연구용

Molibresib (I-BET-762) BET 억제제

제품 번호S7189

Molibresib (I-BET-762, GSK525762, GSK525762A)는 무세포 분석에서 ~35 nM의 IC50을 가진 BET 단백질 억제제입니다. 이는 대식세포에 의한 전염증성 단백질 생산을 억제하고 급성 염증을 차단하며, 다른 브로모도메인 함유 단백질에 비해 높은 선택성을 보입니다.
Molibresib (I-BET-762) BET 억제제 Chemical Structure

화학 구조

분자량: 423.9

바로가기

품질 관리

배치: 순도: 99.87%
99.87

세포 배양, 처리 및 작업 농도

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
HepG2 Function assay 18 hrs Induction of human ApoA1 gene expression in stably transfected human HepG2 cells coexpressing luciferase reporter gene after 18 hrs by luminescence assay, EC50 = 0.7 μM. 21568322
HepG2 Function assay 6 hrs Induction of human ApoA1 protein synthesis in human HepG2 cells assessed as neosynthesised radiolabeled protein secretion after 6 hrs by SDS PAGE analysis in presence of [35S]methionine 21568322
HepG2 Function assay 18 hrs Upregulation of ApoA1 expression in human HepG2 cells assessed as concentration required to increase 70% of luciferase activity after 18 hrs by luciferase reporter gene assay, EC170 = 0.2 μM. 22386529
HepG2 Function assay 18 hrs Induction of human ApoA1 gene expression in stably transfected human HepG2 cells coexpressing luciferase reporter gene after 18 hrs by luminescence assay, EC50 = 0.7 μM. 22924434
PBMC Antiinflammatory assay Antiinflammatory activity against human PBMC cells assessed as LPS-induced IL-6 production by chemiluminescence assay, IC50 = 0.31623 μM. 24015967
Raji Function assay 4 hrs Inhibition of BRD4 in human Raji cells assessed as reduction of MYC expression after 4 hrs, IC50 = 0.19 μM. 24900758
Rosetta2 DE3 Function assay 30 mins Displacement of FAM-labeled ZBA248 from BRD3 BD2 (306 to 417 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.0303 μM. 26080064
Rosetta2 DE3 Function assay 30 mins Displacement of FAM-labeled ZBA248 from BRD4 BD2 (333 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.0323 μM. 26080064
Rosetta2 DE3 Function assay 30 mins Displacement of FAM-labeled ZBA248 from BRD4 BD1 (44 to 168 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.0388 μM. 26080064
Rosetta2 DE3 Function assay Binding affinity to biotinylated BRD3 BD2 (306 to 417 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.0407 μM. 26080064
Rosetta2 DE3 Function assay Binding affinity to biotinylated BRD2 BD2 (349 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.0454 μM. 26080064
Rosetta2 DE3 Function assay Binding affinity to biotinylated BRD4 BD2 (333 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.0476 μM. 26080064
Rosetta2 DE3 Function assay 30 mins Displacement of FAM-labeled ZBA248 from BRD2 BD2 (349 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.0492 μM. 26080064
Rosetta2 DE3 Function assay 30 mins Displacement of FAM-labeled ZBA248 from BRD3 BD1 (24 to 144 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.0539 μM. 26080064
Rosetta2 DE3 Function assay 30 mins Displacement of FAM-labeled ZBA248 from BRD2 BD1 (72 to 205 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.0568 μM. 26080064
Rosetta2 DE3 Function assay Binding affinity to biotinylated BRD3 BD1 (24 to 144 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.0607 μM. 26080064
MV4-11 Cytotoxicity assay 4 days Cytotoxicity against human MV4-11 cells harboring MLL1 fusion gene assessed as growth inhibition after 4 days by CellTiter-Glo luminescent assay, IC50 = 0.093 μM. 26080064
