Name: Mivebresib
Brand: BOC Sciences
Price: 719 USD
Availability: MadeToOrder

Purity

98%

Solubility

Soluble in DMSO

Appearance

Powder

Application

anti-tumor

ShelfLife

2 month in rt, long time

Storage

-20°C Freezer

IUPACName

N-[4-(2,4-difluorophenoxy)-3-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)phenyl]ethanesulfonamide

Synonyms

ABBV-075; ABBV 075; ABBV075; Mivebresib;N-(4-(2,4-difluorophenoxy)-3-(6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenyl)ethanesulfonamide

InChI Key

RDONXGFGWSSFMY-UHFFFAOYSA-N

InChI

1S/C22H19F2N3O4S/c1-3-32(29,30)26-14-5-7-19(31-20-6-4-13(23)10-18(20)24)16(11-14)17-12-27(2)22(28)21-15(17)8-9-25-21/h4-12,25-26H,3H2,1-2H3

SMILES

CCS(=O)(=O)Nc1ccc(Oc2ccc(F)cc2F)c(c1)C3=CN(C)C(=O)c4[nH]ccc34

Mechanism

Target: This ligand targets BET-family bromodomains, including BRD2, BRD3, BRD4, and BRDT in biochemical or cellular target-engagement studies.

Mechanism of Action: Used as the target-protein recognition element, this ligand provides the binding interface for BET-family bromodomains, including BRD2, BRD3, BRD4, and BRDT. In PROTAC design, a derivatizable position on the ligand can be connected through an optimized linker to an E3 ligase ligand, such as a CRBN, VHL, or IAP recruiter, while preserving productive target engagement. The resulting bifunctional molecule brings BET-family bromodomains into proximity with the recruited E3 ligase, enabling ternary-complex formation. If the complex has favorable geometry and residence time, target lysine ubiquitination is promoted, leading to proteasome-dependent degradation in experimental systems.

Applications

• BET-Bromodomain Degradation PROTAC: Mivebresib can be leveraged as a BET-bromodomain-binding ligand within PROTAC constructs to recruit an E3 ligase and drive selective degradation of BET family proteins. This application supports mechanistic studies of chromatin reader removal, enabling assessment of downstream transcriptional programs and resistance pathways in cancer-relevant models.

• Transcriptional Dependency Mapping: Incorporating Mivebresib into PROTACs enables systematic interrogation of how BET protein depletion reshapes gene expression networks. By comparing degradation potency across BET targets, researchers can map transcriptional dependencies, identify biomarkers linked to degradation sensitivity, and refine target engagement strategies using proteomics and reporter-based assays.

• E3 Ligase Recruitment Optimization: Mivebresib-based PROTACs can be designed with different E3 ligase recruiters to evaluate how ligase choice influences ternary complex formation and degradation efficiency. This direction supports optimization of linker length, attachment chemistry, and cooperativity to maximize on-target proteolysis while minimizing off-target effects.

• Resistance Mechanism Investigation: PROTAC-mediated degradation using a Mivebresib ligand provides a platform to study therapeutic resistance mechanisms distinct from BET inhibition. Researchers can evaluate whether forced BET protein removal circumvents adaptive signaling or compensatory transcriptional rewiring, using longitudinal cell line studies and degradation kinetics profiling.

• Targeted Epigenetic Remodeling Studies: Mivebresib-containing PROTACs can be used to dissect the causal role of BET protein presence in epigenetic regulation. Selective degradation allows researchers to distinguish effects of bromodomain occupancy from those of protein loss, supporting chromatin accessibility and histone-mark dynamics studies in controlled experimental systems.

1.BET inhibition in advanced cutaneous T cell lymphoma is synergistically potentiated by BCL2 inhibition or HDAC inhibition.

Kim SR;Lewis JM;Cyrenne BM;Monico PF;Mirza FN;Carlson KR;Foss FM;Girardi M Oncotarget. 2018 Jun 26;9(49):29193-29207. doi: 10.18632/oncotarget.25670. eCollection 2018 Jun 26.

