Protein / target

RAC-gamma serine/threonine-protein kinase

AKT3Q9Y243Homo sapiensSwiss-Prot
UniProt: Q9Y243Ensembl: ENSG00000117020HGNC: HGNC:393NCBI Gene: 10000
Clinically validated
Therapeutic maturity
1
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Advanced Clinical

Protein at a glance

Biological role

Protein serine/threonine kinase activity

Primary system

Cardiovascular system

Strongest disease association

Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus

Genetic literature evidence · score 0.94

Therapeutic maturity

Clinically validated target

1 approved medicine against this target

Druggability

Small molecule

Open Targets tractability · Advanced Clinical

Clinical development

1 approved · 12 in clinical development

30 linked trials

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

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.

Kinase signallingUniProt · GOApoptosis & cell deathUniProt · GOTranscriptional regulationReactome
View supporting evidence

Kinase signalling

  • ·AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3)…
  • ·protein kinase activity
  • ·protein serine kinase activity
  • ·protein serine/threonine kinase activity

Apoptosis & cell death

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

Transcriptional regulation

  • ·Regulation of localization of FOXO transcription factors
View underlying pathways (25)
Activation of BAD and translocation to mitochondria
PIP3 activates AKT signaling
Downregulation of ERBB2:ERBB3 signaling
MTOR signalling
Inhibition of TSC complex formation by AKT (PKB)
AKT phosphorylates targets in the cytosol
AKT phosphorylates targets in the nucleus
Negative regulation of the PI3K/AKT network
AKT-mediated inactivation of FOXO1A
CD28 dependent PI3K/Akt signaling
Co-inhibition by CTLA4
G beta:gamma signalling through PI3Kgamma
VEGFR2 mediated vascular permeability
TP53 Regulates Metabolic Genes
Constitutive Signaling by AKT1 E17K in Cancer

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.

Drugs targeting this protein

2

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

ipatasertib
Phase 3Inhibitor

Serine/threonine-protein kinase AKT inhibitor

Appears in clinical studies involving breast cancer, colorectal cancer, prostate cancer, triple-negative breast carcinoma

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

Appears in clinical studies involving breast cancer, breast neoplasm, neoplasm, triple-negative breast carcinoma

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

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus0.94

Genetic literature · overall 0.67

megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 20.87

Genetic literature · overall 0.80

schizophrenia0.74

Genetic · overall 0.46

risk-taking behaviour0.67

Genetic · overall 0.41

glioma0.64

Genetic · overall 0.44

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

breast cancer0.90

Clinical · overall 0.57

neoplasm0.64

Clinical · overall 0.45

cancer0.18

Clinical · overall 0.41

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 10.47

Genetic literature

overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes0.46

Genetic literature

Show all associations
megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 20.80
Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus0.67
breast cancer0.57
megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 10.47
schizophrenia0.46
overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes0.46
neoplasm0.45
glioma0.44
risk-taking behaviour0.41
cancer0.41

Open Targets ranks 1,141 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 13 total

XL-418Phase 1

neoplasm

MK-2206Phase 2

rectum adenocarcinoma · neuroendocrine neoplasm · colorectal cancer

UPROSERTIBPhase 2

colorectal cancer · lymphoma · acute myeloid leukemia

RUPITASERTIBPhase 1

breast cancer · neoplasm

CAPIVASERTIBApproval

breast cancer · breast neoplasm · neoplasm

MIRANSERTIBPhase 2

Proteus syndrome · pik3ca related overgrowth spectrum · PIK3CA-related overgrowth spectrum

TAS0612Phase 1
LY-2780301Phase 1 2

breast cancer

AFURESERTIBPhase 3

breast cancer · childhood leukemia · Langerhans cell histiocytosis

IPATASERTIBPhase 3

breast cancer · colorectal cancer · prostate cancer

Tractability

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

Safety liabilities

heart diseaseregulation of catalytic activity

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.

