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Protein / target

RAC-gamma serine/threonine-protein kinase

Encoded byAKT3Q9Y243Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Advanced Clinical

Protein at a glance

Biological role

Protein serine/threonine kinase

Strongest disease association

Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus

Via encoding gene AKT3 · Genetic literature evidence · score 0.94

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis.

View complete UniProt function annotation

AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis

Subcellular location

NucleusCytoplasmMembrane
Domains and Gene Ontology detail (23)

Domains & features

PHProtein kinaseAGC-kinase C-terminal

Gene Ontology

  • Ccytosol
  • Cmembrane
  • Cnucleoplasm
  • FATP binding
  • Fprotein kinase activity
  • Fprotein serine kinase activity
  • Fprotein serine/threonine kinase activity
  • Pinsulin receptor signaling pathway
  • Pintracellular signal transduction
  • Pnegative regulation of apoptotic process
  • Pnegative regulation of cellular senescence
  • Pnegative regulation of PERK-mediated unfolded protein response

479 aa · 56 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell proliferation & survivalUniProt · ReactomeCell migrationGO · ReactomeReceptor tyrosine kinase signallingReactomeOncogenic signallingReactomeCell-cycle regulationReactomeApoptosis & cell deathUniProt · GO
View supporting evidence

Cell proliferation & survival

  • ·AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3)…
  • ·PIP3 activates AKT signaling
  • ·CD28 dependent PI3K/Akt signaling

Cell migration

  • ·positive regulation of blood vessel endothelial cell migration
  • ·positive regulation of cell migration involved in sprouting angiogenesis
  • ·RUNX2 regulates genes involved in cell migration

Receptor tyrosine kinase signalling

  • ·Downregulation of ERBB2:ERBB3 signaling

Oncogenic signalling

  • ·Constitutive Signaling by AKT1 E17K in Cancer

Cell-cycle regulation

  • ·Cyclin E associated events during G1/S transition

Apoptosis & cell death

  • ·AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3)…
  • ·negative regulation of apoptotic process
View underlying pathways (25)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

PHLPP2PHLPP1PIK3CAPIK3R1PIK3CGPIK3R3TSC2PIK3R2FOXO1MDM2AKT3

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

1 medicine · 2 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Breast Neoplasms1 medicine
Broader indication categories (1)
Neoplasms1 medicine

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

2

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

ipatasertib
Phase 3Inhibitor

Serine/threonine-protein kinase AKT inhibitor

Acts on a complex — shared with AKT2, AKT1 · 1 of 3 recorded protein targets — narrow recorded profile

capivasertib
ApprovedInhibitor

Serine/threonine-protein kinase AKT inhibitor

Indicated for Breast Neoplasms, Neoplasms

Acts on a complex — shared with AKT2, AKT1 · 1 of 3 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene AKT3

Gene-level evidence surfaced through the gene AKT3that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2
0.94Well supported

Genetic evidence dominant · Open Targets 0.80

Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus
0.81Well supported

Genetic literature evidence dominant · Open Targets 0.67

Schizophrenia
0.76Well supported

Genetic evidence dominant · Open Targets 0.46

Glioma
0.72Moderately supported

Genetic evidence dominant · Open Targets 0.44

Neoplasms
0.72Moderately supported

Clinical evidence dominant · Open Targets 0.45

View evidence synthesis (5)
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2Well supported
0.94
agreement 0.841.00
Genetic57%Somatic mutation29%Animal model13%Literature0%Genetic literaturedup

Open Targets aggregate 0.80 · 4 independent evidence families · 1 not counted as duplicate

Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalusWell supported
0.81
agreement 0.680.94
Genetic literature77%Animal model22%Literature1%Geneticdup

Open Targets aggregate 0.67 · 3 independent evidence families · 1 not counted as duplicate

SchizophreniaWell supported
0.76
agreement 0.620.89
Genetic91%Literature9%

Open Targets aggregate 0.46 · 2 independent evidence families

GliomaModerately supported
0.72
agreement 0.610.83
Genetic72%Somatic mutation22%Literature5%

Open Targets aggregate 0.44 · 3 independent evidence families

NeoplasmsModerately supported
0.72
agreement 0.610.83
Clinical46%Pathway24%Somatic mutation19%Literature11%

Open Targets aggregate 0.45 · 4 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 20.80
Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus0.67
Breast Neoplasms0.57
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 10.47
Schizophrenia0.46
overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes0.46
Neoplasms0.45
Glioma0.44
Risk-taking behaviour0.41

Drug development

13 compounds recorded · 1 approved · 12 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
XL-418Phase 1
MK-2206Phase 2
UPROSERTIBPhase 2
RUPITASERTIBPhase 1
CAPIVASERTIBApproval
MIRANSERTIBPhase 2
TAS0612Phase 1
LY-2780301Phase 1 2
AFURESERTIBPhase 3
IPATASERTIBPhase 3

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Advanced Clinical and High-Quality Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (literature and uniprot ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (11)
SM · Advanced ClinicalSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · Human Protein Atlas locPR · LiteraturePR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

heart diseaseForce et al. (2011)regulation of catalytic activityToxCast

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

RECRUITING · via capivasertib · NCT07294677

RECRUITING · via ipatasertib · NCT05564377

ACTIVE_NOT_RECRUITING · via ipatasertib · NCT06400251

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Indication expanded2026-06-12

    Indication expansion: CAPIVASERTIB (NDA218197)

    fda · regulatory · fda · via capivasertib

  2. Label change2026-05-27

    Label change: CAPIVASERTIB (NDA218197)

    fda · regulatory · fda · via capivasertib

  3. Label change2025-11-14

    Label change: CAPIVASERTIB (NDA218197)

    fda · regulatory · fda · via capivasertib

  4. Label change2025-02-13

    Label change: CAPIVASERTIB (NDA218197)

    fda · regulatory · fda · via capivasertib

  5. Label change2024-09-23

    Label change: CAPIVASERTIB (NDA218197)

    fda · regulatory · fda · via capivasertib

  6. Regulatory approval2024-06-17

    Approval: Truqap (EMA)

    ema · regulatory · ema · via capivasertib

  7. New publication2024-04-02
    Capivasertib: A Novel AKT Inhibitor Approved for Hormone-Receptor-Positive, HER-2-Negative Metastatic Breast Cancer.

    The Annals of pharmacotherapy · 2024 · 18 citations · Europe PMC · via capivasertib

  8. New publication2024-02-01
    First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer: Clinical and Biomarker Results.

    Clinical cancer research : an official journal of the American Association for Cancer Research · 2024 · 35 citations · Europe PMC · via ipatasertib

  9. Regulatory approval2023-11-16

    Approval: CAPIVASERTIB (NDA218197)

    fda · regulatory · fda · via capivasertib

  10. New publication2023-06-01
    Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer.

    The New England journal of medicine · 2023 · 539 citations · Europe PMC · via capivasertib

  11. New publication2020-09-10
    Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): a multicentre, multicohort, phase 2a, platform trial.

    The Lancet. Oncology · 2020 · 274 citations · Europe PMC · via capivasertib

  12. New publication2019-12-16
    Capivasertib Plus Paclitaxel Versus Placebo Plus Paclitaxel As First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020 · 304 citations · Europe PMC · via capivasertib

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.