I am a Healthcare Professional outside the US and UK

I am a Healthcare Professional outside the US and UK

Click here for international medical scientific information about Oncology for Healthcare Professionals.

I am not a Healthcare Professional and I am outside the US and the UK

I am not a Healthcare Professional and I am outside the US and the UK

Click here for general international information for patients, caregivers and the general public.

Country-specific medical scientific information

Country-specific medical scientific information

Country-specific medical scientific information for Healthcare Professionals.

This site uses cookies to improve your browsing experience. By using this site, you agree to their use. Cookie Information


BET inhibitor (BI 894999)

BI 894999: A selective inhibitor of the BET family

BI 894999* is an oral, potent and selective inhibitor of the bromodomain and extra-terminal (BET) family of bromodomain (BDR)-containing proteins.1–3 It is currently being investigated in a Phase I clinical trial in patients with advanced solid tumours.4

About BET proteins

BRD proteins are chromatin ‘readers’. They bind to and interpret post-translational modifications added by epigenetic ‘writers’ or removed by epigenetic ‘erasers’ and thereby regulate gene expression.5,6

BRD4 is a member of the BET family and is considered to be a key epigenetic regulator.1,2 It controls a subset of genes by recognising key regulatory elements and indirectly modulating essential transcription factors, such as c-Myc and E2F.5 BRD4 deregulation is implicated in a number of haematological malignancies and solid tumours.6–11

BI 894999’s mechanism of action

BI 894999 is an oral inhibitor of the BET family of BRD-containing proteins that bind to acetylated histones inducing transcription.1–3,12

BI 894999 inhibits BRD4 (as well as BRD2, BRD3 and BRDT) with high selectivity and potency, 1–3,12 triggering suppression of target gene transcription (e.g. the oncogene Myc). 5,6,13

BI 894999’s mechanism of action2

BI 894999 BET inhibitor mechanism of action

BET, bromodomain and extra-terminal domain; BRD4, bromodomain protein 4; CDK9, cyclin-dependent kinase 9; CTD, C-terminal domain; P, phosphate; mRNA, messenger ribonucleic acid.

Preclinical and clinical development

BI 894999 has shown high in vitro and in vivo activity in multiple myeloma, acute myeloid leukaemia and solid tumours.1–3

Initial data from a Phase I study (1367.1) of BI 894999 demonstrated clinical activity and a manageable safety profile in patients with solid tumours.3 It also established the maximum tolerated dose for continuous dosing.3 Further investigations of BI 894999 are now underway in patients with advanced, unresectable and/or metastatic solid tumours that have failed on, or are unsuitable for, conventional treatment.4

Solid tumours


BET, bromodomain and extra-terminal domain; BOR, best overall response; CR,  complete reponse; DLT, dose-limiting toxicity; MTD, maximum tolerated dose; ORR, objective response; PFS, progression-free survival; PK, pharmacokinetics; PR, partial response; PSA, prostate-specific antigen.

Did you find this information useful?



Tontsch-Grunt U, et al. Poster presented at AACR-NCI-EORTC 2015 (Abstract B79).


Tontsch-Grunt U, et al. J Clin Oncol 2016;34(Suppl. 15):11574.


Aftimos PG, et al. J Clin Oncol 2017;35(Suppl. 15):2504.


ClinicalTrials.gov. NCT02516553. https://clinicaltrials.gov/ct2/show/record/NCT02516553 (Accessed: April 2019).


Jung M, et al. Epigenomics 2015;7(3):487–501.


Zuber J, et al. Nature 2011;478(7370):524–8.


Fu LL, et al. Oncotarget 2015;6:5501–16.


Xu Y, Vakoc CR. Cold Spring Harb Perspect Med 2017;7:pii: a026674.


Filippakopoulos P, et al. Nature 2010;468:1067–73.


Delmore JE, et al. Cell 2011;146:904–17.


Shi J, Vakoc C. Molecular Cell 2014;54:728–36; 6.


Doroshow DB, et al. Ann Oncol 2017;28:1776–87.


Gerlach D, et al. Oncogene 2018;37(20):2687–701

You may also be interested in

*This is an investigational compound and has not been approved. Its safety and efficacy have not been established.


© 2019 Boehringer Ingelheim International GmbH. All rights reserved.

Page last updated: July 2019