Mivebresib | ABBV-075 | CAS#1445993-26-9 | BET inhibitor

MedKoo Cat#: 206520 | Name: Mivebresib

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Mivebresib, also known as ABBV-075, is a potent BET inhibitor (bromodomain (BRD)-containing proteind) with potential antineoplastic activity. Upon administration, the bromodomain inhibitor ABBV-075 binds to the acetyl-lysine binding site in the BRD of certain BRD-containing protein(s), thereby preventing the interaction between those proteins and acetylated histones. This disrupts chromatin remodeling, prevents the expression of certain growth-promoting genes, and leads to an inhibition of cell growth in susceptible tumors.

Chemical Structure

Mivebresib

CAS#1445993-26-9

Theoretical Analysis

MedKoo Cat#: 206520

Name: Mivebresib

CAS#: 1445993-26-9

Chemical Formula: C22H19F2N3O4S

Exact Mass: 459.1064

Molecular Weight: 459.47

Elemental Analysis: C, 57.51; H, 4.17; F, 8.27; N, 9.15; O, 13.93; S, 6.98

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,850.00	Ready to Ship
1g	USD 4,250.00	Ready to Ship
2g	USD 6,450.00	Ready to Ship

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Related CAS #

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Synonym

ABBV-075; ABBV 075; ABBV075; Mivebresib

IUPAC/Chemical Name

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 Code

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 Code

CCS(=O)(NC1=CC=C(OC2=CC=C(F)C=C2F)C(C3=CN(C)C(C4=C3C=CN4)=O)=C1)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#CRB70314

QC Data

View QC data: current batch, Lot#CRB70314

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Mivebresib (ABBV-075) is a potent bromodomain and extraterminal domain (BET) bromodomain inhibitor that binds to BRD4 with a Ki of 1.5 nM

In vitro activity:

To determine whether the noted apoptotic response to ABBV-075 can be recapitulated in primary patient-derived samples, we focused on AML, where patient-derived cells are readily available. Similar to what was observed in AML cell lines, patient-derived AML cells were also highly sensitive to ABBV-075 (IC50 < 0.1 μmol/L), and eight out of nine patient samples exhibited >30% apoptosis (Fig. 3D). It is noteworthy that many patient-derived AML cells appeared to be resistant to cytarabine, a first-line therapy for AML (e.g., pts 3027, 3235, 3012, and 3085, all with IC50s ≥ 3 μmol/L), but remained responsive to ABBV-075, suggesting that ABBV-075 may provide benefit in the resistant/refractory setting of AML. As controls, no high degrees of apoptosis was observed in PBMCs from healthy donors, and ABBV-075 or MS417 did not trigger apoptosis in CD34+ cells from cord blood (Supplementary Fig. S3). ABBV-075 also downregulated both BCL-XL and BCL-2 in SKM-1 cells and downregulated BCL-XL in AML-2 and OCI-Ly3 cells (Supplementary Fig. S5), indicating that modulating the intrinsic apoptotic machinery may be a common mechanism underlying apoptosis induced by BET inhibitors. Reference: Cancer Res. 2017 Jun 1;77(11):2976-2989. https://pubmed.ncbi.nlm.nih.gov/28416490/

In vivo activity:

To identify potential pharmacodynamic markers for BET inhibitors in skin, we determined transcriptional alterations in skin samples from ABBV-075–treated mice. Hexim1 and Lrg1 were significantly up- or downregulated, respectively, in skin samples from ABBV075–treated mice (Supplementary Fig. S4). Similar to what was observed in tumor and blood, Hexim1 was upregulated by ABBV-075 at 6 hours and returned to baseline at 24 hours (Fig. 5A). ABBV-075 treatment caused significant upregulation of Hexim1 but not the housekeeping genes B2m and Hprt1 in these FFPE samples (Fig. 5B). The response of Hexim1 to ABBV-075 in FFPE skin samples was further verified using the RNA ISH method. As shown in Fig. 5C, ABBV-075 treatment resulted in a significant increase of Hexim1 expression in the skin section. Reference: Mol Cancer Ther. 2017 Feb;16(2):388-396. https://pubmed.ncbi.nlm.nih.gov/27903752

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	60.0	130.59

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 459.47 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. 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. Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies. Cancer Res. 2017 Jun 1;77(11):2976-2989. doi: 10.1158/0008-5472.CAN-16-1793. Epub 2017 Apr 17. PMID: 28416490. 2. Faivre EJ, Wilcox D, Lin X, Hessler P, Torrent M, He W, Uziel T, Albert DH, McDaniel K, Kati W, Shen Y. Exploitation of Castration-Resistant Prostate Cancer Transcription Factor Dependencies by the Novel BET Inhibitor ABBV-075. Mol Cancer Res. 2017 Jan;15(1):35-44. doi: 10.1158/1541-7786.MCR-16-0221. Epub 2016 Oct 5. PMID: 27707886. 3. Lin X, Huang X, Uziel T, Hessler P, Albert DH, Roberts-Rapp LA, McDaniel KF, Kati WM, Shen Y. HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues. Mol Cancer Ther. 2017 Feb;16(2):388-396. doi: 10.1158/1535-7163.MCT-16-0475. Epub 2016 Nov 30. PMID: 27903752.

In vitro protocol:

In vivo protocol:

1. Lin X, Huang X, Uziel T, Hessler P, Albert DH, Roberts-Rapp LA, McDaniel KF, Kati WM, Shen Y. HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues. Mol Cancer Ther. 2017 Feb;16(2):388-396. doi: 10.1158/1535-7163.MCT-16-0475. Epub 2016 Nov 30. PMID: 27903752. 2. Faivre EJ, Wilcox D, Lin X, Hessler P, Torrent M, He W, Uziel T, Albert DH, McDaniel K, Kati W, Shen Y. Exploitation of Castration-Resistant Prostate Cancer Transcription Factor Dependencies by the Novel BET Inhibitor ABBV-075. Mol Cancer Res. 2017 Jan;15(1):35-44. doi: 10.1158/1541-7786.MCR-16-0221. Epub 2016 Oct 5. PMID: 27707886.