PROTAC BET Degrader-1 is a PROTAC protein degrader linked by Cereblon ligand and BET ligand, which can reduce the protein levels of BRD2, BRD3 and BRD4 at low concentrations.

Physicochemical Properties

Molecular Formula	C44H45N11O9
Molecular Weight	871.89640879631
Exact Mass	871.34
CAS #	2093386-22-0
PubChem CID	134691733
Appearance	Light yellow to yellow solid powder
LogP	3.8
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	14
Rotatable Bond Count	16
Heavy Atom Count	64
Complexity	1770
Defined Atom Stereocenter Count	0
SMILES	N1C2=C(C=C(OC)C(C3=C(C)ON=C3C)=C2)C2=C(NC3N(CC)N=C(C4CC4)C=3)N=C(C(NCCCCNC(COC3=CC=CC4=C3C(=O)N(C3CCC(=O)NC3=O)C4=O)=O)=O)N=C12
InChi Key	TXLUZGFDBDQACL-UHFFFAOYSA-N
InChi Code	InChI=1S/C44H45N11O9/c1-5-54-32(19-27(52-54)23-11-12-23)48-39-37-25-18-31(62-4)26(35-21(2)53-64-22(35)3)17-28(25)47-38(37)50-40(51-39)42(59)46-16-7-6-15-45-34(57)20-63-30-10-8-9-24-36(30)44(61)55(43(24)60)29-13-14-33(56)49-41(29)58/h8-10,17-19,23,29H,5-7,11-16,20H2,1-4H3,(H,45,57)(H,46,59)(H,49,56,58)(H2,47,48,50,51)
Chemical Name	4-[(5-cyclopropyl-2-ethylpyrazol-3-yl)amino]-7-(3,5-dimethyl-1,2-oxazol-4-yl)-N-[4-[[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetyl]amino]butyl]-6-methoxy-9H-pyrimido[4,5-b]indole-2-carboxamide
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	RS4;11 cells' BRD2, BRD3, and BRD4 protein levels are reduced by PROTAC BET Degrader-1 (Compound 9), a strong PROTAC-based BET degrader that also passes the IC50 of MOLM-13 cells, which are 4.3 nM and 45.5 nM[1].
References	[1]. Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression. J Med Chem. 2018 Jan 25;61(2):462-481.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 50 mg/mL (~57.35 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.67 mg/mL (1.92 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 16.7 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: ≥ 1.67 mg/mL (1.92 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 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	1.1469 mL	5.7346 mL	11.4692 mL
	5 mM	0.2294 mL	1.1469 mL	2.2938 mL
	10 mM	0.1147 mL	0.5735 mL	1.1469 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.