Live from Open Targets Platform, fetched 2026-11-11 16:02 UTC. Every row links to its source record.

MAPK1 mitogen-activated protein kinase 1

ENSG00000100030 · protein coding · Open Targets profile

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the 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. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1 and FXR1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2, GLI1 or GRB10) (PubMed:35831023). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in response to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity). Phosphorylates phosphoglycerate kinase PGK1 under hypoxic conditions to promote its targeting to the mitochondrion and suppress the formation of acetyl-coenzyme A from pyruvate (PubMed:26942675). Phosphorylates GJA1 at 'Ser-279' and 'Ser- 282' resulting in an increase in GJA1 ubiquitination and ultimately lysosomal degradation (By similarity). Acts as a positive regulator of smoothened signaling by mediating phosphorylation of GLI1 in response to smoothened activation, promoting its dissociation from SUFU inhibitor and translocation to the nucleus (PubMed:35831023). {ECO:0000250|UniProtKB:P63086, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:10637505, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12792650, ECO:0000269|PubMed:12794087, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15184391, ECO:0000269|PubMed:15241487, ECO:0000269|PubMed:15616583, ECO:0000269|PubMed:15664191, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19879846, ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:32721402, ECO:0000269|PubMed:35831023, ECO:0000269|PubMed:7588608, ECO:0000269|PubMed:8622688, ECO:0000269|PubMed:9480836, ECO:0000269|PubMed:9596579, ECO:0000269|PubMed:9649500, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:15526160, ECO:0000303|PubMed:16393692, ECO:0000303|PubMed:19565474, ECO:0000303|PubMed:21779493}.

None of the 6 drugs recorded against MAPK1 is approved yet

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.

In 15 of 15 cancers, the evidence for MAPK1 comes mainly from mutations found in tumours

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.

Inherited (germline) variantsMutations in tumours (somatic)

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: Advanced Clinical, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
Antibody: GO CC high conf
PROTAC: Literature, UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder

gnomAD loss of function constraint: o/e 0.2523899972438812 (upper bound 0.42809998989105225). 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 13 registry trials, updated in the last three years, of the most advanced drugs against MAPK1 (ulixertinib, temuterkib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.

Donald W Parsons
Children's Oncology Group · 1 of 1 trials Phase 2+
Ph2NCT03155620 · Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)brief
Eli Diamond
Memorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
Ph2NCT06411821 · Ulixertinib in People With Histiocytic Neoplasms brief
F. Stephen Hodi
Dana-Farber Cancer Institute · 1 of 1 trials Phase 2+
Ph2NCT03417739 · A Phase II Study of BVD-523 in Metastatic Uveal Melanoma brief
Keith T Flaherty
ECOG-ACRIN Cancer Research Group · 1 of 1 trials Phase 2+
Ph2NCT02465060 · Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)brief
Kieuhoa T Vo
Children's Oncology Group · 1 of 1 trials Phase 2+
Ph2NCT03698994 · Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)brief
Raajit Rampal
Memorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
Ph1/Ph2NCT06773195 · A Study of Ruxolitinib in Combination With Ulixertinib in People With Myelofibrosis brief
Vivek Subbiah
ECOG-ACRIN Cancer Research Group · 1 of 1 trials Phase 2+
Ph2NCT06400225 · Testing BVD-523FB (Ulixertinib) as Potentially Targeted Treatment in Cancers With Genetic Changes (MATCH - Subprotocol Z1L)brief
Christine Parseghian
M.D. Anderson Cancer Center · 0 of 1 trials Phase 2+
Ph1NCT05985954 · Open-label Phase 1b Study of Ulixertinib and Cetuximab or Ulixertinib in Combination With Cetuximab and Encorafenib in Patients With Unresectable or Metastatic Colorectal Cancer Who Have Previously Received EGFR or BRAF-directed Therapy brief
Nazanin Majd
M.D. Anderson Cancer Center · 0 of 1 trials Phase 2+
Early Ph1NCT05804227 · Window-of-Opportunity Trial of Ulixertinib for MAPK-Activated Gliomas brief
Stergios Moschos
University of North Carolina, Chapel Hill · 0 of 1 trials Phase 2+
Ph1NCT03454035 · Ulixertinib/Palbociclib in Patients With Advanced Pancreatic and Other Solid Tumors brief

10 of 13 trials of drugs against MAPK1 have sites only in United States

Registry trials of ulixertinib, temuterkib 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; 10 of 13 have all sites in one country.