While several systemic therapies are approved for cutaneous T cell lymphoma (CTCL), a non-Hodgkin lymphoma of skin-homing T cells that may involve lymph nodes and peripheral blood in advanced stages, relapses are common. Mutational analysis of CTCL cells has revealed frequent amplification of the ;MYC; oncogene, and bromodomain and extraterminal (BET) protein inhibitors have been shown to repress MYC expression in various malignancies. Towards a potential novel therapy, we thus sought to examine the effect of BET inhibition on CTCL cells ;in vitro;. Each of the four tested BET inhibitors (JQ1, ABBV-075, I-BET762, CPI-0610) consistently induced dose-dependent decreases in viability of isolated patient-derived CTCL cells and established CTCL cell lines (MyLa, Sez4, HH, Hut78). This effect was synergistically potentiated by combination of BET inhibition with BCL2 inhibition (e.g. venetoclax) or histone deacetylase (HDAC) inhibition (e.g. vorinostat or romidepsin). There was also a marked increase in caspase 3/7 activation when JQ1 was combined with either vorinostat or romidepsin, confirming that the observed synergies are due in major part to induction of apoptosis. Furthermore, ;MYC; and ;BCL2; expression were each synergistically repressed when CTCL cells were treated with JQ1 plus HDAC inhibitors, suggesting cooperative activities at the level of epigenetic regulation.

2.Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies.

Bui MH;Lin X;Albert DH;Li L;Lam LT;Faivre EJ;Warder SE;Huang X;Wilcox D;Donawho CK;Sheppard GS;Wang L;Fidanze S;Pratt JK;Liu D;Hasvold L;Uziel T;Lu X;Kohlhapp F;Fang G;Elmore SW;Rosenberg SH;McDaniel KF;Kati WM;Shen Y Cancer Res. 2017 Jun 1;77(11):2976-2989. doi: 10.1158/0008-5472.CAN-16-1793. Epub 2017 Apr 17.

ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently entered phase I clinical trials. Comprehensive preclinical characterization of ABBV-075 demonstrated broad activity across cell lines and tumor models, representing a variety of hematologic malignancies and solid tumor indications. In most cancer cell lines derived from solid tumors, ABBV-075 triggers prominent G;1; cell-cycle arrest without extensive apoptosis. In this study, we show that ABBV-075 efficiently triggers apoptosis in acute myeloid leukemia (AML), non-Hodgkin lymphoma, and multiple myeloma cells. Apoptosis induced by ABBV-075 was mediated in part by modulation of the intrinsic apoptotic pathway, exhibiting synergy with the BCL-2 inhibitor venetoclax in preclinical models of AML. In germinal center diffuse large B-cell lymphoma, BCL-2 levels or venetoclax sensitivity predicted the apoptotic response to ABBV-075 treatment. ;In vivo; combination studies uncovered surprising benefits of low doses of ABBV-075 coupled with bortezomib and azacitidine treatment, despite the lack of ;in vitro; synergy between ABBV-075 and these agents. The ;in vitro;/;in vivo; activities of ABBV-075 described here may serve as a useful reference to guide the development of ABBV-075 and other BET family inhibitors for cancer therapy.

3.Discovery of N-(4-(2,4-Difluorophenoxy)-3-(6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenyl)ethanesulfonamide (ABBV-075/Mivebresib), a Potent and Orally Available Bromodomain and Extraterminal Domain (BET) Family Bromodomain Inhibitor.

McDaniel KF;Wang L;Soltwedel T;Fidanze SD;Hasvold LA;Liu D;Mantei RA;Pratt JK;Sheppard GS;Bui MH;Faivre EJ;Huang X;Li L;Lin X;Wang R;Warder SE;Wilcox D;Albert DH;Magoc TJ;Rajaraman G;Park CH;Hutchins CW;Shen JJ;Edalji RP;Sun CC;Martin R;Gao W;Wong S;Fang G;Elmore SW;Shen Y;Kati WM J Med Chem. 2017 Oct 26;60(20):8369-8384. doi: 10.1021/acs.jmedchem.7b00746. Epub 2017 Oct 12.

