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I-BET151 (GSK1210151A) BET Inhibitor

Name: I-BET151 (GSK1210151A)
Brand: Selleck Chemicals
SKU: S2780
Rating: 5 (61 reviews)

Kat.-Nr.S2780

I-BET151 (GSK1210151A) ist ein neuartiger selektiver BET-Inhibitor, der auf BRD2, BRD3 und BRD4 mit jeweiligen IC50-Werten von 0,5 μM, 0,25 μM und 0,79 μM in zellfreien Assays abzielt.

I-BET151 (GSK1210151A) BET Inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 415.44

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Qualitätskontrolle

Charge: Reinheit: 99.99%

99.99

Verwandte Ziele	HDAC JAK Histone Methyltransferase PKC PARP HIF PRMT EZH2 AMPK Histone Acetyltransferase
Weitere BET Inhibitoren	Pelabresib (CPI-0610) ZEN-3694 (BET-IN-19) Molibresib (I-BET-762) Mivebresib (ABBV-075) INCB054329 Birabresib (OTX015) Apabetalone (RVX-208) AZD5153 6-hydroxy-2-naphthoic acid CPI-203 I-BRD9

Zellkultur, Behandlung & Arbeitskonzentration

Zelllinien	Assay-Typ	Konzentration	Inkubationszeit	Formulierung	Aktivitätsbeschreibung	PMID
MV4;11	cytotoxicity assay	~100 μM		DMSO	IC50=26 nM	21964340
RS4;11	cytotoxicity assay	~100 μM		DMSO	IC50=192 nM	21964340
MOLM13	cytotoxicity assay	~100 μM		DMSO	IC50=120 nM	21964340
NOMO1	cytotoxicity assay	~100 μM		DMSO	IC50=15 nM	21964340
HEL	cytotoxicity assay	~100 μM		DMSO	IC50=1 μM	21964340
K562	cytotoxicity assay	~100 μM		DMSO	IC50>100 μM	21964340
MEG01	cytotoxicity assay	~100 μM		DMSO	IC50=25 μM	21964340
HL60	cytotoxicity assay	~100 μM		DMSO	IC50=890 nM	21964340
MV4;11	Apoptosis assay	~100 μM		DMSO	induces apoptosis	21964340
MOLM13	Apoptosis assay	~100 μM		DMSO	induces apoptosis	21964340
MV4;11	Function assay			DMSO	decreases the recruitment of BRD3/4 and impaired recruitment of CDK9 and PAF1 to the transcriptional start site	21964340
PBMC	Function assay			DMSO	inhibits IL-6 with pIC50 of 6.7	22437115
A2	Function assay	~10 μM		DMSO	reactivates latent HIV-1	23255218
A72	Function assay	~10 μM		DMSO	reactivates latent HIV-1	23255218
BC1	Growth inhibitory assay	~1 μM		DMSO	IC50=220 nM	23792448
BC3	Growth inhibitory assay	~1 μM		DMSO	IC50=460 nM	23792448
BCBL1	Growth inhibitory assay	~1 μM		DMSO	IC50=330 nM	23792448
BJAB	Growth inhibitory assay	~1 μM		DMSO	IC50=970 nM	23792448
Namalwa	Growth inhibitory assay	~1 μM		DMSO	IC50=970 nM	23792448
Jurkat	Growth inhibitory assay	~1 μM		DMSO	IC50=1220 nM	23792448
MM1S	Growth inhibitory assay	~1 μM		DMSO	IC50=760 nM	23792448
U266	Growth inhibitory assay	~1 μM		DMSO	IC50=950 nM	23792448
UM-PEL-1	Growth inhibitory assay	~1 μM		DMSO	IC50=210 nM	23792448
UM-PEL-3	Growth inhibitory assay	~1 μM		DMSO	IC50=180 nM	23792448
BC1	Function assay	500 nM		DMSO	induces cell-cycle arrest	23792448
BC3	Function assay	500 nM		DMSO	induces cell-cycle arrest	23792448
BC1	Function assay	800 nM		DMSO	reduces c-Myc protein levels	23792448
BC3	Function assay	800 nM		DMSO	reduces c-Myc protein levels	23792448
H929	Function assay	~1 μM		DMSO	induces cell cycle arrest	24335499
KMS12PE	Function assay	~1 μM		DMSO	induces cell cycle arrest	24335499
KMS12BM	Function assay	~1 μM		DMSO	induces cell cycle arrest	24335499
KMS18	Function assay	~1 μM		DMSO	induces cell cycle arrest	24335499
KMS11	Function assay	~1 μM		DMSO	induces cell cycle arrest	24335499
RPMI8226	Function assay	~1 μM		DMSO	induces cell cycle arrest	24335499
H929	Apoptosis assay	~1 μM		DMSO	induces cell apoptosis	24335499
KMS12PE	Apoptosis assay	~1 μM		DMSO	induces cell apoptosis	24335499
KMS12BM	Apoptosis assay	~1 μM		DMSO	induces cell apoptosis	24335499
KMS18	Apoptosis assay	~1 μM		DMSO	induces cell apoptosis	24335499
KMS11	Apoptosis assay	~1 μM		DMSO	induces cell apoptosis	24335499
RPMI8226	Apoptosis assay	~1 μM		DMSO	induces cell apoptosis	24335499
U87MG	Function assay	~10 μM		DMSO	reduces U87MG cellular ATP with IC50 of 1.05 μM	24496381
A172	Function assay	~10 μM		DMSO	reduces cellular ATP with IC50 of 1.28 μM	24496381
SW1783	Function assay	~10 μM		DMSO	reduces cellular ATP with IC50 of 2.68 μM	24496381
U87MG	Function assay	~10 μM		DMSO	increases proportion of cells in the G1/S transition	24496381
RAW267.4	Function assay	1 μM		DMSO	reduces IL-6 production induced by LPS	24859008
RAW267.4	Function assay	1 μM		DMSO	reduces the association between BRD4 and acetylated p65	24859008
Me007	Growth inhibitory assay	~100 μM		DMSO	inhibits the growth	24906137
SK-Mel-28	Growth inhibitory assay	~100 μM		DMSO	inhibits the growth	24906137
Mel-RMU	Growth inhibitory assay	~100 μM		DMSO	inhibits the growth	24906137
Mel-JD	Growth inhibitory assay	~100 μM		DMSO	inhibits the growth	24906137
Mel-RM	Growth inhibitory assay	~100 μM		DMSO	inhibits the growth	24906137
Me007	Apoptosis assay	~100 μM		DMSO	induces apoptosis	24906137
SK-Mel-28	Apoptosis assay	~100 μM		DMSO	induces apoptosis	24906137
Mel-RMU	Apoptosis assay	~100 μM		DMSO	induces apoptosis	24906137
