Home Epigenetics BET inhibitor Mivebresib (ABBV-075)

연구용

Mivebresib (ABBV-075) BET Inhibitor

제품 번호: S8400

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.
Mivebresib (ABBV-075) BET inhibitor Chemical Structure

화학 구조

분자량: 459.47

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품질 관리 (Quality Control)

배치: 순도: 99.97%
99.97

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
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
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
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
HL60 Antiproliferative assay Antiproliferative activity against human HL60 cells assessed as reduction in cell viability by MTT assay, IC50=0.12μM. 31857846
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
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 459.47 화학식

C22H19F2N3O4S

 보관 (수령일로부터)
CAS 번호 1445993-26-9 SDF 다운로드 원액 보관

동의어 N/A 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

용해도 (Solubility)

In vitro
배치:

DMSO : 91 mg/mL (198.05 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

mg/kg g μL

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH2O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

Targets/IC50/Ki
BRD2
BRD4
BRD-T
시험관 내(In vitro)

Mivebresib (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.
생체 내(In vivo)

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, Mivebresib (ABBV-075) has comparable or superior efficacies to standard of care agents.
참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot BRD4 / c-Myc / CDK6 / Bcl-xL / Bcl-2 / Mcl-1 / HEXIM1 / p21 / p27 / Cleaved PARP
S8400-WB1
30647404

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2024-05-22)

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
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