PROTAC Bcl2 degrader-1 (Compound C5) is a PROTAC based on Cereblon ligand, which is effective and specific by introducing pomalidomide, the ligand of E3 ligase cereblon, into the Mcl-1/Bcl-2 dual (bifunctional) inhibitor Nap-1. Sexually induces the degradation of Bcl-2 (IC50, 4.94 μM; DC50, 3.0 μM) and Mcl-1 (IC50, 11.81 μM).

Physicochemical Properties

Molecular Formula	C45H45BRN6O10S
Molecular Weight	941.842009305954
Exact Mass	940.21
CAS #	2378801-85-3
PubChem CID	139035047
Appearance	Light yellow to yellow solid powder
LogP	4.3
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	12
Rotatable Bond Count	21
Heavy Atom Count	63
Complexity	1700
Defined Atom Stereocenter Count	0
SMILES	BrC1C=CC(=CC=1)SC1C=CC2C(N(C(C3=CC=CC=1C=23)=O)CCNC(CCCCC(NCCOCCOCCNC1=CC=CC2C(N(C(C=21)=O)C1C(NC(CC1)=O)=O)=O)=O)=O)=O
InChi Key	IUSLKFLLLNNOGR-UHFFFAOYSA-N
InChi Code	InChI=1S/C45H45BrN6O10S/c46-27-11-13-28(14-12-27)63-35-17-15-32-39-29(35)5-3-6-30(39)42(57)51(43(32)58)22-19-48-36(53)9-1-2-10-37(54)49-21-24-62-26-25-61-23-20-47-33-8-4-7-31-40(33)45(60)52(44(31)59)34-16-18-38(55)50-41(34)56/h3-8,11-15,17,34,47H,1-2,9-10,16,18-26H2,(H,48,53)(H,49,54)(H,50,55,56)
Chemical Name	N-[2-[6-(4-bromophenyl)sulfanyl-1,3-dioxobenzo[de]isoquinolin-2-yl]ethyl]-N'-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethyl]hexanediamide
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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
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

Targets	Bcl-2 3 μM (DC50) Bcl-2 4.94 μM (IC50) Mcl-1 11.81 μM (IC50)
References	[1]. Proteolysis Targeting Chimeras for the Selective Degradation of Mcl-1/Bcl-2 Derived from Nonselective Target Binding Ligands. J Med Chem. 2019 Aug 21.

Solubility Data

Solubility (In Vitro)

DMSO : 25 mg/mL (26.54 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.65 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 25.0 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.0618 mL	5.3088 mL	10.6175 mL
	5 mM	0.2124 mL	1.0618 mL	2.1235 mL
	10 mM	0.1062 mL	0.5309 mL	1.0618 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.