MAP2K1 mitogen-activated protein kinase kinase 1
ENSG00000169032 · protein coding · Open Targets profile
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126). Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis. {ECO:0000269|PubMed:14737111, ECO:0000269|PubMed:17101779, ECO:0000269|PubMed:29433126}.
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 Withdrawn means the drug was pulled from the market or from development.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, Human Protein Atlas loc
- PROTAC
- Literature, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.34521999955177307 (upper bound 0.5243300199508667). 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 393 registry trials, updated in the last three years, of the most advanced drugs against MAP2K1 (mirdametinib, trametinib dimethyl sulfoxide, cobimetinib, selumetinib, binimetinib, trametinib, refametinib, avutometinib, pimasertib, CI-1040, E-6201, TAK-733), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Rachel GrishamGOG Foundation · 4 of 4 trials Phase 2+
- Alan L HoMemorial Sloan Kettering Cancer Center · 3 of 3 trials Phase 2+
- Hussein A TawbiM.D. Anderson Cancer Center · 3 of 3 trials Phase 2+Ph2NCT03175432 · Bevacizumab and Atezolizumab With or Without Cobimetinib in Treating Patients With Untreated Melanoma Brain Metastasesbrief
- Jason J LukeECOG-ACRIN Cancer Research Group · 3 of 3 trials Phase 2+
- Matthew KrebsThe Christie Hospital · 3 of 3 trials Phase 2+Ph2/Ph3NCT07440290 · DETERMINE Trial Treatment Arm 07: Dabrafenib in Combination With Trametinib in Adult, Paediatric and Teenage/Young Adult Patients With BRAF V600 Mutation-Positive Cancers.brief
- Ryan J SullivanMassachusetts General Hospital · 2 of 3 trials Phase 2+
- Brigitte C WidemannNational Cancer Institute (NCI) · 2 of 2 trials Phase 2+
- Carl E AllenBaylor College of Medicine · 2 of 2 trials Phase 2+
- Christine ParseghianM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
- F OpdamThe Netherlands Cancer Institute · 2 of 2 trials Phase 2+
- Georgina LongMelanoma Institute Australia · 2 of 2 trials Phase 2+
- Jason R FangusaroPediatric Brain Tumor Consortium · 2 of 2 trials Phase 2+
- Nilofer S AzadJHU Sidney Kimmel Comprehensive Cancer Center LAO · 2 of 2 trials Phase 2+
- Paolo AsciertoFondazione Melanoma Onlus · 2 of 2 trials Phase 2+
- Robert J KreitmanNational Cancer Institute (NCI) · 2 of 2 trials Phase 2+
Registry trials of mirdametinib, trametinib dimethyl sulfoxide, cobimetinib, selumetinib, binimetinib, trametinib, refametinib, avutometinib, pimasertib, CI-1040, E-6201, TAK-733 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; 285 of 383 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.
154 trials of drugs against MAP2K1 were stopped early; 8 give no reason
Terminated, withdrawn and suspended interventional trials of mirdametinib, trametinib dimethyl sulfoxide, cobimetinib, selumetinib, binimetinib, trametinib, refametinib, avutometinib, pimasertib, CI-1040, E-6201, TAK-733, 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 154.
- suspended · 2026-11-10 · National Cancer Institute (NCI) · Mirdametinib“Administrative hold pending non-safety related changes to the study design.”
- terminated · 2026-10-21 · Novartis Pharmaceuticals · trametinib“Business reasons and not based on any safety concerns.”
- suspended · 2026-10-15 · City of Hope Medical Center · Trametinib“Accrual goal met”
- terminated · 2026-10-06 · ECOG-ACRIN Cancer Research Group · Trametinib dimethyl sulfoxide“Slow accrual”
- terminated · 2026-10-06 · ECOG-ACRIN Cancer Research Group · Binimetinib“Slow accrual”
- terminated · 2026-08-20 · SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany · Mirdametinib 2mg, Mirdametinib 3mg, Mirdametinib 4mg“Lack of tolerability of BGB-3245 (Brimarafenib) when given in combination with Mirdametinib”
- terminated · 2026-08-03 · Hoffmann-La Roche · Cobimetinib“The study was closed because the sponsor decided not to continue the development of certain treatment combinations.”
- terminated · 2026-07-22 · M.D. Anderson Cancer Center · Trametinib“<75% participation”
- terminated · 2026-06-04 · Pfizer · binimetinib“The study was prematurely discontinued due to strategic reasons. The PF-07284892 program will continue”
- withdrawn · 2026-05-22 · University Health Network, Toronto · Trametinib tablet“No patients enrolled”
- terminated · 2026-05-14 · University of Utah · Trametinib“Lack of Funding”
- terminated · 2026-05-12 · Hoffmann-La Roche · Cobimetinib“Study was closed early as the sponsor decided not to continue development of certain treatment combinations.”
