepartment of Pathology, University of Michigan, Ann Arbor, Michigan 48109, United States.ORCID 0000-0002-6180-9095

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2M
Michigan Chemistry-Biology Interface Training ProgramT32GM132046 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Emily E Scott, Wenjing Wang · 2019 to 2026
$4.1M
Development of ASH1L inhibitors for acute leukemiaR01CA244254 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GREMBECKA, JOLANTA · 2020 to 2024
$2.8M
Targeting Menin in Acute Leukemia with Upregulated HOX GenesR01CA272561 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jolanta Grembecka · 2023 to 2026
$2.5M
Targeting PRC1 in leukemiaR01CA282082 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Tomasz Cierpicki · 2023 to 2026
$2.5M
Targeting NSD1 in leukemiaR01CA226759 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CIERPICKI, TOMASZ · 2019 to 2023
$2.3M
Screening for inhibitors of NSD3 as a treatment for lung cancerR01CA276074 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jolanta Grembecka · 2023 to 2026
$2.0M
Development of chemical probe targeting NSD3 SET domain in breast cancerR01CA285304 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Tomasz Cierpicki · 2024 to 2026
$1.7M
NCI NIH HHS P30 CA046592NCI NIH HHS R01 CA226759NCI NIH HHS R01 CA244254NCI NIH HHS R01 CA272561NCI NIH HHS R01 CA276074NCI NIH HHS R01 CA282082NCI NIH HHS R01 CA285304NIGMS NIH HHS T32 GM132046
6 · The paper itself

Abstract

The absent, small, or homeotic-like 1 (ASH1L) protein is a histone lysine methyltransferase that plays a crucial role in various cancers, including leukemia. Despite representing an attractive therapeutic target, only one class of ASH1L inhibitors was identified to date. Herein, we report development of advanced ASH1L inhibitors targeting the catalytic SET domain, which were designed to access previously unexplored binding pocket on ASH1L. Extensive medicinal chemistry combined with structure-based design led to identification of

Indexed as

Cell ProliferationDNA-Binding ProteinsHistone-Lysine N-MethyltransferaseAntineoplastic AgentsApoptosisCell Line, TumorEnzyme InhibitorsHumansMolecular StructurePiperidinesSpiro CompoundsStructure-Activity RelationshipTranscription FactorsAntineoplastic AgentsASH1L protein, humanDNA-Binding ProteinsEnzyme InhibitorsHistone-Lysine N-MethyltransferasepiperidinePiperidinesSpiro CompoundsTranscription Factors

Identifiers

PMID39680643
PMCPMC12013431

What OpenQuestion holds

Textmetadata
LicenceTDM
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.