Mivebresib (ABBV-075)

Mivebresib (ABBV-075) is a novel BET family bromodomain inhibitor. It binds bromodomains of BRD2/4/T with similar affinities (Ki of 1-2.2 nM) and highly selective for 18 bromodomain proteins tested (Kd > 1 μM; more than 600-fold selectivity vs. BRD4), but exhibits roughly 10-fold weaker potency towards BRD3 (Ki of 12.2 nM) and has moderate activity towards CREBBP (Kd = 87 μM; 54-fold selectivity vs. BRD4). Mivebresib(ABBV-075) efficiently triggers apoptosis in various tumor cell.

CAS No. 1445993-26-9

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
5mg	JPY 22000	国内在庫あり
25mg	JPY 74500	国内在庫あり
100mg	JPY 220500	国内在庫なし(納期7~10日)
1g	JPY 598500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（10）

製品安全説明書

現在のバッチを見る： S840001 DMSO] 91 mg/mL] false] Water] Insoluble] false] Ethanol] Insoluble] false 純度： 99.97%

99.97

Mivebresib (ABBV-075)関連製品

関連ターゲット	BET p300/CBP BRPF bromodomain	もっと見る
関連製品	ICG-001 Birabresib (OTX015) I-BET151 (GSK1210151A) Molibresib (I-BET-762) SGC-CBP30 EED226 Apabetalone (RVX-208) KG-501 CPI-203 compound 3i (666-15) PFI-3 AZD5153 6-hydroxy-2-naphthoic acid PFI-1 (PF-6405761) ABBV-744 UNC1215 I-BRD9 Bromosporine PLX51107 GSK1324726A (I-BET726) Pelabresib (CPI-0610) PF-CBP1 HCl INCB054329 MS436 GSK2801 UNC669 MZ-1 NEO2734 OF-1 CPI-637 GSK6853 I-CBP112 BI-7273 PFI-4 INCB057643 GSK 5959 dBET57 BI-9564 Histone Acetyltransferase Inhibitor II	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library FDA-approved Drug Library Natural Product Library Bioactive Compound Library-I Bioactive Compound Library-Ⅱ	もっと見る

シグナル伝達経路

Epigenetic Reader Domainシグナル伝達経路

Epigenetic Reader Domain阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
SKM1	Antitumor assay	60 mg/kg		Antitumor activity against human SKM1 cells xenografted in SCID mouse assessed as tumor growth inhibition at 60 mg/kg, po bid by caliper method	32324999
MV4-11	Antiproliferative assay		72 hrs	Antiproliferative activity against human MV4-11 cells assessed as reduction in cell viability measured after 72 hrs by Celltitre-glo luminescence assay, IC50=0.0019μM.	32208600
Kasumi-1	Antiproliferative assay		72 hrs	Antiproliferative activity against human Kasumi-1 cells assessed as reduction in cell viability measured after 72 hrs by Celltitre-glo luminescence assay, IC50=0.0063μM.	32208600
RS4:11	Antiproliferative assay		72 hrs	Antiproliferative activity against human RS4:11 cells assessed as reduction in cell viability measured after 72 hrs by Celltitre-glo luminescence assay, IC50=0.0064μM.	32208600
MM1S	Antiproliferative assay		72 hrs	Antiproliferative activity against human MM1S cells assessed as reduction in cell viability measured after 72 hrs by Celltitre-glo luminescence assay, IC50=0.0065μM.	32208600
MX1	Antiproliferative assay		72 hrs	Antiproliferative activity against human MX1 cells incubated for 72 hrs by cell-titer Glo assay, EC50=0.013μM.	29678460
MX1	Antiproliferative assay		72 hrs	Antiproliferative activity against human MX1 cells after 72 hrs by Cell Titer Glo assay, EC50=0.013μM.	28949521
H1299	Function assay		24 hrs	Binding affinity to BRD4 in human H1299 cells stably expressing E2 and HPV16-LCR luciferase reporter incubated for 24 hrs by Bright-Glo luciferase reporter gene assay based BRD4 engagement assay, IC50=0.02μM.	29678460
H1299	Function assay		24 hrs	Inhibition of BRD4 in human H1299 cells assessed as decrease in HPV LCR-E2-EP400-mediated transcriptional repression after 24 hrs by Bright-Glo luciferase reporter gene assay, EC50=0.02μM.	28949521
MV411	Antiproliferative assay		72 hrs	Antiproliferative activity against BRD4-sensitive human MV411 cells after 72 hrs by CCK8 assay, IC50=0.07μM.	28314513
HL60	Antiproliferative assay		72 hrs	Antiproliferative activity against BRD4-sensitive human HL60 cells after 72 hrs by CCK8 assay, IC50=0.09μM.	28314513
insect cells	Function assay			Inhibition of recombinant full length human N-terminal His6-tagged BRD4 (2 to 1362 residues) expressed in baculovirus infected insect cells using histone H4 peptide as substrate by alpha screen assay, IC50=0.02μM.	30529546
HL60	Antiproliferative assay			Antiproliferative activity against human HL60 cells assessed as reduction in cell viability by MTT assay, IC50=0.12μM.	31857846
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