- suspended · 2026-05-08 · University of Chicago · VS-6766/avutometinib“enrollment goal met pending determination of evaluable subjects”
- withdrawn · 2026-04-21 · SRH Wald-Klinikum Gera GmbH · Encorafenib & Binimetinib Treatment“The study was terminated early due to insufficient patient recruitment.”
- terminated · 2026-04-13 · Cancer Trials Ireland · Trametinib“Study terminated due to futility”
- terminated · 2026-04-08 · Deciphera Pharmaceuticals, LLC · Trametinib, Binimetinib“Trial terminated due to business decision, not based on any safety or efficacy concerns.”
- terminated · 2026-03-18 · M.D. Anderson Cancer Center · Pimasertib“Insufficient accrual”
- terminated · 2026-03-09 · Pfizer · binimetinib“Study terminated due to inability to recruit the target number of patients. There were no safety and/or efficacy concerns involved in the decision to stop enrollment.”
- terminated · 2026-03-03 · National Cancer Institute (NCI) · Binimetinib“Other - slow accrual”
- terminated · 2026-02-25 · Gordon Mills, MD, PhD · Selumetinib“loss of funding”
- terminated · 2026-01-09 · Pfizer · Binimetinib“Study was terminated due to portfolio re-prioritization and strategic considerations. The decision was not based on any safety concerns and/or regulatory interactions”
- terminated · 2025-12-24 · Novartis Pharmaceuticals · Trametinib“The decision of early termination was made due to business reasons, and was not based on any safety concerns for any of the treatment combinations.”
- terminated · 2025-10-23 · Pfizer · Binimetinib“Pfizer has made an internal business decision to not continue further development of PF-07284890. This decision was not due to major safety concerns or requests from any regulatory authorities.”
- terminated · 2025-09-18 · Novartis Pharmaceuticals · Trametinib“Sponsor decision”
- terminated · 2025-08-19 · Mayo Clinic · matched by the registry's drug synonyms“Financial issues”
Paediatric incentives and obligations for MAP2K1's drugs
For mirdametinib, trametinib dimethyl sulfoxide, cobimetinib, selumetinib, binimetinib, trametinib, refametinib, avutometinib, pimasertib, CI-1040, E-6201, TAK-733: 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: yes · MAP2K1 is on the list. Membership alone neither requires nor waives a pediatric study.Rule: 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 · EMA/PE/0000245064 (avutometinib;defactinib, Treatment of ovarian cancer): W: decision granting a waiver in all age groups for all conditions or indications, 13 Jun 2025; EMEA-003525-PIP01-23 (mirdametinib, Treatment of neurofibromatosis type 1): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 20 Jun 2024; EMEA-001585-PIP01-13-M06 (selumetinib, Treatment of melanoma;Treatment of neurofibromatosis type 1;Treatment of thyroid cancer): PM: decision on the application for modification of an agreed PIP, 25 Apr 2024; compliance positive 18 Oct 2024; EMEA-001454-PIP06-23 (binimetinib, Treatment of lung cancer): W: decision granting a waiver in all age groups for all conditions or indications, 8 Sept 2023; +5 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/3/25/3090 positive 18 Jul 2025: Treatment of ovarian cancer; EU/3/19/2184 positive 25 Jul 2019: Treatment of neurofibromatosis type 1; EU/3/23/2870 positive 13 Dec 2023: Treatment of amyotrophic lateral sclerosis; EU/3/23/2865 positive 13 Dec 2023: Treatment of glioma; +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: yes · Koselugo: authorised since 17 Jun 2021, orphan medicine, conditional; Ezmekly: authorised since 17 Jul 2025, orphan medicine, conditional; Mekinist: authorised since 30 Jun 2014; Spexotras: authorised since 5 Jan 2024, orphan medicine; +3 moreRule: 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: yes · Mirdametinib [Gomekli], 11 Feb 2025: Treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection; Selumetinib [Koselugo], 19 Nov 2025: Treatment of adult and pediatric patients 1 year of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN); Trametinib [Mekinist], 31 Aug 2023: In combination with dabrafenib, for the treatment of adult and pediatric patients 1 year of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options; +1 moreRule: 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 · 98 interventional studies of mirdametinib, trametinib dimethyl sulfoxide, cobimetinib, selumetinib, binimetinib, trametinib, refametinib, avutometinib, pimasertib, ci-1040, e-6201, tak-733 include patients under 18; 66 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 19 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.