ArticleJournal of medicinal chemistry2025
Discovery and Optimization of LATS1 and LATS2 Kinase Inhibitors for Use in Regenerative Medicine.
Patrick J Morris, Damien Y Duveau, Michele Ceribelli, Frances Anne Tosto, Dara N Love, Bridget S Scherer, Dingyin Tao, Yuhong Fang, Lale Evsen, Samuel A Kotler and 4 more
Abstract read
In one paragraphArticle in Journal of medicinal chemistry, 2025. 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
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 registryThe 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 literatureWho cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
4 · The recordCorrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what moneyAuthors and funding
14 authors.
Patrick J MorrisDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.ORCID 0000-0003-2380-4178 Damien Y DuveauDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
Michele CeribelliDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
Frances Anne TostoDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.ORCID 0000-0003-1109-7103 Dara N LoveDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
Bridget S SchererDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
Dingyin TaoDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.ORCID 0000-0001-6531-2740 Yuhong FangDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
Lale EvsenDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.ORCID 0009-0003-2417-3598 Samuel A KotlerDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
Christopher A LeClairDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.ORCID 0000-0002-2746-5938 Ganesha RaiDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.ORCID 0000-0001-9763-9641 Craig J ThomasDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.ORCID 0000-0001-9386-9001 Scott B HoytDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.ORCID 0009-0009-9788-1935 Funding
Bioactive small molecule development- IRAK-FLT3 programZIATR000472 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI THOMAS, CRAIG · 2023 to 2025
$3.9MIntramural NIH HHS ZIA TR000472
6 · The paper itselfAbstract
The Large Tumor Suppressor Kinases 1 and 2 (LATS1/2) are serine/threonine kinases that play an essential role in Hippo pathway activation and influence multiple physiological events ranging from organ growth to tissue regeneration. As a result, pharmacological inhibition of LATS1/2 represents a promising strategy for therapeutic intervention in multiple indications. Within, we present the discovery of potent and selective inhibitors of the kinases LATS1 and LATS2. Using a scaffold hopping strategy from the reported AKT inhibitor AT-7867 (1) we pursued a series of structure activity relationship (SAR) studies that dramatically improved potency versus LATS1 and LATS2, while concurrently improving kinome-wide selectivity. ADME properties were further optimized via introduction of conformational restriction into the target molecule, to lead to compound 27 which possesses potent inhibitory activity against both LATS1 and LATS2 and proof of concept activity in wound healing models.
Indexed as
Drug DiscoveryProtein Kinase InhibitorsProtein Serine-Threonine KinasesRegenerative MedicineTumor Suppressor ProteinsAnimalsHumansMiceStructure-Activity RelationshipWound HealingLATS1 protein, humanLATS2 protein, humanProtein Kinase InhibitorsProtein Serine-Threonine KinasesTumor Suppressor Proteins
Identifiers
PMID40768682
PMCPMC12406206
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390