Mel-JD	Apoptosis assay	~100 μM		DMSO	induces apoptosis	24906137
Mel-RM	Apoptosis assay	~100 μM		DMSO	induces apoptosis	24906137
Me007	Function assay	10 μM		DMSO	induces cell cycle arrest by upregulation of p21	24906137
SK-Mel-28	Function assay	10 μM		DMSO	induces cell cycle arrest by upregulation of p21	24906137
Mel-RMU	Function assay	10 μM		DMSO	induces cell cycle arrest by upregulation of p21	24906137
Mel-JD	Function assay	10 μM		DMSO	induces cell cycle arrest by upregulation of p21	24906137
Mel-RM	Function assay	10 μM		DMSO	induces cell cycle arrest by upregulation of p21	24906137
Me007	Function assay	10 μM		DMSO	upregulates proapoptotic and cell cycle arrest genes	24906137
SK-Mel-28	Function assay	10 μM		DMSO	upregulates proapoptotic and cell cycle arrest genes	24906137
Mel-RMU	Function assay	10 μM		DMSO	upregulates proapoptotic and cell cycle arrest genes	24906137
Mel-JD	Function assay	10 μM		DMSO	upregulates proapoptotic and cell cycle arrest genes	24906137
Mel-RM	Function assay	10 μM		DMSO	upregulates proapoptotic and cell cycle arrest genes	24906137
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 = 0.09 μM.	22386529
Raji	Function assay		4 hrs		Inhibition of BRD4 in human Raji cells assessed as reduction of MYC expression after 4 hrs, IC50 = 0.13 μM.	24900758
MV4-11	Growth inhibition assay		72 hrs		Growth inhibition of human MV4-11 cells after 72 hrs by SRB assay, IC50 = 0.119 μM.	25559428
MM1S	Growth inhibition assay		72 hrs		Growth inhibition of human MM1S cells after 72 hrs by SRB assay, IC50 = 0.299 μM.	25559428
HT-29	Growth inhibition assay		72 hrs		Growth inhibition of human HT-29 cells after 72 hrs by SRB assay, IC50 = 0.945 μM.	25559428
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 = 0.0317 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 = 0.162 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 = 0.226 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 = 0.228 μM.	26080064
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 = 0.0317 μM.	28463487
MV4-11	Growth inhibition assay		4 days		Growth inhibition of human MV4-11 cells after 4 days by WST-8 assay, IC50 = 0.162 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 = 0.226 μM.	28463487
MOLM13	Growth inhibition assay		4 days		Growth inhibition of human MOLM13 cells after 4 days by WST-8 assay, IC50 = 0.228 μM.	28463487
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 = 0.0298 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 = 0.0405 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 = 0.0528 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 = 0.0548 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 = 0.0703 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 = 0.215 μM.	26080064
Rosetta2 DE3	Function assay				Binding affinity to biotinylated CREBBP (1043 to 1159 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 3.084 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 = 0.0072 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 = 0.009 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 = 0.009 μM.	26080064
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 = 0.0223 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 = 0.0496 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 = 0.0748 μM.	26080064
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 = 0.009 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, Ki = 0.0748 μM.	28463487
THP1	Antiinflammatory assay				Antiinflammatory activity in human THP1 cells	22386529
HT-29	Function assay	0.3125 uM to 5 uM	24 hrs		Inhibition of BRD4 in human HT-29 cells assessed as reduction in c-Myc protein expression at 0.3125 uM to 5 uM uM after 24 hrs by Western blotting method	25559428
MV4-11	Function assay				Inhibition of BRD4 in human MV4-11 cells assessed as downregulation of BCL2 RNA expression by RNA-seq analysis	29259751
MV4-11	Function assay				Inhibition of BRD4 in human MV4-11 cells assessed as downregulation of cMYC RNA expression by RNA-seq analysis	29259751
U-2 OS	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	29435139
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
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
SK-N-SH	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
BT-12	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 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
fibroblast cells	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells	29435139
Rh41	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
Rh30	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 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
Rh18	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
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Chemische Informationen, Lagerung & Stabilität