Rosetta2 DE3 Function assay 30 mins Displacement of FAM-labeled ZBA248 from BRD4 BD2 (333 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, IC50 = 0.0984 μM. 26080064
Rosetta2 DE3 Function assay Binding affinity to biotinylated BRD4 BD1 (44 to 168 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.0994 μM. 26080064
Rosetta2 DE3 Function assay 30 mins Displacement of FAM-labeled ZBA248 from BRD4 BD1 (44 to 168 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, IC50 = 0.156 μM. 26080064
Rosetta2 DE3 Function assay Binding affinity to biotinylated BRD2 BD1 (72 to 205 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.159 μM. 26080064
MOLM13 Cytotoxicity assay 4 days Cytotoxicity against human MOLM13 cells harboring MLL1 fusion gene assessed as growth inhibition after 4 days by CellTiter-Glo luminescent assay, IC50 = 0.241 μM. 26080064
BL21(DE3) Function assay Binding affinity to N-terminal His6-tagged-BRD4 bromodomain 2 (unknown origin) expressed in competent Escherichia coli BL21(DE3) cells by isothermal titration calorimetry, Kd = 0.065 μM. 26367539
BL21(DE3) Function assay Binding affinity to N-terminal His6-tagged-BRD4 bromodomain 1 (unknown origin) expressed in competent Escherichia coli BL21(DE3) cells by isothermal titration calorimetry, Kd = 0.095 μM. 26367539
BL21(DE3) Function assay Binding affinity to full length N-terminal His6-tagged-BRD2 bromodomain 2 (unknown origin) expressed in competent Escherichia coli BL21(DE3) cells by isothermal titration calorimetry, Kd = 0.1 μM. 26367539
BL21(DE3) Function assay Binding affinity to full length N-terminal His6-tagged-BRD2 bromodomain 1 (unknown origin) expressed in competent Escherichia coli BL21(DE3) cells by isothermal titration calorimetry, Kd = 0.23 μM. 26367539
BL21(DE3)-R3-pRARE2 Function assay Inhibition of human His-tagged BRD4 bromodomain 2 expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by FRET assay, IC50 = 0.036 μM. 26731490
BL21(DE3)-R3-pRARE2 Function assay Inhibition of human His-tagged BRD4 bromodomain 1 expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by FRET assay, IC50 = 0.036 μM. 26731490
Rosetta2 DE3 Function assay 30 mins Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay, Ki = 0.023 μM. 28463487
Rosetta2 DE3 Function assay 30 mins Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 1 (44 to 168 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay, Ki = 0.0464 μM. 28463487
Rosetta2 DE3 Function assay 30 mins Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay, IC50 = 0.0775 μM. 28463487
MV4-11 Growth inhibition assay 4 days Growth inhibition of human MV4-11 cells after 4 days by WST-8 assay, IC50 = 0.093 μM. 28463487
Rosetta2 DE3 Function assay 30 mins Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 1 (44 to 168 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay, IC50 = 0.145 μM. 28463487
MOLM13 Growth inhibition assay 4 days Growth inhibition of human MOLM13 cells after 4 days by WST-8 assay, IC50 = 0.241 μM. 28463487
TY82 Antiproliferative assay 72 hrs Antiproliferative activity against human TY82 cells after 72 hrs by CCK8 assay, IC50 = 0.2 μM. 28586718
MM1S Antiproliferative assay 72 hrs Antiproliferative activity against human MM1S cells after 72 hrs by CCK8 assay, IC50 = 0.23 μM. 28586718
