PROTAC SGK3 degrader-1 (SGK3-PROTAC1) is a PROTAC-based degrader of SKG3 (Serum/Glucocorticoid Regulated Kinase Family Member 3), inducing 50% degradation of endogenous SGK3 in 2 hours, with maximal 80% degradation occurred within 8 hours, accompanied by a loss of phosphorylation of NDRG1 (an SGK3 substrate).

Physicochemical Properties

Molecular Formula	C57H73FN10O11S2
Molecular Weight	1157.37833476067
Exact Mass	1156.488
CAS #	2381320-35-8
PubChem CID	139035049
Appearance	White to off-white solid powder
LogP	6
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	19
Rotatable Bond Count	29
Heavy Atom Count	81
Complexity	2050
Defined Atom Stereocenter Count	4
SMILES	S1C=NC(C)=C1C1C=CC(=CC=1)CNC([C@@H]1C[C@H](CN1C([C@H](C(C)(C)C)NC(COCCOCCOCCCCCCN1CCO[C@@H](COC2C3C=NNC=3N=C(C3C=CC(=CC=3)NS(C3C(=CC=C(C)C=3)F)(=O)=O)N=2)C1)=O)=O)O)=O
InChi Key	RTFQFPZKDYMMMJ-RIAKQDHQSA-N
InChi Code	InChI=1S/C57H73FN10O11S2/c1-37-10-19-46(58)48(28-37)81(73,74)66-42-17-15-41(16-18-42)52-63-53-45(31-61-65-53)55(64-52)79-34-44-33-67(21-23-78-44)20-8-6-7-9-22-75-24-25-76-26-27-77-35-49(70)62-51(57(3,4)5)56(72)68-32-43(69)29-47(68)54(71)59-30-39-11-13-40(14-12-39)50-38(2)60-36-80-50/h10-19,28,31,36,43-44,47,51,66,69H,6-9,20-27,29-30,32-35H2,1-5H3,(H,59,71)(H,62,70)(H,61,63,64,65)/t43-,44-,47+,51-/m1/s1
Chemical Name	(2S,4R)-1-[(2S)-2-[[2-[2-[2-[6-[(2R)-2-[[6-[4-[(2-fluoro-5-methylphenyl)sulfonylamino]phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxymethyl]morpholin-4-yl]hexoxy]ethoxy]ethoxy]acetyl]amino]-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 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	When coupled with GDC0941, PROTAC SGK3 degrader-1 (SGK3-PROTAC1) (0.3 μM, 4 weeks) suppresses the development of CAMA-1 or ZR-75-1 cells [1]. Within HEK293 cells, PROTAC SGK3 degrader-1 (0.1 μM, 48 h) 2 decreases SGK3 levels by 65% while leaving SGK1, SGK2, and S6K1 expression levels unchanged [1]. In HEK293 cells, PROTAC SGK3 degrader-1 (1–10 μM, 48 h) regulates the decrease in S6K1 levels [1]. SGK3 degrader-1 (>0.1 μM, 8 h) can promote SGK3 phosphorylation in CAMA-1 and ZR-75-1 cells and diminish NDRG1 phosphorylation in HEK293 cells, but not SGK1 or S6K phosphorylation [1].
Cell Assay	Cell viability assay [1] Cell Types: CAMA-1 or ZR-75-1 Cell Tested Concentrations: 0.3 μM Incubation Duration: 4 weeks Experimental Results: Cell growth can be inhibited when used in combination with GDC0941. Western Blot Analysis[1] Cell Types: HEK293 Cell Tested Concentrations: 0.1 μM Incubation Duration: 48 hrs (hours) Experimental Results: 65% reduction in SGK3 levels without affecting SGK1, SGK2 or S6K1.
References	[1]. Design and Characterization of SGK3-PROTAC1, an Isoform Specific SGK3 Kinase PROTAC Degrader. ACS Chem Biol. 2019 Sep 20;14(9):2024-2034.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 100 mg/mL (~86.40 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.16 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 (2.16 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	0.8640 mL	4.3201 mL	8.6402 mL
	5 mM	0.1728 mL	0.8640 mL	1.7280 mL
	10 mM	0.0864 mL	0.4320 mL	0.8640 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.