Home Epigenetics Epigenetic Reader Domain inhibitor I-BET151 (GSK1210151A) For research use only.

I-BET151 (GSK1210151A)

I-BET151 (GSK1210151A) is a novel selective BET inhibitor for BRD2, BRD3 and BRD4 with IC50 of 0.5 μM, 0.25 μM, and 0.79 μM in cell-free assays, respectively.

I-BET151 (GSK1210151A) Chemical Structure

I-BET151 (GSK1210151A) Chemical Structure

CAS No. 1300031-49-5

Purity & Quality Control

I-BET151 (GSK1210151A) Related Products

Signaling Pathway

Epigenetic Reader Domain Signaling Pathways

Epigenetic Reader Domain Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description 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
Click to View More Cell Line Experimental Data

Biological Activity

Description I-BET151 (GSK1210151A) is a novel selective BET inhibitor for BRD2, BRD3 and BRD4 with IC50 of 0.5 μM, 0.25 μM, and 0.79 μM in cell-free assays, respectively.
Features 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
BRD3 [1]
(Cell-free assay)		 BRD2 [1]
(Cell-free assay)		 BRD4 [1]
(Cell-free assay)
0.25 μM 0.5 μM 0.79 μM
In vitro
In vitro I-BET151 exhibits potent selectivity over an extensive range of diverse protein types such as COX-2, P450, Aurora B, GSK3β, PI3K-γ, GPCR, ion channels, and transporters. Similar to I-BET762 (GSK525762A), I-BET151 displays potent binding affinity to BRD2, BRD3 and BRD4 with KD of 0.02-0.1 μM, and significantly inhibits lipopolysaccharide-stimulated IL-6 cytokine production in human peripheral blood mononuclear cells (PBMC) and whole blood (WB) as well as rat WB with IC50 of 0.16 μM, 1.26 μM, and 1.26 μM, respectively. I-BET151 (0.5 or 5 μM) inhibits the binding of BETs (BRD2, BRD3, BRD4, and BRD9) but not the binding of 23 other bromodomain proteins in HL60 nuclear extract to acetylated histone peptides. I-BET151 has potent efficacy against cell lines harboring different MLL-fusions such as MV4;11, RS4;11, MOLM13, and NOMO1 cells with IC50 of 15-192 nM. Consistently, I-BET151 completely ablates the colony-forming potential of MLL-fusion-driven leukaemias (MOLM13) but not leukaemias driven by tyrosine kinase activation (K562). I-BET151 also displays potent efficacy in both liquid culture and clonogenic assays using primary murine progenitors transformed with either MLL-ENL or MLL-AF9. I-BET151 treatment significantly induces apoptosis and prominent G0/G1 arrest in MLL-fusion cell lines driven by distinct MLL fusions (MOLM13 and MV4;11 containing MLL-AF9 and MLL-AF4, respectively) but not the K562 cells, probably due to the inhibition of transcription of BCL2, C-MYC and CDK6 by blocking the recruitment of BRD3/4, PAFc and SEC components into transcriptional start site (TSS). [1]
Kinase Assay Fluorescence anisotropy (FP) ligand displacement assay
All components are dissolved in buffer of composition 50 mM HEPES pH 7.4, 150 mM NaCl and 0.5 mM CHAPS with final concentrations of BRD 2/3/4 75 nM, fluorescent ligand 5 nM. 10 μL of this reaction mixture is added using a micro multidrop to wells containing 100 nL of various concentrations of I-BET151 or DMSO vehicle (1% final) in Greiner 384 well Black low volume microtitre plate and equilibrated in the dark for 60 minutes at room temperature. Fluorescence anisotropy is read in Envision (lex = 485 nm, lEM = 530 nm; Dichroic = 505 nM).
Cell Research Cell lines MV4;11, MOLM13, NOMO1, RS4;11, HEL, HL60 and K562
Concentrations Dissolved in DMSO, final concentrations ~100 μM
Incubation Time 24, or 72 hours
Method

Cells are exposed to various concentrations of I-BET151 for 24 or 72 hours in 384-well or 96-well plates. For cell growth inhibition assays, plates are added with CellTiter-Glo reagent using a volume equivalent to the cell culture volume in the wells, shaken for approximately 2 minutes and chemiluminescent signal is read on the Analyst GT or EnVision Plate Reader. For cell proliferation assays, CellTiter-Aqueous One is added to each well and plates are incubated for 4 hours at 37 °C. Absorbance is read at 490 nm on a SpectraMax Gemini reader
Experimental Result Images Methods Biomarkers Images PMID
Western blot α-SMA / Fibronectin / Collagen-1 FoxM1 / AURKB / Survivin / cyclin B / PLK1 HP1α / HP1β / HP1γ 27732564
In Vivo
In vivo Administration of I-BET151 at 30 mg/kg/day significantly inhibits tumor growth of murine MLL-AF9 and human MLL-AF4 leukaemia in mice, and provides marked survival benefit. [1]
Animal Research Animal Models NOD-SCID mice injected intravenously with MV4;11 cells, and C57BL/6 mice injected intravenously with MLL-AF9 cells
Dosages ~30 mg/kg/day
Administration Intraperitoneal injection

Chemical Information & Solubility

Molecular Weight 415.44 Formula

C23H21N5O3
CAS No. 1300031-49-5 SDF Download I-BET151 (GSK1210151A) SDF
Smiles CC1=C(C(=NO1)C)C2=C(C=C3C(=C2)N=CC4=C3N(C(=O)N4)C(C)C5=CC=CC=N5)OC
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 83 mg/mL ( (199.78 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 83 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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