Sites only in this groupSites here and elsewhere

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. Source: ClinicalTrials.gov, fetched live.

7 trials of drugs against MAPK1 were stopped early; 1 give no reason

Terminated, withdrawn and suspended interventional trials of ulixertinib, temuterkib, ravoxertinib, ASN007, MK-8353, KO-947, 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 7 most recent of 7.

Ph2NCT03417739 brief why it stopped
terminated · 2026-07-27 · Dana-Farber Cancer Institute · matched by the registry's drug synonyms
“This was a Simon two stage design trial that terminated after the first stage due to lack of response.”
Ph2NCT05221320 brief why it stopped
terminated · 2025-09-25 · BioMed Valley Discoveries, Inc · Ulixertinib
“Lack of Enrollment for Remaining Open Baskets”
Ph1NCT02972034 brief why it stopped
terminated · 2024-11-21 · Merck Sharp & Dohme LLC · MK-8353
“business reasons.”
Ph2NCT04488003 brief why it stopped
terminated · 2024-06-04 · BioMed Valley Discoveries, Inc · Ulixertinib
“Enrollment challenges”
Ph1NCT03051035 brief why it stopped
terminated · 2021-09-20 · Kura Oncology, Inc. · KO-947
“Due to a strategic business decision Kura has stopped development of KO-947. Neither safety nor efficacy reasons were the cause of study termination.”
Ph1NCT02608229 brief why it stopped
terminated · 2021-04-21 · Washington University School of Medicine · matched by the registry's drug synonyms
“Adverse events”
Ph1NCT01358331 brief why it stopped
terminated · 2020-04-02 · Merck Sharp & Dohme LLC · MK-8353
No reason given

Paediatric incentives and obligations for MAPK1's drugs

For ulixertinib, temuterkib, ravoxertinib, ASN007, MK-8353, KO-947: 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 · MAPK1 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: no · No EMA paediatric investigation plan decision names ulixertinib, temuterkib, ravoxertinib, asn007, mk-8353, ko-947
Rule: 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: no · No EU orphan designation names ulixertinib, temuterkib, ravoxertinib, asn007, mk-8353, ko-947
Rule: 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 ulixertinib, temuterkib, ravoxertinib, asn007, mk-8353, ko-947
Rule: 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 link
Rule: 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 ulixertinib, temuterkib, ravoxertinib, asn007, mk-8353, ko-947
Rule: 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 · 3 interventional studies of ulixertinib, temuterkib, ravoxertinib, asn007, mk-8353, ko-947 include patients under 18; 3 are recruiting, not yet recruiting or active
Rule: 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.

Drug	Type	Highest stage	Indications	Source records
ULIXERTINIB	Small molecule	phase 2	melanoma, lymphoma, plasma cell myeloma, non-Hodgkin lymphoma, uveal melanoma, gastroesophageal junction adenocarcinoma, cholangiocarcinoma, esophageal adenocarcinoma, +14 more	Open Targets · ChEMBL
TEMUTERKIB	Small molecule	phase 2	exocrine pancreatic carcinoma, neoplasm, colorectal cancer, cancer, Waldenstrom macroglobulinemia, neoplasm of mature B-cells, B-cell chronic lymphocytic leukemia, mantle cell lymphoma, +4 more	Open Targets · ChEMBL
RAVOXERTINIB	Small molecule	phase 1	–	Open Targets · ChEMBL
ASN007	Small molecule	phase 1	colorectal cancer, pancreatic ductal adenocarcinoma, non-small cell lung carcinoma, melanoma	Open Targets · ChEMBL
MK-8353	Small molecule	phase 1	colorectal cancer, melanoma	Open Targets · ChEMBL
KO-947	Small molecule	phase 1	–	Open Targets · ChEMBL