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial Testing Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients With Asymptomatic or Mildly Symptomatic, Previously Untreated, Metastatic Castrate-Resistant Prostate CancerPHASE3

COMPLETED · via ipatasertib · NCT03072238

A Phase Ib, Open-Label, Multicenter Study Evaluating The Safety, Efficacy and Pharmacokinetics Of Ipatasertib In Combination With Atezolizumab And Docetaxel In Metastatic Castration-Resistant Prostate Cancer.PHASE1

TERMINATED · via ipatasertib · NCT04404140

A Phase III Double-blind Randomised Study Assessing the Efficacy and Safety of Capivasertib + Fulvestrant Versus Placebo + Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Breast Cancer Following Recurrence or Progression On or After Treatment With an Aromatase InhibitorPHASE3

ACTIVE_NOT_RECRUITING · via capivasertib · NCT04305496

A Phase 1b/2 Trial Investigating the Safety and Efficacy of Oral AMXT 1501 and Oral DFMO in Combination With Standard of Care in Patients With Advanced Solid Tumors Who Progressed After Prior TherapiesPHASE1/PHASE2

RECRUITING · via capivasertib · NCT07287917

An Open-label, Fixed Sequence Study in Healthy Subjects to Assess the Pharmacokinetics of Capivasertib When Administered Alone and In Combination With ItraconazolePHASE1

COMPLETED · via capivasertib · NCT04712396

A Phase 1 Open-Label, Dose-Escalation and Dose-Expansion Study to Investigate the Safety, Pharmacokinetics, and Anti-Tumor Activity of IACS-6274 as Monotherapy and in Combination in Patients With Advanced Solid TumorsPHASE1

RECRUITING · via capivasertib · NCT05039801

Show remaining trials (24)
A Phase IB and Randomized Phase II Trial of Megestrol Acetate With or Without Ipatasertib in Recurrent or Metastatic Endometrioid Endometrial CancerPHASE1/PHASE2

ACTIVE_NOT_RECRUITING · via ipatasertib · NCT05538897

A Phase II Randomized, Double-Blind, Study of Ipatasertib (GDC-0068), an Inhibitor to AKT, in Combination With Paclitaxel as Neoadjuvant Treatment for Patients With Early Stage Triple Negative Breast CancerPHASE2

COMPLETED · via ipatasertib · NCT02301988

A Randomized Phase II Study Comparing Single-Agent Olaparib, Single Agent Cediranib, and the Combinations of Cediranib/Olaparib, Olaparib/Durvalumab (MEDI4736), Cediranib/Durvalumab (MEDI4736), Olaparib/AZD5363 (Capivasertib) in Women With Recurrent, Persistent or Metastatic Endometrial Cancer.: A Platform Trial for Women With Recurrent or Persistent Endometrial CancerPHASE2

ACTIVE_NOT_RECRUITING · via capivasertib · NCT03660826

The Rome Trial From Histology to Target: the Road to Personalize Target Therapy and ImmunotherapyPHASE2

UNKNOWN · via ipatasertib · NCT04591431

A Phase IIIB Study to Evaluate the Use of Capivasertib in Combination With Fulvestrant in Patients With HR+ / HER2- Advanced Breast Cancer Who Have Relapsed/Progressed on ET and CDK4/6 Inhibitor Reflecting Real World Clinical Practice in SpainPHASE3

ACTIVE_NOT_RECRUITING · via capivasertib · NCT06764186

A Phase Ib, Open-label, Dose-escalation Study of the Safety and Pharmacology of Ipatasertib (GDC-0068) in Combination With Docetaxel, Fluoropyrimidine Plus Oxaliplatin, Paclitaxel, or Enzalutamide in Patients With Advanced Solid TumorsPHASE1

COMPLETED · via ipatasertib · NCT01362374

Molecular Analysis for Therapy Choice (MATCH)PHASE2

ACTIVE_NOT_RECRUITING · via capivasertib · NCT02465060

A Single Arm, Phase I/II Trial of Neoadjuvant Androgen Deprivation, Darolutamide, and Ipatasertib in Men With Localized, High Risk Prostate Cancer Big Ten Cancer Research Consortium BTCRC-GU19-404PHASE1/PHASE2

TERMINATED · via ipatasertib · NCT04737109

CApivasertib, Venetoclax And Low-intensity chemotheRapY for Adults With ALL/LBLPHASE1/PHASE2

RECRUITING · via capivasertib · NCT07294677

A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Hormone Receptor-Positive HER2-Negative Breast Cancer (MORPHEUS-HR+ Breast Cancer)PHASE1/PHASE2

COMPLETED · via ipatasertib · NCT03280563

A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Breast Cancer (MORPHEUS-BREAST CANCER)PHASE1/PHASE2

