EBI-2511 is a novel and orally available benzofuran derived EZH2 inhibitors that was discovered through a scaffold hopping approach based on the clinical compound of EPZ-6438. It has the potential for treatment of Non-Hodgkin’s Lymphoma. Further rational structure-activity relationship exploration and optimization led to the discovery of more potent EZH2 inhibitors with oral bioavailability in mice and rats. EBI-2511 demonstrated excellent in vivo efficacy in Pfeiffer tumor Xenograft models in mouse and is under preclinical development for the treatment of cancers associated with EZH2 mutations.

Physicochemical Properties

Molecular Formula	C34H48N4O4
Molecular Weight	576.769329071045
Exact Mass	576.367
CAS #	2098546-05-3
Related CAS #	2098546-05-3
PubChem CID	133081962
Appearance	White to off-white solid powder
LogP	5.3
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	9
Heavy Atom Count	42
Complexity	1030
Defined Atom Stereocenter Count	0
SMILES	O1C2=CC(N(CC)C3CCOCC3)=C(CC)C(C(NCC3=C(C)C=C(C)NC3=O)=O)=C2C=C1C1CCN(C(C)C)CC1
InChi Key	NYWVSLBALKNFJR-UHFFFAOYSA-N
InChi Code	InChI=1S/C34H48N4O4/c1-7-26-29(38(8-2)25-11-15-41-16-12-25)19-31-27(18-30(42-31)24-9-13-37(14-10-24)21(3)4)32(26)34(40)35-20-28-22(5)17-23(6)36-33(28)39/h17-19,21,24-25H,7-16,20H2,1-6H3,(H,35,40)(H,36,39)
Chemical Name	N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-ethyl-6-(ethyl-(tetrahydro-2H-pyran-4-yl)amino)-2-(1-isopropylpiperidin-4-yl)benzofuran-4-carboxamide
Synonyms	EBI-2511; EBI 2511; EBI2511
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	EBI-2511 (Compound 34) dramatically decreases cellular H3K27me3 levels in a dose-dependent manner with an approximate IC50 of 8 nM, which is 3-fold more effective than EPZ-6438. In addition to Pfeffier cell line, EBI-2511 was found active with IC50 value of 55 nM against WSU-DLCL2[1].
ln Vivo	EBI-2511 has a dose-dependent suppression of tumor growth, leading to a reduction in tumor size of 28% (10 mg/kg), 83% (30 mg/kg), and 97% (100 mg/kg). EBI-2511 outperforms EPZ-6438 in terms of anti-tumor activity at the same dosage level (P<0.01). Notably, there are no appreciable variations in the body weights of any treatment groups[1].
Animal Protocol	10, 30, 100 mg/kg; Oral Pfeiffer tumor Xenograft models in mouse
References	[1]. Discovery of EBI-2511: A Highly Potent and Orally Active EZH2 Inhibitor for the Treatment of Non-Hodgkin's Lymphoma. ACS Med Chem Lett. 2018 Jan 29;9(2):98-102.

Solubility Data

Solubility (In Vitro)

DMSO:10 mM Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 0.5 mg/mL (0.87 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.5 mg/mL (0.87 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 0.5 mg/mL (0.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.7338 mL	8.6690 mL	17.3379 mL
	5 mM	0.3468 mL	1.7338 mL	3.4676 mL
	10 mM	0.1734 mL	0.8669 mL	1.7338 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.