The development of bromodomain and extraterminal domain (BET) bromodomain inhibitors and their examination in clinical studies, particularly in oncology settings, has garnered substantial recent interest. An effort to generate novel BET bromodomain inhibitors with excellent potency and drug metabolism and pharmacokinetics (DMPK) properties was initiated based upon elaboration of a simple pyridone core. Efforts to develop a bidentate interaction with a critical asparagine residue resulted in the incorporation of a pyrrolopyridone core, which improved potency by 9-19-fold. Additional structure-activity relationship (SAR) efforts aimed both at increasing potency and improving pharmacokinetic properties led to the discovery of the clinical candidate 63 (ABBV-075/mivebresib), which demonstrates excellent potency in biochemical and cellular assays, advantageous exposures and half-life both in animal models and in humans, and in vivo efficacy in mouse models of cancer progression and inflammation.

ConcentrationVolumeMass	1 mg	5 mg	10 mg
1 mM	2.1764 mL	10.8821 mL	21.7642 mL
5 mM	0.4353 mL	2.1764 mL	4.3528 mL
10 mM	0.2176 mL	1.0882 mL	2.1764 mL
50 mM	0.0435 mL	0.2176 mL	0.4353 mL

Mivebresib is a bromodomain ligand scaffold that may support bromodomain-directed PROTAC design. Linker installation should preserve the pyrrolopyridinone-like recognition core and sulfonamide features.

Structure: Mivebresib is a bromodomain ligand containing a pyrrolopyridinone-like heteroaryl core, difluorophenoxy aryl substituent, and ethanesulfonamide group. The structure is heteroatom-rich and includes sulfonamide hydrogen-bonding functionality and fluorinated aromatic groups.

Reactivity: For bromodomain-directed PROTAC design, the heteroaryl recognition core and sulfonamide pharmacophore should be preserved. Linker installation is most plausibly explored from a peripheral aryl ether, sulfonamide-associated, or solvent-exposed vector in a linker-ready analog. Alkyl, PEG, amide, sulfonamide-compatible, or carbamate linkers may be joined to CRBN, VHL, or IAP ligands after validating that bromodomain binding is retained.

Dear Sir, I'd like to know which apart does it bind to BRD-containing proteins.

Mivebresib binds to the acetyl-lysine binding site in the BRD of certain BRD-containing proteins, thereby preventing the interaction between those proteins and acetylated histones.

21/3/2016

Dear Sir, please give information about how Mivebresib alleviates systemic lupus erythematosus-associated diffuse alveolar hemorrhage.

Mivebresib alleviates systemic lupus erythematosus-associated diffuse alveolar hemorrhage via inhibiting infiltration of monocytes and M1 polarization of macrophages.

3/4/2016

Hello, how does Mivebresib induce apoptosis in bladder cancer cells?

Mivebresib induces apoptosis in bladder cancer cells via the mitochondrial pathway.

3/5/2017

Hello, I want to know that how many parts can its structure be divided into.

It can be divided into ZA channel,Kac region, and WPF region.

29/3/2020

Dear team, I would like to know the progress of its clinical research.

Phase 1b Study of Mivebresib is underway.

30/4/2021

Do you have any information about how Mivebresib protects C57BL/6J mice against pristane-induced DAH?

Mivebresib effectively protected C57BL/6J mice against pristane-induced DAH by inhibiting the migration and polarization of monocytes and macrophages, as well as pathogenic B and T cells.

21/5/2023

inhibit DHT-stimulated transcription of AR target genes

As we hoped, Mivebresib inhibit DHT-stimulated transcription of AR target genes without significant effect on AR protein expression, which is great for our research.

23/9/2016

inhibit LPS-induced M1 polarization of macrophages

In vitro experiments demonstrated that Mivebresib inhibited LPS-induced M1 polarization of macrophages and the expression of pro-inflammatory cytokines, M1 marker genes, and chemokines-chemokine receptors while thwarting the secretion of IL-6 and TNF-α. It's very useful for our project!

3/8/2017

modify the distribution of leukocytes

Our results revealed that Mivebresib effectively modified the distribution of leukocytes, impeded the polarization of inflammatory macrophages, and reduced the frequency of CD19 + CD5 + B cells in the lungs of pristane-treated mice. Great performance.

27/11/2017

reduce the proportion of monocytes

Our flow cytometry analysis showed that Mivebresib considerably reduced the proportion of monocytes in myeloid cells.

3/12/2018

change T cell composition

We investigated that Mivebresib did result in significant expansion of CD4-CD8 + T cells and a reduction in CD4 + T cells, resulting in the former becoming the dominant subset.

13/4/2019

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