BL21 (DE3)-codon plus-RIL Function assay 4 hrs Inhibition of JQ1-FITC binding to His6-tagged BRD4-BD1 (unknown origin) expressed in Escherichia coli BL21 (DE3)-codon plus-RIL cells incubated in dark for 4 hrs by fluorescence anisotropy assay, IC50 = 0.26 μM. 28586718
THP1 Antiproliferative assay Antiproliferative activity against human THP1 cells, IC50 = 0.29 μM. 28939121
TY82 Antiproliferative assay Antiproliferative activity against human TY82 cells, IC50 = 0.39 μM. 28939121
NALM16 Cytotoxicity assay 5 days Cytotoxicity against human NALM16 cells assessed as reduction in cell viability after 5 days by CellTiter-Glo assay, EC50 = 0.27 μM. 29170024
NALM6 Cytotoxicity assay 5 days Cytotoxicity against human NALM6 cells assessed as reduction in cell viability after 5 days by CellTiter-Glo assay, EC50 = 0.39 μM. 29170024
697 Cytotoxicity assay 5 days Cytotoxicity against human 697 cells assessed as reduction in cell viability after 5 days by CellTiter-Glo assay, EC50 = 1.17 μM. 29170024
HD-MB03 Cytotoxicity assay 5 days Cytotoxicity against human HD-MB03 cells assessed as reduction in cell viability after 5 days by CellTiter-Glo assay, EC50 = 3.5 μM. 29170024
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
TY82 Antiproliferative assay 72 hrs Antiproliferative activity against human TY82 cells after 72 hrs by CCK8 assay, IC50 = 0.3043 μM. 29525435
MM1S Antiproliferative assay 72 hrs Antiproliferative activity against human MM1S cells after 72 hrs by CCK8 assay, IC50 = 0.3492 μM. 29525435
TY82 Function assay 0.2 to 1 uM 24 hrs Inhibition of BRD4 in human TY82 cells assessed as reduction in c-Myc protein expression at 0.2 to 1 uM after 24 hrs by Western blot analysis 29525435
TY82 Function assay 0.2 to 1 uM 24 hrs Inhibition of BRD4 in human TY82 cells assessed as reduction in c-Myc mRNA expression at 0.2 to 1 uM after 24 hrs by RT-PCR analysis 29525435
TY82 or NCI-H1299 Function assay 0.2 to 1 uM 24 hrs Inhibition of BRD4 in human TY82 or NCI-H1299 cells assessed as reduction in PD-L1 protein expression at 0.2 to 1 uM after 24 hrs by Western blot analysis 29525435
TY82 or NCI-H1299 Function assay 0.2 to 1 uM 24 hrs Inhibition of BRD4 in human TY82 or NCI-H1299 cells assessed as reduction in PD-L1 mRNA expression at 0.2 to 1 uM after 24 hrs by RT-PCR analysis 29525435
C4-2B Antiproliferative assay 96 hrs Antiproliferative activity against human C4-2B cells after 96 hrs by Cell-Titer glo reagent based luminescence assay 29541371
22Rv1 Antiproliferative assay 96 hrs Antiproliferative activity against human 22Rv1 cells after 96 hrs by Cell-Titer glo reagent based luminescence assay 29541371
LNCAP Antiproliferative assay 96 hrs Antiproliferative activity against human LNCAP cells after 96 hrs by Cell-Titer glo reagent based luminescence assay 29541371
HL60 Cytotoxicity assay Cytotoxicity against human HL60 cells by MTS assay, IC50 = 0.12 μM. 29657099
Raji Function assay Inhibition of BRD4-BD1 in human Raji cells assessed as downregulation of MYC gene expression by PCR method, IC50 = 0.132 μM. 29657099
LNCAP Antiproliferative assay Antiproliferative activity against human LNCAP cells, IC50 = 0.3565 μM. 29758518
MV411 Cytotoxicity assay 72 hrs Cytotoxicity against human MV411 cells after 72 hrs by CellTiter-Glo assay, IC50 = 0.8 μM. 30268702
클릭하여 더 많은 세포주 실험 데이터 보기

