Evidence map›Paper›PMID 39934397›Full record

ArticleNature chemical biology2025

Pharmacodynamics of Akt drugs revealed by a kinase-modulated bioluminescent indicator.

Yan Wu, Chenzhou Hao, Chao Gao, Matt Hageman, Sungmoo Lee, Thomas A Kirkland, Nathanael S Gray, Yichi Su, Michael Z Lin

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. The last piece in fucosylation.Nature chemical biology · 2025
    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

9 authors.

Yan WuDepartment of Bioengineering, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-2596-1943
Chenzhou HaoDepartment of Neurobiology, Stanford University, Stanford, CA, USA.
Chao GaoPromega Corporation, San Luis Obispo, CA, USA.ORCID http://orcid.org/0000-0003-3662-6518
Matt HagemanPromega Corporation, San Luis Obispo, CA, USA.
Sungmoo LeeDepartment of Neurobiology, Stanford University, Stanford, CA, USA.
Thomas A KirklandPromega Corporation, Madison, WI, USA.ORCID http://orcid.org/0000-0003-0859-5785
Nathanael S GrayDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-5354-7403
Yichi SuDepartment of Nuclear Medicine, Zhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China. yichisu@fudan.edu.cn.ORCID http://orcid.org/0000-0001-5715-835X
Michael Z LinDepartment of Bioengineering, Stanford University, Stanford, CA, USA. mzlin@stanford.edu.ORCID http://orcid.org/0000-0002-0492-1961

Funding

Noninvasive bioluminescent imaging of neuronal activity in freely behaving animalsR21DA048252 · NIDA · STANFORD UNIVERSITY · PI LIN, MICHAEL Z. · 2019 to 2020
$435k
Bioluminescent indicators for noninvasive imaging of acetylcholine releaseR21NS122055 · NINDS · STANFORD UNIVERSITY · PI LIN, MICHAEL Z. · 2021 to 2021
$434k
NIDA NIH HHS R21 DA048252NINDS NIH HHS R21 NS122055U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) 1R21NS122055U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) 1R21DA048252
6 · The paper itself

Abstract

Measuring pharmacodynamics (PD)-the biochemical effects of drug dosing-and correlating them with therapeutic efficacy in animal models is crucial for the development of effective drugs but traditional PD studies are labor and resource intensive. Here we developed a kinase-modulated bioluminescent indicator (KiMBI) for rapid, noninvasive PD assessment of Akt-targeted drugs, minimizing drug and animal use. Using KiMBI, we performed a structure-PD relationship analysis on the brain-active Akt inhibitor ipatasertib by generating and characterizing two novel analogs. One analog, ML-B01, successfully inhibited Akt in both the brain and the body. Interestingly, capivasertib, ipatasertib and ML-B01 all exhibited PD durations beyond their pharmacokinetic profiles. Furthermore, KiMBI revealed that the PD effects of an Akt-targeted proteolysis-targeting chimera degrader endured for over 3 days. Thus, bioluminescence imaging with Akt KiMBI provides a noninvasive and efficient method for in vivo visualization of the PD of Akt inhibitors and degraders.

Indexed as

Luminescent MeasurementsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktPyrimidinesAnimalsBrainHumansMicePiperazinesPyrrolesStructure-Activity RelationshipcapivasertibipatasertibPiperazinesProtein Kinase InhibitorsProto-Oncogene Proteins c-aktPyrimidinesPyrroles

Identifiers

PMID39934397
PMCPMC13142969

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Registered trials

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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.