THP-PEG4-Pyrrolidine(N-Me)-CH2OH is a PROTAC (PROteolysis TArgeting Chimera) linker based on PEG structure, which may be utilized to prepare PROTAC K-Ras Degrader-1 .

Physicochemical Properties

Molecular Formula	C₁₉H₃₇NO₇
Molecular Weight	391.50
Exact Mass	391.257
CAS #	2378261-81-3
PubChem CID	139579035
Appearance	Colorless to light yellow liquid
LogP	0
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	15
Heavy Atom Count	27
Complexity	361
Defined Atom Stereocenter Count	2
SMILES	CN1C[C@@H](C[C@H]1CO)OCCOCCOCCOCCOC2CCCCO2
InChi Key	WSIXZTYJDDDXDX-PAMZHZACSA-N
InChi Code	InChI=1S/C19H37NO7/c1-20-15-18(14-17(20)16-21)25-12-10-23-8-6-22-7-9-24-11-13-27-19-4-2-3-5-26-19/h17-19,21H,2-16H2,1H3/t17-,18+,19?/m0/s1
Chemical Name	[(2S,4R)-1-methyl-4-[2-[2-[2-[2-(oxan-2-yloxy)ethoxy]ethoxy]ethoxy]ethoxy]pyrrolidin-2-yl]methanol
Synonyms	THP PEG4 Pyrrolidine(NMe)CH2OH THP PEG4 Pyrrolidine(N Me) CH2OH
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	In SW1573 cells, PROTAC K-Ras Degrader-1, a strong K-Ras degrader-based PROTAC, demonstrates ≥70% degradation efficacy[1]. A linker separates the two ligands that make up PROTACs; one ligand is for an E3 ubiquitin ligase, and the other is for the target protein. Target proteins are specifically broken down by PROTACs by taking advantage of the intracellular ubiquitin-proteasome system.
References	[1]. MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE. WO2019195609A2.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~255.43 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.39 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 (6.39 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.39 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 25.0 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	2.5543 mL	12.7714 mL	25.5428 mL
	5 mM	0.5109 mL	2.5543 mL	5.1086 mL
	10 mM	0.2554 mL	1.2771 mL	2.5543 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.