Therapy Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

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).

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

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).

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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
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
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
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
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 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 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 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
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 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 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 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
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
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 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
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 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
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
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

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Clinical Trial Phase Therapies Title Recruitment Status


Additional content available in CKB BOOST