(S,R,S)-AHPC-C6-PEG3-C4-Cl is a composite molecule connected by E3 ligand to 20 atoms, and the linker of the linker is a Halogen group. (S,R,S)-AHPC-C6-PEG3-C4-Cl contains VHL ligands based on (S,R,S)-AHPC and based on an alkyl/ether linker. (S,R,S)-AHPC-C6-PEG3-C4-Cl can induce the degradation of GFP-HaloTag7.

Physicochemical Properties

Molecular Formula	C38H59CLN4O7S
Molecular Weight	751.415668725967
Exact Mass	750.379
CAS #	1835705-55-9
PubChem CID	129072788
Appearance	Light yellow to yellow ointment
LogP	4.9
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	25
Heavy Atom Count	51
Complexity	1010
Defined Atom Stereocenter Count	3
SMILES	CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCOCCOCCOCCCCCCCl)O
InChi Key	MLRLOIWXHCPWFF-MEEYNGGZSA-N
InChi Code	InChI=1S/C38H59ClN4O7S/c1-28-34(51-27-41-28)30-15-13-29(14-16-30)25-40-36(46)32-24-31(44)26-43(32)37(47)35(38(2,3)4)42-33(45)12-8-7-11-19-49-21-23-50-22-20-48-18-10-6-5-9-17-39/h13-16,27,31-32,35,44H,5-12,17-26H2,1-4H3,(H,40,46)(H,42,45)/t31-,32+,35-/m1/s1
Chemical Name	(2S,4R)-1-[(2S)-2-[6-[2-[2-(6-chlorohexoxy)ethoxy]ethoxy]hexanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-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

(S,R,S)-AHPC-C6-PEG3-C4-Cl employs the cereblon ligand [1]. The linker is 6-2-2-6. The linkers comprise a combination of hydrophobic and hydrophilic moieties that balance the hydrophobicity and hydrophilicity of the resulting hybrid molecules. PROTACs that cause the degradation of BCR-ABL, an oncogenic tyrosine kinase, have been created. (S,R,S)-AHPC-C6-PEG3-C4-Cl can be linked to potent TKIs (bosutinib and dasatinib), which degrade c-ABL and BCR-ABL by hijacking either the CRBN or VHL E3 ubiquitin ligase [2].

References

[1]. Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL. Angew Chem Int Ed Engl. 2016 Jan 11;55(2):807-10. [2]. US 20170121321 A1.

Solubility Data

Solubility (In Vitro)

Ethanol : ~100 mg/mL (~133.08 mM) DMSO : ≥ 100 mg/mL (~133.08 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.33 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 (3.33 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	1.3308 mL	6.6541 mL	13.3081 mL
	5 mM	0.2662 mL	1.3308 mL	2.6616 mL
	10 mM	0.1331 mL	0.6654 mL	1.3308 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.