Reference Detail


Missing content? – Request curation!

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

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

Email us at :

Ref Type Journal Article
PMID (28892380)
Authors Romero FA, Murray J, Lai KW, Tsui V, Albrecht BK, An L, Beresini MH, de Leon Boenig G, Bronner SM, Chan EW, Chen KX, Chen Z, Choo EF, Clagg K, Clark K, Crawford TD, Cyr P, de Almeida Nagata D, Gascoigne KE, Grogan JL, Hatzivassiliou G, Huang W, Hunsaker TL, Kaufman S, Koenig SG, Li R, Li Y, Liang X, Liao J, Liu W, Ly J, Maher J, Masui C, Merchant M, Ran Y, Taylor AM, Wai J, Wang F, Wei X, Yu D, Zhu BY, Zhu X, Magnuson S
Title GNE-781, A Highly Advanced Potent and Selective Bromodomain Inhibitor of Cyclic Adenosine Monophosphate Response Element Binding Protein, Binding Protein (CBP).
Journal Journal of medicinal chemistry
Vol 60
Issue 22
Date 2017 Nov 22
Abstract Text Inhibition of the bromodomain of the transcriptional regulator CBP/P300 is an especially interesting new therapeutic approach in oncology. We recently disclosed in vivo chemical tool 1 (GNE-272) for the bromodomain of CBP that was moderately potent and selective over BRD4(1). In pursuit of a more potent and selective CBP inhibitor, we used structure-based design. Constraining the aniline of 1 into a tetrahydroquinoline motif maintained potency and increased selectivity 2-fold. Structure-activity relationship studies coupled with further structure-based design targeting the LPF shelf, BC loop, and KAc regions allowed us to significantly increase potency and selectivity, resulting in the identification of non-CNS penetrant 19 (GNE-781, TR-FRET IC50 = 0.94 nM, BRET IC50 = 6.2 nM; BRD4(1) IC50 = 5100 nΜ) that maintained good in vivo PK properties in multiple species. Compound 19 displays antitumor activity in an AML tumor model and was also shown to decrease Foxp3 transcript levels in a dose dependent manner.


  • 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"


  • 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 Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
GNE-781 GNE-781 is an inhibitor that targets the bromodomain of CREBBP and EP300, which results in suppression of Myc, and subsequently, may lead to antitumor activity (PMID: 28892380, PMID: 32371576).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown acute myeloid leukemia not applicable GNE-781 Preclinical - Cell line xenograft Actionable In a preclinical study, GNE-781 treatment resulted in tumor growth inhibition and reduced MYC transcript levels in acute myeloid leukemia cell line xenograft models (PMID: 28892380). 28892380