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Therapy Name | E6201 |
Synonyms | |
Therapy Description |
E6201 is a dual inhibitor of MEK1 and FLT3, which may lead to decreased tumor cell growth (Blood Nov 2013, 122 (21) 2683; PMID: 23039341, PMID: 29867224, PMID: 30264293). |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
E6201 | FLT3 Inhibitor 69 MEK1 Inhibitor 26 | E6201 is a dual inhibitor of MEK1 and FLT3, which may lead to decreased tumor cell growth (Blood Nov 2013, 122 (21) 2683; PMID: 23039341, PMID: 29867224, PMID: 30264293). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
HRAS wild-type | melanoma | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and hypersensitivity was associated with wild-type HRAS (PMID: 23039341). | 23039341 |
BRAF mut PTEN mut | melanoma | decreased response | E6201 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, E6201 resulted in a cytostatic response in melanoma cell lines harboring both BRAF and PTEN mutations in culture and only inhibited tumor growth at very high doses in cell line xenograft models (PMID: 23039341). | 23039341 |
FLT3 exon 14 ins FLT3 F691L | leukemia | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines harboring FLT3 F691L in addition to FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). | 26822154 |
BRAF V600E | melanoma | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited Mapk pathway activation and proliferation of melanoma cell lines harboring BRAF V600E mutation in culture (PMID: 24448821). | 24448821 |
BRAF V600E | melanoma | sensitive | E6201 | Case Reports/Case Series | Actionable | In a Phase I trial, a patient with metastatic melanoma and brain metastasis harboring BRAF V600E demonstrated an ongoing near complete response with an overall survival of more than 8 years, and preclinical analysis of melanoma cell lines harboring homozygous or heterozygous BRAF V600E in culture were sensitive to treatment with E6201 (PMID: 30264293). | 30264293 |
BRAF mut PTEN wild-type | melanoma | sensitive | E6201 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, E6201 resulted in a cytocidal response in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture and inhibited tumor growth in cell line xenograft models (PMID: 23039341). | 23039341 |
BRAF mutant | melanoma | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and hypersensitivity was associated with BRAF mutations (PMID: 23039341). | 23039341 |
NRAS wild-type | melanoma | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and hypersensitivity was associated with wild-type NRAS (PMID: 23039341). | 23039341 |
FLT3 D835Y | leukemia | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines over expressing FLT3 D835Y in culture (PMID: 26822154). | 26822154 |
FLT3 D835G | acute myeloid leukemia | sensitive | E6201 | Preclinical - Cell culture | Actionable | In a preclinical study, E6201 induced apoptosis in blast samples derived from acute myeloid leukemia patients harboring FLT3 D835G in culture (PMID: 26822154). | 26822154 |
FLT3 D835G | leukemia | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines over expressing FLT3 D835G in culture (PMID: 26822154). | 26822154 |
FLT3 D835Y | acute myeloid leukemia | sensitive | E6201 | Preclinical - Cell culture | Actionable | In a preclinical study, E6201 induced apoptosis in blast samples derived from acute myeloid leukemia patients harboring FLT3 D835Y in culture (PMID: 26822154). | 26822154 |
FLT3 Y599_D600insSTDNEYFYVDFREYEY | acute myeloid leukemia | predicted - sensitive | E6201 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, E6201 induced cell death, inhibited cell growth, and decreased tumor burden in acute myeloid leukemia cells harboring FLT3-ITD mutations in culture and in cell line xenograft models (Blood Nov 2013, 122 (21) 2683). | detail... |
FLT3 mutant | acute myeloid leukemia | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, acute myeloid leukemia cell lines harboring FLT3 mutations demonstrated increased sensitivity to E6201 induced growth inhibition and apoptosis in culture compared to FLT3 wild-type cells (PMID: 26822154). | 26822154 |
BRAF V600E MAP2K1 C121S | melanoma | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited Mapk pathway activation and proliferation of melanoma cell line harboring BRAF V600E mutation and overexpressing MAP2K1 C121S in culture (PMID: 24448821). | 24448821 |
FLT3 exon 14 ins FLT3 N676D FLT3 Y842C | leukemia | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines harboring FLT3 N676D and Y842C in addition to FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). | 26822154 |
FLT3 exon 14 ins | leukemia | sensitive | E6201 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, E6201 induced growth inhibition and apoptosis in leukemia cell lines harboring FLT3 internal tandem duplications (ITD) and reduced tumor burden in xenograft models (PMID: 26822154). | 26822154 |
FLT3 exon 14 ins FLT3 Y842C | leukemia | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines harboring FLT3 Y842C in addition to FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). | 26822154 |
FLT3 exon 14 ins | acute myeloid leukemia | sensitive | E6201 | Preclinical - Cell culture | Actionable | In a preclinical study, E6201 induced apoptosis in blast samples derived from acute myeloid leukemia patients harboring FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). | 26822154 |
PTEN wild-type | melanoma | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and sensitivity was associated with wild-type PTEN (PMID: 23039341). | 23039341 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT02418000 | Phase Ib/II | E6201 | A Study of E6201 for the Treatment of Advanced Hematologic Malignancies With FLT3 Mutation | Terminated | USA | 0 |
NCT03332589 | Phase I | Dabrafenib + E6201 E6201 | E6201 Plus Dabrafenib for the Treatment of Metastatic Melanoma Central Nervous System Metastases (CNS) | Terminated | USA | 0 |