화학 정보, 보관 및 안정성

분자량 423.9 화학식

C22H22ClN5O2

보관 (수령일로부터)
CAS 번호 1260907-17-2 SDF 다운로드 원액 보관

동의어 GSK525762, GSK525762A Smiles CCNC(=O)CC1C2=NN=C(N2C3=C(C=C(C=C3)OC)C(=N1)C4=CC=C(C=C4)Cl)C

용해도

In vitro
배치:

DMSO : 84 mg/mL (198.15 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 42 mg/mL

Water : 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

Targets/IC50/Ki
BET proteins
(Cell-free assay)
35 nM
시험관 내(In vitro)
Molibresib (I-BET-762)는 BET (브로모도메인 및 엑스트라 터미널 도메인) 단백질인 BRD2, BRD3, BRD4의 억제제로, BET의 탠덤 브로모도메인에 Kd 50.5–61.3 nM으로 결합하고 FRET 분석에서 IC50 32.5–42.5 nM으로 BET의 탠덤 브로모도메인에 미리 결합된 테트라-아세틸화 H4 펩타이드를 대체합니다. 이 화합물은 BET 단백질의 아세틸-리신 결합 포켓을 차지하고 아세틸화된 히스톤에 대한 결합을 억제하여 염증성 유전자 발현에 필수적인 크로마틴 복합체 형성을 방해합니다. 분화 첫 2일 동안 이 화합물로 치료하면 CD4+ T 세포 사이토카인 생산이 변경되어 여러 항염증성 유전자 산물의 발현이 상향 조절되고 여러 전염증성 사이토카인의 발현이 하향 조절됩니다.
키나아제 분석
형광 공명 에너지 전달 (FRET) 적정
형광 공명 에너지 전달 (FRET) 적정. Molibresib (I-BET-762)는 200 nM BRD2, 100 nM BRD3, 50 nM BRD4에 대해 50 mM HEPES pH 7.5, 50 mM NaCl, 0.5 mM CHAPS, 그리고 200 nM 테트라-아세틸화 히스톤 H4 펩타이드 존재 하에 적정됩니다. 1시간 동안 평형화 후, 브로모도메인 단백질:펩타이드 상호작용은 2 nM 유로퓸 크립테이트 표지 스트렙타비딘과 10 nM XL-665 표지 항-6His 항체를 0.05% (v/v) BSA와 400 mM KF를 포함하는 분석 완충액에 첨가한 후 FRET를 사용하여 감지됩니다. 플레이트는 Envision Plate Reader (여기 320 nm, 방출 615 nm 및 665 nm)를 사용하여 판독됩니다.
생체 내(In vivo)
Molibresib (I-BET-762)는 지질다당류 유도 내독소 쇼크 및 세균 유도 패혈증에 대한 보호를 제공합니다. LPS 주사 후 1.5시간에 단일 용량의 이 화합물을 적용하면 생쥐를 치료하고, 2일 동안 하루 두 번 주사하면 패혈증으로 인한 사망으로부터 보호합니다. 초기 프라이밍 동안에만 제한적으로 치료하면 Th1 분화된 2D2 T 세포가 실험적 자가면역 뇌척수염 (EAE) 마우스 모델에서 신경염증을 유도하는 능력이 억제되었습니다.
참조

적용 분야

방법 바이오마커 이미지 PMID
Growth inhibition assay Cell viability
S7189-viability1
26840085

임상시험 정보

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT03266159 Withdrawn
Solid Tumours
GlaxoSmithKline
November 27 2017 Phase 2
NCT02964507 Terminated
Neoplasms
GlaxoSmithKline
February 2 2017 Phase 1
NCT01943851 Completed
Neoplasms
GlaxoSmithKline
May 14 2014 Phase 2
NCT01587703 Completed
Carcinoma Midline
GlaxoSmithKline
March 28 2012 Phase 1

기술 지원

취급 설명서

Tel: +1-832-582-8158 Ext:3

다른 문의사항이 있으시면 메시지를 남겨주세요.

이름을 입력해주세요.
이메일을 입력해주세요. 유효한 이메일 주소를 입력해주세요.
저희에게 무엇이든 작성해주세요.