Mivebresib (ABBV-075) is a novel BET family bromodomain inhibitor. It binds bromodomains of BRD2/4/T with similar affinities (Ki of 1-2.2 nM) and highly selective for 18 bromodomain proteins tested (Kd > 1 μM; more than 600-fold selectivity vs. BRD4), but exhibits roughly 10-fold weaker potency towards BRD3 (Ki of 12.2 nM) and has moderate activity towards CREBBP (Kd = 87 μM; 54-fold selectivity vs. BRD4). Mivebresib(ABBV-075) efficiently triggers apoptosis in various tumor cell.

Targets

BRD2 ^[1]

BRD4 ^[1]

BRD-T ^[1]

In Vitro
In vitro	ABBV-075 exhibits robust single agent activity in cell viability assays across cancer cell lines derived from solid tumors, leukemia and lymphomas. It could disrupt cell cycle control leading to G1 arrest followed by senescence, inhibit oncogenesis drivers leading to apoptosis, and potentially target tumor microenvironment to provide additional therapeutic benefit^[1].
細胞実験	細胞株	Macrophages
	濃度	0.1 µM
	反応時間	48 h
	実験の流れ	Cells were treated with indicated concentration of drug for 48 h.
実験結果図	Methods	Biomarkers	結果図	PMID
実験結果図	Western blot	BRD4 / c-Myc / CDK6 / Bcl-xL / Bcl-2 / Mcl-1 / HEXIM1 / p21 / p27 / Cleaved PARP		30647404

In Vivo
In Vivo	ABBV-075 has comparable or superior efficacies to standard of care agents in flank xenograft mouse models of non-small-cell and small cell lung cancers, pancreatic, breast, prostate, head & neck cancers, multiple myeloma, diffuse large B cell lymphoma and leukemia^[1].

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT04480086	Terminated	Myelofibrosis (MF)	AbbVie	March 17 2021	Phase 1
NCT02391480	Completed	Cancer\|Breast Cancer\|Non-Small Cell Lung Cancer\|Acute Myeloid Leukemia (AML)\|Multiple Myeloma\|Prostate Cancer\|Small Cell Lung Cancer\|Non-Hodgkins Lymphoma	AbbVie	April 14 2015	Phase 1

参考
[1] Aparna Sarthy, et al. Experimental and Molecular Therapeutics. 2016, Abstract 4718. [2] Wu Y, et al. J Cancer Res Clin Oncol. 2022 Apr;148(4):803-821.

参考

化学情報

分子量	459.47	化学式	C₂₂H₁₉F₂N₃O₄S
CAS No.	1445993-26-9	SDF	Download Mivebresib (ABBV-075) SDFをダウンロードする
Smiles	CCS(=O)(=O)NC1=CC(=C(C=C1)OC2=C(C=C(C=C2)F)F)C3=CN(C(=O)C4=C3C=CN4)C
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 91 mg/mL ( (198.05 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):