PROTAC BRD4 Degrader-5-CO-PEG3-N3 (Compound 2) A PROTAC-linker conjugate for PAC, containing the BRD4 degrader GNE-987 and 3 PEG linkers. PROTAC BRD4 Degrader-5-CO-PEG3-N3 is a reagent for click chemistry. It has an Azide (N3) moiety and could undergo CuAAc (copper-catalyzed azide-alkyne cycloaddition reaction) with compounds bearing an Alkyne group. SPAAC (Strain-promoted alkyne-azide cycloaddition) may also happen with compounds bearing a BCN or DBCO group.

Physicochemical Properties

Molecular Formula	C58H75CLN12O12S2
Molecular Weight	1231.87230992317
Exact Mass	1230.475
CAS #	2704602-92-4
PubChem CID	146673077
Appearance	White to off-white solid powder
LogP	6.4
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	20
Rotatable Bond Count	34
Heavy Atom Count	85
Complexity	2220
Defined Atom Stereocenter Count	5
SMILES	CC1=C(SC2=C1C(=N[C@H](C3=NN=C(N32)C)CC(=O)NCCOCCOCCOCC(=O)N[C@H](C(=O)N4C[C@@H](C[C@H]4C(=O)N[C@@H](C)C5=CC=C(C=C5)C6=C(N=CS6)C)OC(=O)COCCOCCOCCN=[N+]=[N-])C(C)(C)C)C7=CC=C(C=C7)Cl)C
InChi Key	WMOYJXQCSDGERS-WVLZNWKQSA-N
InChi Code	InChI=1S/C58H75ClN12O12S2/c1-35-38(4)85-57-50(35)51(41-13-15-43(59)16-14-41)65-45(54-68-67-39(5)71(54)57)30-47(72)61-17-19-77-21-23-79-25-27-81-32-48(73)66-53(58(6,7)8)56(76)70-31-44(83-49(74)33-82-28-26-80-24-22-78-20-18-63-69-60)29-46(70)55(75)64-36(2)40-9-11-42(12-10-40)52-37(3)62-34-84-52/h9-16,34,36,44-46,53H,17-33H2,1-8H3,(H,61,72)(H,64,75)(H,66,73)/t36-,44+,45-,46-,53+/m0/s1
Chemical Name	[(3R,5S)-1-[(2S)-2-[[2-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-5-[[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]carbamoyl]pyrrolidin-3-yl] 2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]acetate
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

References

[1]. Antibody-PROTAC Conjugates Enable HER2-Dependent Targeted Protein Degradation of BRD4. ACS Chem Biol. 2020 Jun 19;15(6):1306-1312.

Solubility Data

Solubility (In Vitro)

DMSO : 20 mg/mL (16.24 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 75 mg/mL (60.88 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 750.0 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 2: 7.5 mg/mL (6.09 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 75.0 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 3: ≥ 2 mg/mL (1.62 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 20.0 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	0.8118 mL	4.0589 mL	8.1177 mL
	5 mM	0.1624 mL	0.8118 mL	1.6235 mL
	10 mM	0.0812 mL	0.4059 mL	0.8118 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.