(S,R,S)-AHPC-C8-NH2 (VH032-C8-NH2) is a synthetic E3 ligase (e.g. CRBN) ligand-linker conjugate containing VH032-based VHL ligand and 1 linker. (S,R,S)-AHPC-C8-NH2 may be utilized to prepare PROTAC degraders targeting AKT, Example 8, XF038-164A, found in patent document WO2019173516A1.

Physicochemical Properties

Molecular Formula	C31H48CLN5O4S
Molecular Weight	622.261925697327
Exact Mass	585.334
CAS #	2341796-79-8
Related CAS #	(S,R,S)-AHPC-C8-NH2 dihydrochloride;2341796-80-1;(S,R,S)-AHPC-C8-NH2 hydrochloride;2376139-49-8
PubChem CID	138991798
Appearance	Light yellow to yellow solid powder
LogP	4
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	15
Heavy Atom Count	41
Complexity	845
Defined Atom Stereocenter Count	3
SMILES	Cl.S1C=NC(C)=C1C1C=CC(=CC=1)CNC([C@@H]1C[C@H](CN1C([C@H](C(C)(C)C)NC(CCCCCCCCN)=O)=O)O)=O
InChi Key	QLJZVMJBYNFUSG-CERRFVOPSA-N
InChi Code	InChI=1S/C31H47N5O4S/c1-21-27(41-20-34-21)23-14-12-22(13-15-23)18-33-29(39)25-17-24(37)19-36(25)30(40)28(31(2,3)4)35-26(38)11-9-7-5-6-8-10-16-32/h12-15,20,24-25,28,37H,5-11,16-19,32H2,1-4H3,(H,33,39)(H,35,38)/t24-,25+,28-/m1/s1
Chemical Name	(2S,4R)-1-[(2S)-2-(9-aminononanoylamino)-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

Targets	VHL
ln Vitro	One ligand is for an E3 ubiquitin ligase, and the other is for the target protein; these two ligands are joined by a linker to form PROTACs. PROTACs target and selectively degrade target proteins by taking advantage of the intracellular ubiquitin-proteasome system.
References	[1]. Serine threonine kinase (akt) degradation / disruption compounds and methods of use. Patent WO2019173516A1.

Solubility Data

Solubility (In Vitro)

DMSO :≥ 100 mg/mL (~170.71 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.27 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 (4.27 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 (4.27 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	1.6070 mL	8.0352 mL	16.0705 mL
	5 mM	0.3214 mL	1.6070 mL	3.2141 mL
	10 mM	0.1607 mL	0.8035 mL	1.6070 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.