Evidence map›Paper›PMID 40009150›Full record

ReviewMolecular diversity2025

Structural insights of AKT and its activation mechanism for drug development.

B Harish Kumar, Shama Prasada Kabekkodu, K Sreedhara Ranganath Pai

Abstract readReview
In one paragraph

Review in Molecular diversity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing 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

19 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Angiotensin II type 1 receptor signaling promotes bladder cancer progression and its inhibition by Losartan.Hypertension research : official journal of the Japanese Society of Hypertension · 2026
    Article
  8. Review
  9. Article
  10. Review
  11. Therapeutic Potential ofInternational journal of molecular sciences · 2025
    Article
  12. PI3 K/AKT/mTOR pathway and its role in breast cancer stem cells.Naunyn-Schmiedeberg's archives of pharmacology · 2025
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Exploring the bioactive compounds and molecular mechanisms of onion (Journal of advanced pharmaceutical technology & research
    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

3 authors.

B Harish KumarDepartment of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
Shama Prasada KabekkoduDepartment of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
K Sreedhara Ranganath PaiDepartment of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India. ksr.pai@manipal.edu.

Funding

Indian council of medical research 3/1/2/189/Neuro/2021-NCD-1
6 · The paper itself

Abstract

AKT1, a serine/threonine kinase, is pivotal in signaling and regulating cell survival, proliferation, and metabolism. This review focuses on the structural insights and the essential features required for its active conformation. AKT belongs to the AGC kinase group and has three isoforms: AKT1, AKT2, and AKT3. AKT has three functional regions: PH domain, kinase domain, and hydrophobic motif. AKT1 activation involves intricate conformational changes, including transitions in the αC-in, DFG-in, G-loop, activation loop, and PH domain out, S-spine and R-spine formation, as well as phosphorylation at Thr 308 and Ser 473, which enable AKT1 to adopt active conformation. The analysis highlights the limitations of the AlphaFold-predicted AKT1 structure, which lacks key elements of the active state, including ATP, magnesium ion coordination, phosphatidylinositol-(1,3,4,5)-tetraphosphate, substrate peptide, and phosphorylation at Thr 308 and Ser 473. This study underscores the necessity of these features for stabilizing the kinase domain and facilitating efficient substrate phosphorylation. By consolidating structural insights and activation mechanisms, this review aims to inform the development of computational models and targeted therapeutics for AKT1 activators in diseases such as hepatic ischemia-reperfusion injury, cerebral ischemia, acute hepatic failure, subarachnoid hemorrhage, and alzheimer's disease.

Indexed as

Drug DevelopmentProto-Oncogene Proteins c-aktAnimalsEnzyme ActivationHumansModels, MolecularPhosphorylationProtein ConformationProto-Oncogene Proteins c-aktAKT1 activationAKT active conformationAlphaFold’s limitationsAlphaFold structureHydrophobic motifPH domainPhosphorylation

Identifiers

PMID40009150
PMCPMC12638386

What OpenQuestion holds

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LicenceCC BY
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.