연구용
제품 번호S7189
| 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 | ||||||
| 분자량 | 423.9 | 화학식 | C22H22ClN5O2 |
보관 (수령일로부터) | |
|---|---|---|---|---|---|
| CAS 번호 | 1260907-17-2 | SDF 다운로드 | 원액 보관 |
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| 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 | ||
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In vitro |
DMSO
: 84 mg/mL
(198.15 mM)
Ethanol : 42 mg/mL Water : Insoluble |
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In vivo |
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1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)
2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)
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.
| 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.
|
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| 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.
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참조 |
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| 방법 | 바이오마커 | 이미지 | PMID |
|---|---|---|---|
| Growth inhibition assay | Cell viability |
|
26840085 |
(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 |