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Therapy Name | MRK-003 |
Synonyms | |
Therapy Description |
MRK-003 is a gamma-secretase inhibitor which inhibits Notch3 signaling and induces apoptosis in cancer cells (PMID: 17804716). |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
MRK-003 | Gamma secretase inhibitor 12 | MRK-003 is a gamma-secretase inhibitor which inhibits Notch3 signaling and induces apoptosis in cancer cells (PMID: 17804716, PMID: 23887890). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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NOTCH1 V1676I | osteosarcoma | sensitive | MRK-003 | Preclinical | Actionable | In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 V1676I in culture (PMID: 25104330). | 25104330 |
NOTCH1 R1683W | osteosarcoma | sensitive | MRK-003 | Preclinical | Actionable | In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 R1683W in culture (PMID: 25104330). | 25104330 |
NOTCH1 rearrange | triple-receptor negative breast cancer | sensitive | MRK-003 | Preclinical | Actionable | In a preclinical study, MRK-003 inhibited growth of triple receptor-negative breast cancer cells harboring NOTCH1 rearrangement in culture and reduced tumor growth in xenograft models (PMID: 25104330). | 25104330 |
Unknown unknown | brain stem glioma | not applicable | MRK-003 | Preclinical - Cell culture | Actionable | In a preclinical study, MRK-003 increased apoptosis and decreased growth of diffuse pontine glioma cell lines in culture (PMID: 26115193). | 26115193 |
NOTCH1 A1707T | Advanced Solid Tumor | sensitive | MRK-003 | Preclinical | Actionable | In a preclinical study, transformed cells expressing NOTCH1 A1707T demonstrated sensitivity to MRK-003 in culture (PMID: 25104330). | 25104330 |
Unknown unknown | juvenile astrocytoma | not applicable | MRK-003 | Preclinical | Actionable | In a preclinical study, MRK-003 inhibited HES1 expression in pediatric low-grade astrocytoma cell lines in culture and decreased migration in 1 of 2 cell lines, but did not have a significant effect on cell growth (PMID: 25575134). | 25575134 |
NOTCH1 V1575A | osteosarcoma | sensitive | MRK-003 | Preclinical | Actionable | In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 V1575A in culture (PMID: 25104330). | 25104330 |
FBXW7 R479Q | T-cell adult acute lymphocytic leukemia | resistant | MRK-003 | Preclinical | Actionable | In a preclinical study, FBXW7 R479Q conferred resistance to gamma secretase inhibitor, MRK-003, by activation of the NOTCH pathway and stablization of MYC as demonstrated in T cell acute lymphoblastic leukemia (T-ALL) cell lines (PMID: 17646409). | 17646409 |
NOTCH1 A1707T | osteosarcoma | sensitive | MRK-003 | Preclinical | Actionable | In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 A1707T in culture (PMID: 25104330). | 25104330 |
FBXW7 R465C | T-cell adult acute lymphocytic leukemia | resistant | MRK-003 | Preclinical | Actionable | In a preclinical study, FBXW7 R465C conferred resistance to gamma secretase inhibitor, MRK-003, by activation of the NOTCH pathway and stablization of MYC as demonstrated in T cell acute lymphoblastic leukemia (T-ALL) cell lines (PMID: 17646409). | 17646409 |
NOTCH1 wild-type | triple-receptor negative breast cancer | decreased response | MRK-003 | Preclinical | Actionable | In a preclinical study, triple receptor-negative breast cancer xenograft models harboring wild-type NOTCH1 demonstrated reduced sensitivity to MRK-003 induced tumor growth inhibition (PMID: 25104330). | 25104330 |
NOTCH1 A1570G | osteosarcoma | sensitive | MRK-003 | Preclinical | Actionable | In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 A1570G in culture (PMID: 25104330). | 25104330 |
FBXW7 R505L | T-cell adult acute lymphocytic leukemia | resistant | MRK-003 | Preclinical | Actionable | In a preclinical study, FBXW7 R505L may conferred resistance to gamma secretase inhibitor, MRK-003, by activation of the NOTCH pathway and stablization of MYC as demonstrated in T cell acute lymphoblastic leukemia (T-ALL) cell lines (PMID: 17646409). | 17646409 |
NOTCH1 I1680S | osteosarcoma | sensitive | MRK-003 | Preclinical | Actionable | In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 I1680S in culture (PMID: 25104330). | 25104330 |
NOTCH1 E1567K | osteosarcoma | sensitive | MRK-003 | Preclinical | Actionable | In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 E1567K in culture (PMID: 25104330). | 25104330 |
NOTCH1 A1552V | osteosarcoma | sensitive | MRK-003 | Preclinical | Actionable | In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 A1552V in culture (PMID: 25104330). | 25104330 |
FBXW7 R505C | T-cell adult acute lymphocytic leukemia | resistant | MRK-003 | Preclinical | Actionable | In a preclinical study, FBXW7 R505C conferred resistance to gamma secretase inhibitor, MRK-300, by activation of the NOTCH pathway and stablization of MYC as demonstrated in T cell acute lymphoblastic leukemia (T-ALL) cell lines (PMID: 17646409). | 17646409 |
NOTCH1 V1599M | osteosarcoma | sensitive | MRK-003 | Preclinical | Actionable | In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 V1599M in culture (PMID: 25104330). | 25104330 |
NOTCH1 A1552G | osteosarcoma | sensitive | MRK-003 | Preclinical | Actionable | In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 A1552G in culture (PMID: 25104330). | 25104330 |
FBXW7 R465H | T-cell adult acute lymphocytic leukemia | resistant | MRK-003 | Preclinical | Actionable | In a preclinical study, FBXW7 R465H conferred resistance to gamma secretase inhibitor, MRK-003, by activation of the NOTCH pathway and stablization of MYC as demonstrated in T cell acute lymphoblastic leukemia (T-ALL) cell lines (PMID: 17646409). | 17646409 |
FBXW7 del | T-cell adult acute lymphocytic leukemia | resistant | MRK-003 | Preclinical | Actionable | In a preclinical study, homozygous deletion of FBXW7 is conferred resistance to gamma secretase inhibitor, MRK-003, by activation of the NOTCH pathway and stablization of MYC as demonstrated in T cell acute lymphoblastic leukemia (T-ALL) cell lines (PMID: 17646409). | 17646409 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
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