GSK3B glycogen synthase kinase 3 beta
ENSG00000082701 · protein coding · Open Targets profile
Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1 (PubMed:11430833, PubMed:12554650, PubMed:14690523, PubMed:16484495, PubMed:1846781, PubMed:20937854, PubMed:9072970). Requires primed phosphorylation of the majority of its substrates (PubMed:11430833, PubMed:16484495). In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:8397507). May also mediate the development of insulin resistance by regulating activation of transcription factors (PubMed:8397507). Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase (PubMed:8397507). In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes (PubMed:12554650). Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA (PubMed:1846781). Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin (PubMed:9072970). Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules (PubMed:14690523). MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease (PubMed:14690523). Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854). Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair (By similarity). Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti- apoptotic response to TNF (TNF/TNFA) (By similarity). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes (By similarity). Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (By similarity). Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin (PubMed:9819408). Is necessary for the establishment of neuronal polarity and axon outgrowth (PubMed:20067585). Phosphorylates MARK2, leading to inhibition of its activity (By similarity). Phosphorylates SIK1 at 'Thr-182', leading to sustainment of its activity (PubMed:18348280). Phosphorylates ZC3HAV1 which enhances its antiviral activity (PubMed:22514281). Phosphorylates SNAI1, leading to its ubiquitination and proteasomal degradation (PubMed:15448698, PubMed:15647282, PubMed:25827072, PubMed:29059170). Phosphorylates SFPQ at 'Thr-687' upon T-cell activation (PubMed:20932480). Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including BMAL1, CLOCK and PER2 (PubMed:19946213, PubMed:28903391). Phosphorylates FBXL2 at 'Thr-404' and primes it for ubiquitination by the SCF(FBXO3) complex and proteasomal degradation (By similarity). Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation (PubMed:19946213). Phosphorylates BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation (PubMed:28903391). Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation (PubMed:24391509). Regulates the circadian rhythmicity of hippocampal long-term potentiation and BMAL1 and PER2 expression (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, activating KAT5/TIP60 acetyltransferase activity and promoting acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (PubMed:18846110). Phosphorylates E2F1, promoting the interaction between E2F1 and USP11, stabilizing E2F1 and promoting its activity (PubMed:17050006, PubMed:28992046). Phosphorylates mTORC2 complex component RICTOR at 'Ser-1235' in response to endoplasmic stress, inhibiting mTORC2 (PubMed:21343617). Phosphorylates mTORC2 complex component RICTOR at 'Thr-1695' which facilitates FBXW7-mediated ubiquitination and subsequent degradation of RICTOR (PubMed:25897075). Acts as a negative regulator of smoothened signaling by mediating phosphorylation of GLI2 and GLI3 in absence of smoothened, promoting their processing by the SCF(BTRC) complex (PubMed:16705181). Phosphorylates FXR1, promoting FXR1 ubiquitination by the SCF(FBXO4) complex and FXR1 degradation by the proteasome (By similarity). Phosphorylates interleukin-22 receptor subunit IL22RA1, preventing its proteasomal degradation (By similarity). Phosphorylates and inhibits the CTP synthase and protein-asparagine deamidase activities of CTPS1 (PubMed:17681942). Phosphorylates DSP at multiple sequential serine residues in the C-terminus tail, promoting its recruitment to developing desmosome cell-cell junctions (PubMed:25733715). {ECO:0000250|UniProtKB:P18266, ECO:0000250|UniProtKB:Q9WV60, ECO:0000269|PubMed:11430833, ECO:0000269|PubMed:12554650, ECO:0000269|PubMed:14690523, ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:16484495, ECO:0000269|PubMed:16705181, ECO:0000269|PubMed:17050006, ECO:0000269|PubMed:17681942, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:1846781, ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:19946213, ECO:0000269|PubMed:20067585, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:21343617, ECO:0000269|PubMed:22514281, ECO:0000269|PubMed:24391509, ECO:0000269|PubMed:25733715, ECO:0000269|PubMed:25827072, ECO:0000269|PubMed:25897075, ECO:0000269|PubMed:28903391, ECO:0000269|PubMed:28992046, ECO:0000269|PubMed:29059170, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:8397507, ECO:0000269|PubMed:9072970, ECO:0000269|PubMed:9819408}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf
- PROTAC
- Literature, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.26583999395370483 (upper bound 0.4093500077724457). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 138 registry trials, updated in the last three years, of the most advanced drugs against GSK3B (lithium, lithium carbonate, tideglusib, LY-2090314, elraglusib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Thomas GuttusoUniversity at Buffalo · 2 of 2 trials Phase 2+
- Polyxeni GeorgilaPrivate Practice · 1 of 2 trials Phase 2+
- Aglaia VignoliUniversity of Milan · 1 of 1 trials Phase 2+
- Annemarie HübersUniversity Hospital, Geneva · 1 of 1 trials Phase 2+
- Aristotle VoineskosCentre for Addiction and Mental Health · 1 of 1 trials Phase 2+
- Barry F ChaitinUniversity of California, Irvine · 1 of 1 trials Phase 2+
- Christopher MorrowJohns Hopkins University · 1 of 1 trials Phase 2+
- Claire O'DonovanQueen Elizabeth II Health Sciences Centre, CDHA · 1 of 1 trials Phase 2+
- Colin D WeekesMassachusetts General Hospital · 1 of 1 trials Phase 2+
- DECHANET AlineAssistance Publique - Hôpitaux de Paris (AP-HP) · 1 of 1 trials Phase 2+
- Delorme RichardAPHP · 1 of 1 trials Phase 2+
- Diane NamSunnybrook Health Sciences Centre · 1 of 1 trials Phase 2+
- DP DevanandColumbia University · 1 of 1 trials Phase 2+
- Edward HueyBrown University · 1 of 1 trials Phase 2+
- Eric LenzeWashington University School of Medicine · 1 of 1 trials Phase 2+
Registry trials of lithium, lithium carbonate, tideglusib, LY-2090314, elraglusib updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 117 of 128 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 10 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
47 trials of drugs against GSK3B were stopped early; 5 give no reason
Terminated, withdrawn and suspended interventional trials of lithium, lithium carbonate, tideglusib, LY-2090314, elraglusib, AZD-1080, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 47.
