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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, PMID: 23887890).

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Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
MRK-003			Gamma secretase inhibitor 13	MRK-003 is a gamma-secretase inhibitor which inhibits Notch3 signaling and induces apoptosis in cancer cells (PMID: 17804716, PMID: 23887890).

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

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