PRKCB protein kinase C beta
ENSG00000166501 · protein coding · Open Targets profile
Calcium-activated, phospholipid- and diacylglycerol (DAG)- dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR- induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity (PubMed:11598012). Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A (PubMed:20228790). In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1 (PubMed:25982116). Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis (By similarity). Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (PubMed:19176525). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). Acts as a regulator of dopamine signaling by mediating constitutive phosphorylation of dopamine receptors DRD1 and DRD2, inhibiting G protein-coupled receptor signaling (PubMed:20969574). {ECO:0000250|UniProtKB:P68404, ECO:0000269|PubMed:11598012, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:20969574, ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:25982116, ECO:0000269|PubMed:36040231}.
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, High-Quality Ligand, Druggable Family
- Antibody
- GO CC high conf, UniProt loc med conf
- PROTAC
- Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.15952999889850616 (upper bound 0.25363001227378845). 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 27 registry trials, updated in the last three years, of the most advanced drugs against PRKCB (midostaurin, enzastaurin, ruboxistaurin, UCN-01, sotrastaurin), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Christian RECHER+33 5 31 15 63 55 · 1 of 1 trials Phase 2+
- Christoph RölligTechnische Universität Dresden, Medical Faculty Carl Gustav Carus · 1 of 1 trials Phase 2+
- Christoph RummeltUniversity Hospital Freiburg · 1 of 1 trials Phase 2+
- Gerwin HulsUMCG / HOVON · 1 of 1 trials Phase 2+
- Ido Didi FabianSheba Medical Center · 1 of 1 trials Phase 2+
- Laura C MichaelisSWOG Cancer Research Network · 1 of 1 trials Phase 2+
- M. RaaijmakersErasmus MC / HOVON · 1 of 1 trials Phase 2+Ph3NCT04027309 · A Study of Gilteritinib Versus Midostaurin in Combination With Induction and Consolidation Therapy Followed by One-year Maintenance in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndromes With Excess Blasts-2 With FLT3 Mutations Eligible for Intensive Chemotherapybrief
- Meagan JacobyWashington University School of Medicine · 1 of 1 trials Phase 2+
- Richard M. StoneDana-Farber Cancer Institute · 1 of 1 trials Phase 2+
- Selena LugerUniversity of Pennsylvania · 1 of 1 trials Phase 2+
- Shaine MorrisTexas Children's Hospital and Baylor College of Medicine · 1 of 1 trials Phase 2+
- Sherene ShalhubUniversity of Washington · 1 of 1 trials Phase 2+
- Tapan M KadiaM.D. Anderson Cancer Center · 1 of 1 trials Phase 2+
- Vijaya R BhattUniversity of Nebraska · 1 of 1 trials Phase 2+
- Rafael BejarAptose Biosciences Inc. · 0 of 1 trials Phase 2+
Registry trials of midostaurin, enzastaurin, ruboxistaurin, UCN-01, sotrastaurin 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; 17 of 25 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. 2 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
29 trials of drugs against PRKCB were stopped early; 6 give no reason
Terminated, withdrawn and suspended interventional trials of midostaurin, enzastaurin, ruboxistaurin, UCN-01, sotrastaurin, CEP-2563, GSK-690693, 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 29.
- terminated · 2025-03-07 · Aptose Biosciences Inc. · matched by the registry's drug synonyms“Change in corporate strategy”
- terminated · 2025-02-25 · Niguarda Hospital · Midostaurin“didn't reach the primary endpoint”
- withdrawn · 2024-10-01 · Guenther Koehne · Midostaurin“Could not accrue”
- suspended · 2024-03-08 · Aytu BioPharma, Inc. · Enzastaurin“Indefinite hold by company”
- terminated · 2022-10-06 · Insel Gruppe AG, University Hospital Bern · Midostaurin“Insufficient recruitment”
- withdrawn · 2022-06-06 · University of Tennessee · Ruboxistaurin“No funding”
- withdrawn · 2022-05-25 · University Hospital Heidelberg · matched by the registry's drug synonyms“Study turned out no longer feasible”
- terminated · 2022-01-21 · University of Jena · Midostaurin“Insufficient Recruitment”
- terminated · 2020-12-19 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“Study terminated due to enrolment challenges and availability of other options for DLBCL patients. The termination is not a consequence of any safety concern.”