- terminated · 2026-11-05 · Dr. Inge Winter · Lithium“The site in Israel stopped recruitment due to logistic reasons. Other sites are recruiting for 2023-506602-39-00, 2023-506605-19-00, 2023-506617-21-00.”
- terminated · 2026-05-13 · Stichting TRICALS Foundation · Lithium Carbonate 400 MG“The planned interim analysis showed no survival benefit of taking the drug when compared with placebo.”
- terminated · 2025-10-23 · Ivoclar Vivadent AG · matched by the registry's drug synonyms“Material did not perform accordingly in other clinical trials.”
- terminated · 2025-09-25 · Negovsky Reanimatology Research Institute · Lithium Carbonate“Decision of the local ethics committee”
- terminated · 2025-07-08 · Cancer Trials Ireland · Lithium“Poor accrual and the field has moved on.”
- terminated · 2025-03-25 · University Hospital, Montpellier · matched by the registry's drug synonyms“no more inclusion”
- withdrawn · 2024-09-19 · Nova Scotia Health Authority · Lithium“recruitment difficulties”
- terminated · 2024-07-25 · University of Michigan · matched by the registry's drug synonyms“Loss of funding due to COVID-19”
- terminated · 2024-04-29 · VA Office of Research and Development · Lithium“terminated early due to non-safety related DMC recommendations”
- terminated · 2023-04-13 · University of Michigan · matched by the registry's drug synonyms“COVID, loss of funding”
- withdrawn · 2023-03-01 · Yale University · Ketamine/Lithium“No funding”
- withdrawn · 2021-10-08 · University of British Columbia · matched by the registry's drug synonyms“Unable to recruit participants”
- terminated · 2021-08-12 · University of Michigan · matched by the registry's drug synonyms“COVID shutdown”
- terminated · 2021-01-29 · Nova Scotia Health Authority · lithium“Recruitment difficulties”
- terminated · 2020-07-10 · Keming Gao · Lithium“Lack of funding”
- terminated · 2020-03-25 · Institut Cancerologie de l'Ouest · matched by the registry's drug synonyms“The study stopped due to a death in the arm control”
- terminated · 2020-01-10 · Aziende Chimiche Riunite Angelini Francesco S.p.A · Lithium sulphate prolonged-release 660 mg, Lithium carbonate immediate-release 150 mg and 300 mg“Sponsor's decision due to slow enrollment rate.”
- terminated · 2019-12-09 · University of Wisconsin, Madison · Lithium carbonate“Budget/Funding”
- withdrawn · 2019-04-01 · Smith & Nephew, Inc. · matched by the registry's drug synonyms“Business decision”
- terminated · 2019-01-15 · Eli Lilly and Company · matched by the registry's drug synonyms“Study has been terminated due to slow enrollment.”
- withdrawn · 2018-08-16 · William V. Bobo, M.D. · Lithium“Principal Investigator moved to Jacksonville, FL campus.”
- terminated · 2018-02-28 · Hannover Medical School · LithiumNo reason given
- withdrawn · 2018-02-09 · Ewha Womans University · Lithium“The research project has been cancelled before any participants were enrolled.”
- terminated · 2017-08-16 · University Hospitals Cleveland Medical Center · Lithium“Ran out of funding”
- terminated · 2017-05-09 · Massachusetts General Hospital · matched by the registry's drug synonyms“Lack of enrollment”
Paediatric incentives and obligations for GSK3B's drugs
For lithium, lithium carbonate, tideglusib, LY-2090314, elraglusib, AZD-1080: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · GSK3B is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: no · No EMA paediatric investigation plan decision names lithium, lithium carbonate, tideglusib, ly-2090314, elraglusib, azd-1080Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/24/3016 positive 16 Jan 2025: Treatment of soft tissue sarcoma; EU/3/24/3015 positive 16 Jan 2025: Treatment of pancreatic cancer; EU/3/23/2822 positive 16 Aug 2023: Treatment of Kleine Levin syndrome; EU/3/22/2674 positive 10 Aug 2022: Treatment of familial adenomatous polyposis (FAP); +2 moreRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: no · EMA lists no centrally authorised medicine of lithium, lithium carbonate, tideglusib, ly-2090314, elraglusib, azd-1080Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of lithium, lithium carbonate, tideglusib, ly-2090314, elraglusib, azd-1080Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 61 interventional studies of lithium, lithium carbonate, tideglusib, ly-2090314, elraglusib, azd-1080 include patients under 18; 13 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 6 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.