RECRUITING · via ipatasertib · NCT04802759

Phase 1/1b Study of AKT Inhibitor Ipatasertib With Chemoradiation for Locally Advanced Head and Neck CancerPHASE1

RECRUITING · via ipatasertib · NCT05172245

A Phase 1b Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination With Other Anti-cancer Agents in Patients With Metastatic HER2-low Breast Cancer (DESTINY-Breast08)PHASE1

ACTIVE_NOT_RECRUITING · via capivasertib · NCT04556773

A Phase II Study Investigating Preoperative Combination Strategies for Immunotherapy in Patients With Untreated, Operable ER+, HER2-negative Primary Breast CancerPHASE2

COMPLETED · via ipatasertib · NCT03395899

CaptAin - Effect of Capivasertib on ctDNA in ER Positive Breast CancerPHASE2

WITHDRAWN · via capivasertib · NCT06613516

An Open-label, Fixed-sequence Study to Assess the Effect of Capivasertib on the Pharmacokinetics of Oral Rosuvastatin (a BCRP, OATP1B1 and OATP1B3 Sensitive Substrate) in Healthy ParticipantsPHASE1

COMPLETED · via capivasertib · NCT07088913

Precision Neoadjuvant Therapy for High Risk Localized Prostate Cancer With PTEN LossPHASE2

RECRUITING · via capivasertib · NCT05593497

A Phase IIIb Single Arm, 2 Cohorts Study Assessing the Efficacy and Safety of Capivasertib+ Fulvestrant as Treatment for Locally Advanced(Inoperable) or Metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Breast Cancer Following Recurrence or Progression On or After Treatment With Endocrine Therapy in Chinese PatientsPHASE3

ACTIVE_NOT_RECRUITING · via capivasertib · NCT06635447

A Phase 1b/2, Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Patients With Metastatic Breast CancerPHASE1/PHASE2

ACTIVE_NOT_RECRUITING · via capivasertib · NCT05563220

Continuous ReAssessment With Flexible ExTension in Rare Malignancies - CRAFT: The NCT-PMO-1602 Phase II TrialPHASE2

COMPLETED · via ipatasertib · NCT04551521

Randomised Open-label Phase II Study of Induction Standard of Care Fulvestrant and CDK4/6 Inhibition With the Addition of Ipatasertib in Metastatic ER+/HER2- Breast Cancer Patients Without ctDNA SuppressionPHASE2

ACTIVE_NOT_RECRUITING · via ipatasertib · NCT04920708

A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating The Efficacy And Safety Of Multiple Immunotherapy-Based Treatment Combinations In Patients With Metastatic Non-Small Cell Lung Cancer (Morpheus-Lung)PHASE1/PHASE2

TERMINATED · via ipatasertib · NCT03337698

A Phase 1, Single-Dose, Randomized, Cross-Over, Relative Bioavailability, and Food Effect Study of Ipatasertib (GDC-0068) in Healthy SubjectsPHASE1

COMPLETED · via ipatasertib · NCT02536391

A Phase I/IB Study of Ipatasertib in Combination With Carboplatin, Carboplatin/Paclitaxel, or Capecitabine/Atezolizumab in Patients With Metastatic Triple Negative Breast CancerPHASE1/PHASE2

COMPLETED · via ipatasertib · NCT03853707

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2Well supported
0.94
agreement 0.84–1.00
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 0.68–0.94
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 0.62–0.89
Genetic91%Literature9%

Open Targets aggregate 0.46 · 2 independent evidence families

gliomaModerately supported
0.72
agreement 0.61–0.83
Genetic72%Somatic mutation22%Literature5%

Open Targets aggregate 0.44 · 3 independent evidence families

breast cancerModerately supported
0.70
agreement 0.55–0.86
Clinical88%Literature12%

Open Targets aggregate 0.57 · 2 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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

13

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  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 publication2024-03-13
    Endocrine and Targeted Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer-Capivasertib-Fulvestrant: ASCO Rapid Recommendation Update.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024 · 36 citations · Europe PMC · via capivasertib

  9. 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

  10. Regulatory approval2023-11-16

    Approval: CAPIVASERTIB (NDA218197)

    fda · regulatory · fda · via capivasertib

  11. 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

  12. 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

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.