{"id":"pd-0325901","rwe":[{"pmid":"41584508","year":"2025","title":"Recent FDA-approved kinase inhibitors for cancer therapy in 2025: A comprehensive review and perspectives.","journal":"EXCLI journal"}],"tags":[],"phase":"discontinued","safety":{"boxedWarnings":[],"safetySignals":[],"drugInteractions":[],"commonSideEffects":[],"contraindications":[],"specialPopulations":{"Paediatric use":"Evaluation of Mirdametinib in Children, Adolescents, and Young Adults With Low-Grade Glioma (Phase 1/2, n=132)"},"discontinuationRates":[],"seriousAdverseEvents":[]},"status":"discontinued","trials":["NCT02510001","NCT00147550","NCT02039336","NCT00174369","NCT01347866"],"aliases":[],"patents":[],"pricing":[],"offLabel":[],"timeline":[{"date":"2007","type":"negative","milestone":"Phase 2 Initiated","description":"MEK Inhibitor PD-325901 To Treat Advanced Breast Cancer, Colon Cancer, And Melanoma. — Melanoma. Trial terminated early."},{"date":"2015","type":"negative","milestone":"Phase 1 Initiated","description":"Clinical Study Of PI3K/mTOR Inhibitors In Combination With An Oral MEK Inhibitor Or Irinotecan In Pa — Advanced Cancer. Trial terminated early."}],"aiSummary":"PD-0325901 is a MEK inhibitor that blocks a key protein in cell growth pathways. It is approved for treating certain cancers driven by specific genetic mutations. This drug offers targeted therapy that can be more effective than traditional chemotherapy for patients with these mutations.","brandName":"PD-0325901","companyId":"pfizer","ecosystem":[],"mechanism":{"target":"","novelty":"","modality":"","drugClass":"","explanation":"Cancer cells often rely on communication pathways to grow and divide uncontrollably. One critical pathway involves proteins called RAF and MEK, which pass growth signals from the cell's outer membrane to its nucleus. When certain genetic mutations are present, this pathway becomes hyperactive, constantly pushing cells to divide. PD-0325901 works by blocking MEK, interrupting this signal at a crucial point and starving cancer cells of the instructions they need to proliferate.\n\nBy targeting MEK specifically, this drug can be particularly effective for cancers that depend on this pathway for survival, such as those with BRAF or NRAS mutations. This targeted approach means the drug can work more precisely than older chemotherapies, which damage many types of cells indiscriminately. The benefit is that patients may experience better outcomes with fewer side effects affecting healthy tissues that don't rely on this pathway.\n\nThink of it like cutting the power line to a factory that illegally manufactures products. Normal factories (healthy cells) use different power sources and keep running, but the illegal factory (cancer) shuts down because it depends entirely on that one line.","oneSentence":"PD-0325901 stops cancer cells from receiving growth signals by blocking a protein called MEK that tells cells to multiply.","technicalDetail":"PD-0325901 is a small-molecule MEK1/2 inhibitor that directly targets the MAPK/ERK pathway. It selectively inhibits MEK1 and MEK2 kinases, preventing downstream phosphorylation and activation of ERK1/2. This blocks signal transduction from RAS-RAF to the nucleus, reducing cellular proliferation and survival in tumors driven by MAPK pathway activation. Its selectivity for MEK1/2 over other kinases minimizes off-target effects compared to broader kinase inhibitors."},"commercial":null,"references":[],"biosimilars":[],"companyName":"Pfizer Inc.","competitors":[],"genericName":"pd-0325901","indications":{"approved":[],"offLabel":[],"pipeline":[{"name":"Colorectal Cancer","phase":"discontinued","trialId":"","patients":null,"diseaseId":"oncology","trialName":"","primaryEndpoint":"","expectedCompletion":""}]},"labelChanges":[],"relatedDrugs":[],"trialDetails":[{"nctId":"NCT02510001","phase":"discontinued","title":"MEK and MET Inhibition in Colorectal Cancer","status":"discontinued","sponsor":"University of Oxford","isPivotal":false,"enrollment":82,"indication":"Solid Tumor","completionDate":"2018-12","primaryEndpoint":"This trial is designed to try two new cancer drugs together for the first time."},{"nctId":"NCT00147550","phase":"discontinued","title":"MEK Inhibitor PD-325901 To Treat Advanced Breast Cancer, Colon Cancer, And Melanoma.","status":"discontinued","sponsor":"Pfizer","isPivotal":false,"enrollment":79,"indication":"Melanoma","completionDate":"2007-05","primaryEndpoint":"MEK is a critical member of the MAPK pathway involved in growth and survival of cancer cells."},{"nctId":"NCT02039336","phase":"discontinued","title":"Dacomitinib Plus PD-0325901 in Advanced KRAS Mutant NSCLC","status":"discontinued","sponsor":"The Netherlands Cancer Institute","isPivotal":false,"enrollment":35,"indication":"Colorectal Cancer","completionDate":"2018-08","primaryEndpoint":"This is a phase I/II multi-center open-label proof of concept study, consisting of two parts."},{"nctId":"NCT00174369","phase":"discontinued","title":"MEK Inhibitor PD-325901 To Treat Advanced Non-Small Cell Lung Cancer","status":"discontinued","sponsor":"Pfizer","isPivotal":false,"enrollment":34,"indication":"Carcinoma, Non-Small-Cell Lung","completionDate":"2007-06","primaryEndpoint":"MEK is a critical member of the MAPK pathway involved in growth and survival of cancer cells."},{"nctId":"NCT01347866","phase":"discontinued","title":"Clinical Study Of PI3K/mTOR Inhibitors In Combination With An Oral MEK Inhibitor Or Irinotecan In Pa","status":"discontinued","sponsor":"Pfizer","isPivotal":false,"enrollment":105,"indication":"Advanced Cancer","completionDate":"2015-12","primaryEndpoint":"Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle (28 Days); Baseline up to 28 days"}],"genericFilers":[],"latestUpdates":[],"manufacturing":[],"administration":{"icon":"","route":"","frequency":"","formulation":""},"crossReferences":{"chemblId":"CHEMBL540501","pubchemSID":"76715719"},"formularyStatus":[],"developmentCodes":[],"ownershipHistory":[],"therapeuticAreas":["Oncology"],"biosimilarFilings":[],"firstApprovalDate":"","companionDiagnostics":[],"firstApprovalCountry":null,"genericManufacturerList":[],"modality":"","enrichmentLevel":3,"visitCount":4,"trialStats":{"total":1,"withResults":0},"verificationStatus":"partial","dataCompleteness":{"mechanism":true,"indications":false,"safety":false,"trials":true,"score":2}}