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 GSK126
Synonyms
Therapy Description

GSK126 selectively inhibits EZH2, resulting in decreased H3K27 tri-methylation, and potentially leading to decreased tumor cell proliferation and reduced tumor growth (PMID: 23051747, PMID: 25686104).

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
GSK126 GSK2816126|GSK-126 EZH2 inhibitor 18 GSK126 selectively inhibits EZH2, resulting in decreased H3K27 tri-methylation, and potentially leading to decreased tumor cell proliferation and reduced tumor growth (PMID: 23051747, PMID: 25686104, PMID: 31471312).

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
EZH2 Y641H melanoma predicted - sensitive GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 inhibited H3K27 trimethylation and reversed transcriptional silencing in human melanoma cells harboring EZH2 Y641H in culture (PMID: 26936398). 26936398
ARID1A mutant ovarian cancer sensitive GSK126 Preclinical - Cell line xenograft Actionable In a preclinical study, GSK126 selectively inhibited growth of ARID1A-mutant ovarian cancer cells in culture, and induced tumor regression in ARID1A-mutant ovarian cancer xenograft models (PMID: 25686104). 25686104
EZH2 Y111D EZH2 A677G B-cell lymphoma resistant GSK126 Preclinical - Cell culture Actionable In a preclinical study, EZH2 Y111D conferred resistance to GSK126 when occurred in the same allele as EZH2 A677G in B-cell lymphoma cells in culture (PMID: 26360609). 26360609
ATRX fusion neuroblastoma predicted - sensitive GSK126 Preclinical - Cell culture Actionable In a preclinical study, treatment with GSK126 resulted in reduced proliferation and increased apoptosis of neuroblastoma cell lines harboring in-frame ATRX fusions in culture (PMID: 31631027). 31631027
EZH2 Y111D EZH2 Y641F Advanced Solid Tumor predicted - resistant GSK126 Preclinical - Cell culture Actionable In a preclinical study, transformed cells overexpressing EZH2 and carrying simultaneous Y641F and Y111D mutations demonstrated reduced sensitivity to GSK126 in culture (PMID: 26360609). 26360609
EZH2 Y111D Advanced Solid Tumor resistant GSK126 Preclinical - Cell culture Actionable In a preclinical study, over expression of EZH2 Y111D in transformed cells harboring wild-type Ezh2 resulted in resistance to GSK126 treatment in culture (PMID: 26360609). 26360609
ARID1A wild-type ovarian cancer no benefit GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 had no significant effect on the growth of ovarian cancer cells with wild-type ARID1A in culture (PMID: 25686104). 25686104
Unknown unknown Advanced Solid Tumor not applicable GSK126 Phase I Actionable In a Phase I trial, GSK126 was tolerated and demonstrated preliminary efficacy, resulted in partial response in 2% (1/41) and stable disease in 34% (14/41) of patients with advanced solid tumor (n=21) or B-cell lymphoma (n=20) (PMID: 31471312; NCT02082977). 31471312
EZH2 Y641S melanoma predicted - sensitive GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 reversed transcriptional silencing in human melanoma cells harboring wild-type EZH2 Y641S in culture (PMID: 26936398). 26936398
EZH2 Y641N melanoma predicted - sensitive GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 inhibited H3K27 trimethylation and reversed transcriptional silencing in human melanoma cells harboring EZH2 Y641N in culture (PMID: 26936398). 26936398
EZH2 Y641N diffuse large B-cell lymphoma no benefit GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 alone did not alter cell-cycle progression in survival in a diffuse large B-cell lymphoma cell line harboring EZH2 Y641N in culture (PMID: 25605023). 25605023
EZH2 Y641N diffuse large B-cell lymphoma no benefit GSK126 Preclinical - Cell culture Actionable In a preclinical study, treatment with GSK126 alone did not result in reduced cell viability in a diffuse large B-cell lymphoma cell line harboring EZH2 Y641N in culture (PMID: 32906688). 32906688
Unknown unknown B-cell lymphoma not applicable GSK126 Phase I Actionable In a Phase I trial, GSK126 was tolerated and demonstrated preliminary efficacy, resulted in partial response in 2% (1/41) and stable disease in 34% (14/41) of patients with advanced solid tumor (n=21) or B-cell lymphoma (n=20) (PMID: 31471312; NCT02082977). 31471312
EZH2 Y641S diffuse large B-cell lymphoma decreased response GSK126 Preclinical - Cell culture Actionable In a preclinical study, treatment with GSK126 did not alter cell-cycle progression or decrease survival in a diffuse large B-cell lymphoma cell line harboring EZH2 Y641S in culture (PMID: 25605023). 25605023
EZH2 Y641F diffuse large B-cell lymphoma sensitive GSK126 Preclinical - Cell culture Actionable In a preclinical study, a diffuse large B-cell lymphoma cell line demonstrated sensitivity to GSK126 in culture, resulting in reduced cell viability (PMID: 32906688). 32906688
ARID1A dec exp ovarian cancer sensitive GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 inhibited growth of ovarian cancer cells with knockdown of ARID1A expression in culture (PMID: 25686104). 25686104
EZH2 wild-type melanoma predicted - sensitive GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 inhibited H3K27 trimethylation in human melanoma cells harboring wild-type EZH2 in culture (PMID: 26936398). 26936398
EZH2 Y646N melanoma sensitive GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 treatment inhibited cell growth via suppression of downstream tumor suppressor gene targets and induced apoptosis in melanoma cells harboring EZH2 Y646N in culture (PMID: 26304929). 26304929
EZH2 Y111D EZH2 A677G Advanced Solid Tumor resistant GSK126 Preclinical - Cell culture Actionable In a preclinical study, transformed cells overexpressing EZH2 and carrying simultaneous A677G and Y111D mutations were resistant to GSK126 in culture (PMID: 26360609). 26360609
KDM6A loss multiple myeloma sensitive GSK126 Preclinical - Cell line xenograft Actionable In a preclinical study, a multiple myeloma cell line demonstrated sensitivity to treatment with GSK126, resulting in decreased viability in culture and decreased tumor growth in xenograft models (PMID: 29045832). 29045832
KDM6A loss bladder urothelial carcinoma sensitive GSK126 Preclinical - Cell culture Actionable In a preclinical study, KDM6A-null urothelial bladder carcinoma cell lines demonstrated sensitivity to GSK126, resulting in decreased proliferation in culture (PMID: 28228601). 28228601
ARID1A mut PIK3CA act mut ovarian cancer sensitive GSK126 Preclinical - Cell culture Actionable In a preclinical study, expression of a constitutively active PIK3CA mutation in ARID1A-mutant ovarian cancer cell lines enhanced growth inhibition by GSK126 in culture (PMID: 25686104). 25686104

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 Covered Countries Other Countries
NCT02082977 Phase I GSK126 A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK2816126 in Subjects With Relapsed/Refractory Diffuse Large B Cell and Transformed Follicular Lymphoma Terminated USA 2


Additional content available in CKB BOOST