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Therapy Name | PD-0325901 |
Synonyms | |
Therapy Description |
PD-0325901, a derivative of CI-1040, is a pan-MEK inhibitor, which inhibits activation of MAPK/ERK resulting in decreased tumor cell proliferation (PMID: 18952427, PMID: 32147669). |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
PD-0325901 | PD0325901|PD 0325901|PD-901|Mirdametinib | MEK inhibitor (Pan) 26 MEK1 Inhibitor 26 MEK2 Inhibitor 24 | PD-0325901, a derivative of CI-1040, is a pan-MEK inhibitor, which inhibits activation of MAPK/ERK resulting in decreased tumor cell proliferation (PMID: 18952427, PMID: 32147669). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF V600E | melanoma | conflicting | PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PD-0325901 treatment induced cell cycle arrest and inhibited growth of melanoma cells harboring BRAF V600E in culture (PMID: 25422890). | 25422890 |
BRAF V600E | melanoma | conflicting | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, PD-0325901 inhibited growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 26267534). | 26267534 |
BRAF V600E | melanoma | conflicting | PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a melanoma cell line xenograft model harboring BRAF V600E treated with PD-0325901 demonstrated stable tumor growth, but by day 44, growth ensued and thus, demonstrated no benefit (PMID: 27488531). | 27488531 |
BRAF V600E MAP2K1 I103N | melanoma | resistant | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, overexpression of MAP2K1 I103N in melanoma cells harboring BRAF V600E resulted in insensitivity to growth inhibition by PD-0325901 in cell culture (PMID: 26267534). | 26267534 |
BRAF V600E | glioblastoma | conflicting | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated a decreased response to treatment with PD-0325901, demonstrating increased viability of CD133 positive cells in culture (PMID: 26573800). | 26573800 |
BRAF V600E | glioblastoma | conflicting | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, PD-0325901 inhibited growth of glioblastoma cell lines harboring BRAF V600E in culture (PMID: 38714355). | 38714355 |
BRAF V600E | colon cancer | sensitive | PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PD-0325901 demonstrated antitumor activity against BRAF V600E colon cancer cell line xenografts (PMID: 16273091). | 16273091 |
MAP2K1 Q56P | lung adenocarcinoma | sensitive | PD-0325901 | Preclinical | Actionable | In a preclinical study, a lung adenocarcinoma cell line harboring MAP2K1 Q56P demonstrated sensitivity to PD-0325901, resulting in decreased cell viability (PMID: 26582713). | 26582713 |
NRAS Q61L | acute myeloid leukemia | predicted - sensitive | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, PD-0325901 treatment induced apoptosis and inhibited proliferation of an acute myeloid leukemia cell line harboring NRAS Q61L in culture (PMID: 28923853). | 28923853 |
KIT W557_K558del | gastrointestinal stromal tumor | sensitive | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, PD-0325901 treatment inhibited Erk phosphorylation and decreased expression of ETV1 and CXCR4 in gastrointestinal stromal tumor cells harboring KIT W557_K558del (PMID: 26936919). | 26936919 |
BRAF N486_P490del | ovarian cancer | sensitive | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated sensitivity to PD-0325901, resulting in decreased cell viability in culture (PMID: 26996308). | 26996308 |
NRAS Q61R | melanoma | sensitive | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, PD-0325901 treatment induced cell cycle arrest and inhibited growth of melanoma cells harboring NRAS Q61R in culture (PMID: 25422890). | 25422890 |
BRAF N486_P490del | melanoma | sensitive | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated sensitivity to PD-0325901, resulting in decreased cell viability in culture (PMID: 26996308). | 26996308 |
BRAF V600E MAP2K1 L115P | melanoma | resistant | PD-0325901 | Preclinical | Actionable | In a preclinical study, overexpression of MAP2K1 L115P in melanoma cells harboring BRAF V600E resulted in insensitivity to growth inhibition by PD-0325901 in cell culture (PMID: 26267534). | 26267534 |
NRAS mutant | melanoma | no benefit | PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PD-0325901 treatment resulted in stable tumor growth in melanoma cell line xenograft models harboring an NRAS mutation, however, growth later ensued and thus, demonstrates a lack of benefit (PMID: 27488531). | 27488531 |
NRAS G75_E76insDSAMRDQYMRTG | myelodysplastic/myeloproliferative neoplasm | sensitive | PD-0325901 | Preclinical | Actionable | In a preclinical study, PD-0325901 decreased the accumulation of immature myeloid cells in a zebrafish model of myelodysplastic/myeloproliferative neoplasm harboring NRAS G75_E76insDSAMRDQYMRTG (PMID: 38522505). | 38522505 |
BRAF V600E | colorectal cancer | sensitive | PD-0325901 | Preclinical | Actionable | In a preclinical study, PD-0325901 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 26267534). | 26267534 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT01347866 | Phase I | Gedatolisib PD-0325901 Irinotecan | Clinical Study Of PI3K/mTOR Inhibitors In Combination With An Oral MEK Inhibitor Or Irinotecan In Patients With Advanced Cancer | Terminated | USA | ITA | ESP | CAN | 0 |
NCT03962543 | Phase II | PD-0325901 | MEK Inhibitor Mirdametinib (PD-0325901) in Patients With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas (ReNeu) | Active, not recruiting | USA | 0 |
NCT04923126 | Phase Ib/II | PD-0325901 | SJ901: Evaluation of Mirdametinib in Children, Adolescents, and Young Adults With Low-Grade Glioma | Recruiting | USA | 0 |
NCT02096471 | Phase II | PD-0325901 | MEK Inhibitor PD-0325901 Trial in Adolescents and Adults With NF1 | Completed | USA | 0 |