Molekulargewicht	415.44	Formel	C₂₃H₂₁N₅O₃	Lagerung (Ab dem Eingangsdatum)	3 Jahre-20°CPulver
CAS-Nr.	1300031-49-5	SDF herunterladen		Lagerung von Stammlösungen	1 Jahr-80°Cin Lösungsmittel 1 Monat-20°Cin Lösungsmittel
Synonyme	N/A			Smiles	CC1=C(C(=NO1)C)C2=C(C=C3C(=C2)N=CC4=C3N(C(=O)N4)C(C)C5=CC=CC=N5)OC

Löslichkeit

In vitro
Charge:

DMSO : 83 mg/mL (199.78 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 83 mg/mL

Water : Insoluble

DMSO : 83 mg/mL (199.78 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 27 mg/mL

Water : Insoluble

Molaritätsrechner

Masse	Konzentration	Volumen	Molekulargewicht
=	×	×

Verdünnungsrechner Molekulargewichtsrechner

In vivo Charge:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil Von Selleck Labs validiert. Sollten Sie Anpassungen an dieser Formulierung benötigen, kontaktieren Sie unser Verkaufsteam für kundenspezifische Tests.	4.500mg/ml (10.83mM)	Taking the 1 mL working solution as an example, add 50 μL of 90 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In-vivo-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie die untenstehenden Informationen ein (Empfohlen: Ein zusätzliches Tier zur Berücksichtigung von Verlusten während des Experiments)

Dosierung: mg/kg Durchschnittsgewicht der Tiere: g Dosiervolumen pro Tier:μL Anzahl der Tiere:

Schritt 2: Geben Sie die In-vivo-Formulierung ein (Dies ist nur der Rechner, keine Formulierung. Bitte kontaktieren Sie uns zuerst, wenn es im Abschnitt "Löslichkeit" keine In-vivo-Formulierung gibt.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

Methode zur Herstellung der DMSO-Stammlösung: mg Wirkstoff vorgelöst in μL DMSO ( Konzentration der Stammlösung mg/mL, Bitte kontaktieren Sie uns zuerst, wenn die Konzentration die DMSO-Löslichkeit der Wirkstoffcharge überschreitet. )

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügenμL PEG300, mischen und klären, dann hinzufügenμL Tween 80, mischen und klären, dann hinzufügen μL ddH₂O, mischen und klären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügen μL Maisöl, mischen und klären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, das/die Lösungsmittel der Reihe nach hinzuzufügen. Sie müssen sicherstellen, dass die bei der vorherigen Zugabe erhaltene Lösung eine klare Lösung ist, bevor Sie mit der Zugabe des nächsten Lösungsmittels fortfahren. Physikalische Methoden wie Vortex, Ultraschall oder ein heißes Wasserbad können zur Unterstützung des Lösens verwendet werden.

