solo per uso di ricerca
N. Cat.S7189
| Linee cellulari | Tipo di saggio | Concentrazione | Tempo di incubazione | Formulazione | Descrizione dell'attività | 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 | ||
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| Peso molecolare | 423.9 | Formula | C22H22ClN5O2 |
Conservazione (Dalla data di ricezione) | |
|---|---|---|---|---|---|
| N. CAS | 1260907-17-2 | Scarica SDF | Conservazione delle soluzioni stock |
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| Sinonimi | 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 |
|
In vivo |
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Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante l'esperimento)
Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non c'è una formulazione in vivo nella sezione Solubilità.)
Risultati del calcolo:
Concentrazione di lavoro: mg/ml;
Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )
Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH2O, mescolare e chiarire.
Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.
Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nell'aggiunta precedente, sia una soluzione limpida prima di procedere all'aggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno d'acqua calda possono essere utilizzati per facilitare la dissoluzione.
| Targets/IC50/Ki |
BET proteins
(Cell-free assay) 35 nM
|
|---|---|
| In vitro |
Molibresib (I-BET-762) è un inibitore per le proteine BET (bromodomain e dominio extra terminale), BRD2, BRD3 e BRD4, che si lega ai bromodomini tandem di BET con Kd di 50,5–61,3 nM e sposta un peptide H4 tetra-acetilato pre-legato ai bromodomini tandem di BET con IC50 di 32,5–42,5 nM nell'analisi FRET. Questo composto occupa la tasca di legame dell'acetil-lisina delle proteine BET e ne inibisce il legame agli istoni acetilati, interrompendo così la formazione di complessi di cromatina essenziali per l'espressione dei geni infiammatori. Il trattamento con esso durante i primi 2 giorni di differenziazione altera la produzione di citochine delle cellule T CD4+, sovraregolando l'espressione di diversi prodotti genici antinfiammatori e sottoregolando l'espressione di diverse citochine proinfiammatorie.
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| Saggio chinasico |
Titolazioni per trasferimento di energia di risonanza di fluorescenza (FRET)
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Titolazioni per trasferimento di energia di risonanza di fluorescenza (FRET). Molibresib (I-BET-762) è titolato contro BRD2 (200 nM), BRD3 (100 nM) e BRD4 (50 nM) in 50 mM HEPES pH7.5, 50 mM NaCl, 0.5 mM CHAPS in presenza di peptide istone H4 tetra-acetilato (200 nM). Dopo equilibrazione per 1 ora, l'interazione proteina bromodominio:peptide viene rilevata usando FRET in seguito all'aggiunta di 2 nM di streptavidina marcata con criptato di Europio e 10 nM di anticorpo anti-6His marcato con XL-665 in tampone di saggio contenente 0,05% (v/v) BSA e 400 mM KF. Le piastre vengono lette usando un lettore di piastre Envision (eccitazione 320 nm, emissione 615 nm e 665 nm).
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| In vivo |
Molibresib (I-BET-762) conferisce protezione contro lo shock endotossico indotto da lipopolisaccaridi e la sepsi indotta da batteri. Una singola dose di questo composto applicata 1,5 ore dopo l'iniezione di LPS cura i topi, e iniezioni due volte al giorno per 2 giorni li proteggono dalla morte causata da sepsi. Il trattamento limitato con esso esclusivamente durante il priming precoce ha inibito la capacità delle cellule T 2D2 differenziate Th1 di indurre neuroinfiammazione in un modello murino di encefalomielite autoimmune sperimentale (EAE).
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Riferimenti |
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| Metodi | Biomarcatori | Immagini | PMID |
|---|---|---|---|
| Growth inhibition assay | Cell viability |
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26840085 |
(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)
| Numero NCT | Reclutamento | Condizioni | Sponsor/Collaboratori | Data di inizio | Fasi |
|---|---|---|---|---|---|
| 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 |