- terminated · 2020-12-17 · Novartis Pharmaceuticals · matched by the registry's drug synonymsNo reason given
- terminated · 2020-11-05 · Eli Lilly and Company · enzastaurin“Terminated due to lack of efficacy demonstrated in relevant participant population in other clinical trials.”
- terminated · 2020-09-24 · Eli Lilly and Company · Enzastaurin“Study has been terminated due to slow enrollment”
- terminated · 2020-09-16 · Array Biopharma, now a wholly owned subsidiary of Pfizer · matched by the registry's drug synonyms“The trial was terminated for scientific reasons.”
- terminated · 2020-08-10 · Eli Lilly and Company · enzastaurin“Lack of efficacy”
- withdrawn · 2020-01-09 · Novartis Pharmaceuticals · midostaurin“It was determined that the study design may not be optimal given the changing AML treatment landscape.”
- terminated · 2019-12-05 · National Cancer Institute (NCI) · Enzastaurin (LY317615) monohydronchlorideNo reason given
- terminated · 2019-08-07 · Mayo Clinic · MidostaurinNo reason given
- withdrawn · 2018-10-22 · University of Florida · Midostaurin“Insufficient funding”
- terminated · 2018-09-27 · David Iberri · Midostaurin“Accrual factor”
- withdrawn · 2018-05-04 · Stanford University · Midostaurin“Logistical and administrative issues”
- terminated · 2017-05-15 · National Cancer Institute (NCI) · UCN-01 (7-hydroxystaurosporine)“IND was withdrawn by CTEP due to low accrual and cost of maintaining the IND.”
- withdrawn · 2017-04-05 · James Blachly · sotrastaurin acetate“Decision made by the Principal Investigator”
- terminated · 2017-01-18 · GlaxoSmithKline · matched by the registry's drug synonymsNo reason given
- terminated · 2015-12-22 · Novartis Pharmaceuticals · midostaurin“Despite considerable efforts to boost recruitment during the final year of the study, no new patients were enrolled.”
- withdrawn · 2015-10-08 · Eastern Cooperative Oncology Group · enzastaurin hydrochloride“ECOG will not proceed with activation”
Paediatric incentives and obligations for PRKCB's drugs
For midostaurin, enzastaurin, ruboxistaurin, UCN-01, sotrastaurin, CEP-2563, GSK-690693: 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 · PRKCB 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: yes · EMEA-000780-PIP01-09-M08 (Midostaurin, Treatment of acute myeloid leukaemia;Treatment of malignant mastocytosis;Treatment of mast cell leukaemia): PM: decision on the application for modification of an agreed PIP, 16 Aug 2024; EMEA-003096-PIP02-22 (enzastaurin hydrochloride, Treatment of Ehlers-Danlos Syndrome): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 30 Dec 2023; EMEA-000093-PIP02-10 (sotrastaurin acetate, Prevention of rejection of transplanted kidney): W: decision granting a waiver in all age groups for all conditions or indications, 26 Jan 2011; EMEA-000093-PIP01-07-M01 (sotrastaurin acetate, Treatment of chronic plaque psoriasis): PM: decision on the application for modification of an agreed PIP, 4 Jul 2011; +1 moreRule: 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/3/05/343 withdrawn 27 May 2024: Treatment of glioma; EU/3/22/2582 withdrawn 24 Feb 2022: Treatment of Ehlers-Danlos syndrome; EU/3/07/442 withdrawn 20 Mar 2007: Treatment of diffuse large B-cell lymphoma; EU/3/10/765 positive 4 Aug 2010: Treatment of mastocytosis; +1 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: yes · Rydapt: authorised since 18 Sept 2017, orphan medicine; Arxxant: application withdrawnRule: 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 midostaurin, enzastaurin, ruboxistaurin, ucn-01, sotrastaurin, cep-2563, gsk-690693Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 7 interventional studies of midostaurin, enzastaurin, ruboxistaurin, ucn-01, sotrastaurin, cep-2563, gsk-690693 include patients under 18; 1 is 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, 2026-11-12
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 7 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.