Wirkmechanismus

Merkmale	Optimized to retain excellent BET target potency and selectivity while enhancing the in vivo pharmacokinetics and terminal half-life to enable prolonged in vivo studies.
Targets/IC₅₀/Ki	BRD3 (Cell-free assay) 0.25 μM BRD2 (Cell-free assay) 0.5 μM BRD4 (Cell-free assay) 0.79 μM
In vitro	I-BET151 (GSK1210151A) zeigt eine potente Selektivität über eine Vielzahl unterschiedlicher Proteintypen wie COX-2, P450, Aurora B, GSK3β, PI3K-γ, GPCR, Ionenkanäle und Transporter. Ähnlich wie I-BET762 (GSK525762A) zeigt es eine potente Bindungsaffinität zu BRD2, BRD3 und BRD4 mit einem K_D von 0,02-0,1 μM und hemmt signifikant die Lipopolysaccharid-stimulierte IL-6-Zytokinproduktion in humanen peripheren mononukleären Zellen (PBMC) und Vollblut (WB) sowie Ratten-WB mit einem IC50 von 0,16 μM, 1,26 μM bzw. 1,26 μM. Diese Verbindung (0,5 oder 5 μM) hemmt die Bindung von BETs (BRD2, BRD3, BRD4 und BRD9), aber nicht die Bindung von 23 anderen Bromodomänenproteinen im HL60-Kernextrakt an acetylierte Histonpeptide. Es hat eine potente Wirksamkeit gegen Zelllinien, die verschiedene MLL-Fusionen wie MV4;11, RS4;11, MOLM13 und NOMO1-Zellen mit einem IC50 von 15-192 nM aufweisen. Konsistenterweise ablatiert es vollständig das Kolonie-bildende Potenzial von MLL-Fusions-getriebenen Leukämien (MOLM13), aber nicht von Leukämien, die durch Tyrosinkinase-Aktivierung (K562) angetrieben werden. I-BET151 zeigt auch eine potente Wirksamkeit in sowohl Flüssigkeitskultur- als auch klonogenen Assays unter Verwendung primärer muriner Vorläuferzellen, die entweder mit MLL-ENL oder MLL-AF9 transformiert wurden. Die Behandlung mit dieser Verbindung induziert signifikant Apoptose und einen prominenten G0/G1-Arrest in MLL-Fusionszelllinien, die durch unterschiedliche MLL-Fusionen angetrieben werden (MOLM13 und MV4;11, die MLL-AF9 bzw. MLL-AF4 enthalten), aber nicht in K562-Zellen, wahrscheinlich aufgrund der Hemmung der Transkription von BCL2, C-MYC und CDK6 durch Blockierung der Rekrutierung von BRD3/4-, PAFc- und SEC-Komponenten an die Transkriptionsstartstelle (TSS).
Kinase-Assay	Fluoreszenzanisotropie (FP) Ligandenverdrängungsassay
Kinase-Assay	Alle Komponenten werden in einem Puffer der Zusammensetzung 50 mM HEPES pH 7,4, 150 mM NaCl und 0,5 mM CHAPS gelöst, mit Endkonzentrationen von BRD 2/3/4 75 nM, fluoreszierendem Liganden 5 nM. 10 μL dieser Reaktionsmischung werden mit einem Mikro-Multidrop in Vertiefungen gegeben, die 100 nL verschiedener Konzentrationen von I-BET151 (GSK1210151A) oder DMSO-Träger (1 % final) in einer Greiner 384-Well Black Low Volume Mikrotiterplatte enthalten und 60 Minuten bei Raumtemperatur im Dunkeln äquilibriert werden. Die Fluoreszenzanisotropie wird im Envision (lex = 485 nm, lEM = 530 nm; Dichroit = 505 nM) abgelesen.
In vivo	I-BET151 (GSK1210151A) hemmt, wenn es in einer Dosis von 30 mg/kg/Tag verabreicht wird, signifikant das Tumorwachstum von muriner MLL-AF9- und humaner MLL-AF4-Leukämie bei Mäusen und bietet einen deutlichen Überlebensvorteil.
Literatur	[1] https://pubmed.ncbi.nlm.nih.gov/21964340/

Anwendungen

Methoden	Biomarker	Bilder	PMID
Western blot	α-SMA / Fibronectin / Collagen-1 FoxM1 / AURKB / Survivin / cyclin B / PLK1 HP1α / HP1β / HP1γ		27732564

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