PROTAC BRD4 Degrader-1 is a PROTAC protein degrader linked by Cereblon ligand and BRD4 ligand. The IC50 of inhibiting BRD4 BD1 is 41.8 nM. PROTAC BRD4 Degrader-1 can effectively degrade BRD4 protein and inhibit c-Myc expression.

Physicochemical Properties

Molecular Formula	C40H37N9O8
Molecular Weight	771.7773
Exact Mass	771.276
CAS #	2133360-00-4
PubChem CID	141488039
Appearance	White to off-white solid powder
LogP	2.2
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	11
Heavy Atom Count	57
Complexity	1560
Defined Atom Stereocenter Count	0
SMILES	O=C1N(C([H])([H])[H])C2C([H])=C([H])C(C3C(C([H])([H])[H])=NOC=3C([H])([H])[H])=C([H])C=2C([H])(C2C([H])=C([H])C([H])=C([H])C=2[H])N1C([H])([H])C1=C([H])N(C([H])([H])C([H])([H])OC([H])([H])C(N([H])C2=C([H])C([H])=C([H])C3C(N(C(C=32)=O)C2([H])C(N([H])C(C([H])([H])C2([H])[H])=O)=O)=O)=O)N=N1
InChi Key	FXNACIMQXOPNJG-UHFFFAOYSA-N
InChi Code	InChI=1S/C40H37N9O8/c1-22-34(23(2)57-44-22)25-12-13-30-28(18-25)36(24-8-5-4-6-9-24)48(40(55)46(30)3)20-26-19-47(45-43-26)16-17-56-21-33(51)41-29-11-7-10-27-35(29)39(54)49(38(27)53)31-14-15-32(50)42-37(31)52/h4-13,18-19,31,36H,14-17,20-21H2,1-3H3,(H,41,51)(H,42,50,52)
Chemical Name	2-[2-[4-[[6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-methyl-2-oxo-4-phenyl-4H-quinazolin-3-yl]methyl]triazol-1-yl]ethoxy]-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]acetamide
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	PROTAC BRD4 Degrader-1 (Compound 21) (2.5 μM; 24 hours), exhibits modest action against Raji and HL-60 cell lines and strong inhibitory activity against the development of the human monocytic lymphoma cell line THP-1, with an IC50 value of 0.81 μM[1]. Pomalidomide cannot degrade BRD4 at low concentrations, whereas PROTAC BRD4 Degrader-1 (1 μM; 24 hours) can efficiently promote BRD4 protein degradation and inhibit c-Myc [1].
Cell Assay	Cell proliferation assay [1] Cell Types: HL-60, Raji and THP-1 Cell Tested Concentrations: 2.5 μM Incubation Duration: 24 hrs (hours) Experimental Results: Inhibition of HL-60, Raji and THP-1 cell growth. Western Blot Analysis[1] Cell Types: THP-1 Cell Tested Concentrations: 1 μM Incubation Duration: 3 hrs (hours) Experimental Results: BRD4 protein degrades and inhibits c-Myc expression.
References	[1]. Discovery of a new class of PROTAC BRD4 degraders based on a dihydroquinazolinone derivative and lenalidomide/pomalidomide.Bioorg Med Chem. 2020 Jan 1;28(1):115228.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~129.57 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5 mg/mL (6.48 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 50.0 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	1.2957 mL	6.4785 mL	12.9571 mL
	5 mM	0.2591 mL	1.2957 mL	2.5914 mL
	10 mM	0.1296 mL	0.6479 mL	1.2957 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.