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Therapy Name | CI-1040 |
Synonyms | |
Therapy Description |
CI-1040 (PD184352) binds and inhibits Mek1 and Mek2, which may inhibit the activation of downstream signaling targets and reduce tumor cell proliferation (PMID: 14613031, PMID: 16009947). |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
CI-1040 | PD184352|PD-184352 | MEK inhibitor (Pan) 26 MEK1 Inhibitor 26 MEK2 Inhibitor 24 | CI-1040 (PD184352) binds and inhibits Mek1 and Mek2, which may inhibit the activation of downstream signaling targets and reduce tumor cell proliferation (PMID: 14613031, PMID: 16009947). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
MAP2K1 I111A | Advanced Solid Tumor | decreased response | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, MAP2K1 I111A demonstrated decreased sensitivity to CI-1040 (PD184352) in an in vitro kinase assay (PMID: 12370306). | 12370306 |
BRAF T529I BRAF V600E | Advanced Solid Tumor | sensitive | CI-1040 | Preclinical | Actionable | In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation in transformed cells expressing BRAF V600E and the gatekeeper mutation BRAF T529I in culture (PMID: 20538618). | 20538618 |
BRAF V600E | ovarian cancer | sensitive | CI-1040 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, CI-1040 inhibited growth of a human ovarian cancer cell line harboring BRAF V600E in culture, and inhibited tumor growth in xenograft models (PMID: 19018267). | 19018267 |
MAP2K1 L118Q | Advanced Solid Tumor | predicted - resistant | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of MAP2K1 L118Q in an in vitro assay (PMID: 12370306). | 12370306 |
MAP2K1 L118D | Advanced Solid Tumor | predicted - resistant | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of MAP2K1 L118D in an in vitro assay (PMID: 12370306). | 12370306 |
BRAF V600E MAP2K1 I111N | melanoma | resistant | CI-1040 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 I111N in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 |
MAP2K1 I139R | Advanced Solid Tumor | decreased response | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, MAP2K1 I139R demonstrated decreased sensitivity to CI-1040 (PD184352) in an in vitro kinase assay (PMID: 12370306). | 12370306 |
MAP2K1 L115P | Advanced Solid Tumor | resistant | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of MAP2K1 L115P in an in vitro assay and failed to suppress Erk phosphorylation in cells expressing MAP2K1 L115P in culture (PMID: 12370306). | 12370306 |
MAP2K1 F53S | Advanced Solid Tumor | sensitive | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) inhibited kinase activity of MAP2K1 F53S in an in vitro assay and decreased Erk phosphorylation in cells expressing MAP2K1 F53S in culture (PMID: 12370306). | 12370306 |
MAP2K1 L118G | Advanced Solid Tumor | decreased response | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, MAP2K1 L118G demonstrated decreased sensitivity to CI-1040 (PD184352) in an in vitro kinase assay (PMID: 12370306). | 12370306 |
BRAF V600E MAP2K1 H119P | melanoma | resistant | CI-1040 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 H119P in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 |
MAP2K1 I111R | Advanced Solid Tumor | predicted - resistant | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of MAP2K1 I111R in an in vitro assay (PMID: 12370306). | 12370306 |
MAP2K1 I139N | Advanced Solid Tumor | decreased response | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, MAP2K1 I139N demonstrated decreased sensitivity to CI-1040 (PD184352) in an in vitro kinase assay (PMID: 12370306). | 12370306 |
MAP2K1 L118P | Advanced Solid Tumor | predicted - resistant | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of MAP2K1 L118P in an in vitro assay (PMID: 12370306). | 12370306 |
MAP2K1 L115A | Advanced Solid Tumor | decreased response | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, MAP2K1 L115A demonstrated decreased sensitivity to CI-1040 (PD184352) in an in vitro kinase assay (PMID: 12370306). | 12370306 |
HRAS G12V | melanoma | sensitive | CI-1040 | Preclinical | Actionable | In a preclinical study CI-1040 (PD-184352) inhibited melanoma progression in a transgenic zebrafish model of melanoma expressing HRAS G12V (PMID: 26267534). | 26267534 |
BRAF V600E MAP2K1 V211D | melanoma | resistant | CI-1040 | Preclinical | Actionable | In a preclinical study, expression of MAP2K1 V211D in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 |
BRAF V600E MAP2K1 I103N | melanoma | resistant | CI-1040 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 I103N in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 |
BRAF T529N BRAF V600E | Advanced Solid Tumor | sensitive | CI-1040 | Preclinical | Actionable | In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation and growth of transformed cells expressing BRAF V600E and the gatekeeper mutation BRAF T529N in culture (PMID: 20538618). | 20538618 |
BRAF V600E MAP2K1 L115R | melanoma | resistant | CI-1040 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 L115R in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 |
MAP2K1 I111D | Advanced Solid Tumor | predicted - resistant | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of MAP2K1 I111D in an in vitro assay (PMID: 12370306). | 12370306 |
MAP2K1 I139G | Advanced Solid Tumor | predicted - resistant | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of MAP2K1 I139G in an in vitro assay (PMID: 12370306). | 12370306 |
BRAF V600E MAP2K1 L115P | melanoma | resistant | CI-1040 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 L115P in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 |
BRAF V600E | Advanced Solid Tumor | sensitive | CI-1040 | Preclinical | Actionable | In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation and growth of transformed cells expressing BRAF V600E in culture (PMID: 20538618). | 20538618 |
BRAF V600E MAP2K1 I99T | melanoma | resistant | CI-1040 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 I99T in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 |
MAP2K1 I111P | Advanced Solid Tumor | predicted - resistant | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of MAP2K1 I111P in an in vitro assay (PMID: 12370306). | 12370306 |
BRAF T529M BRAF V600E | Advanced Solid Tumor | predicted - sensitive | CI-1040 | Preclinical | Actionable | In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation in transformed cells expressing BRAF V600E and the gatekeeper mutation BRAF T529M in culture (PMID: 20538618). | 20538618 |
MAP2K1 I103N | Advanced Solid Tumor | decreased response | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, MAP2K1 I103N demonstrated decreased sensitivity to CI-1040 (PD184352) in an in vitro kinase assay (PMID: 12370306). | 12370306 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
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