PROTAC K-Ras Degrader-1 (compound 518 extracted from WO2019195609A2) is novel and potent K-Ras degrader based on PROTAC technology, which exhibits ≥70% degradation efficacy in SW1573 cells.

Physicochemical Properties

Molecular Formula	C53H62N10O10
Molecular Weight	999.12039232254
CAS #	2378258-52-5
PubChem CID	139579413
Appearance	Light yellow to yellow solid powder
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	17
Rotatable Bond Count	22
Heavy Atom Count	73
Complexity	1970
Defined Atom Stereocenter Count	3
SMILES	O(CCOCCOCCOCCNC1=CC=CC2C(N(C(C=21)=O)C1C(NC(CC1)=O)=O)=O)[C@H]1CN(C)[C@H](COC2=NC3CN(C4=CC=CC5C=CC=CC4=5)CCC=3C(=N2)N2CCN(C(C=C)=O)[C@@H](CC#N)C2)C1
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

ln Vitro	Two distinct ligands, one for the E3 ubiquitin ligase and the other for the target protein, are present in PROTAC and are joined by a linker. Target proteins are broken down by PROTAC through the intracellular ubiquitin-proteasome system coupling [1].
References	[1]. MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE. WO2019195609A2.

Solubility Data

Solubility (In Vitro)

DMSO : ~33.33 mg/mL (~33.36 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.50 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 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.50 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 25.0 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.0009 mL	5.0044 mL	10.0088 mL
	5 mM	0.2002 mL	1.0009 mL	2.0018 mL
	10 mM	0.1001 mL	0.5004 mL	1.0009 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.