HaloPROTAC-E is a new type of Halo PROTAC highly efficient degrader that can induce the reversible degradation of two endosomal localized proteins, SGK3 and VPS34. Its DC50 is 3-10 nM and only significantly and selectively induces the Halo-tagged endogenous VPS34 complex. degradation of compounds (VPS34, VPS15, Beclin1 and ATG14).

Physicochemical Properties

Molecular Formula	C39H56CLN5O8S
Molecular Weight	790.408648490906
Exact Mass	789.353
CAS #	2365478-58-4
PubChem CID	154723985
Appearance	Colorless to light yellow ointment
LogP	4.1
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	24
Heavy Atom Count	54
Complexity	1250
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)C4(CC4)C#N)O)OCCOCCOCCOCCCCCCCl
InChi Key	NJCGXLMTZGCSRS-JSWXEYCZSA-N
InChi Code	InChI=1S/C39H56ClN5O8S/c1-27-33(54-26-43-27)28-9-10-29(32(21-28)53-20-19-52-18-17-51-16-15-50-14-8-6-5-7-13-40)23-42-35(47)31-22-30(46)24-45(31)36(48)34(38(2,3)4)44-37(49)39(25-41)11-12-39/h9-10,21,26,30-31,34,46H,5-8,11-20,22-24H2,1-4H3,(H,42,47)(H,44,49)/t30-,31+,34-/m1/s1
Chemical Name	(2S,4R)-N-[[2-[2-[2-[2-(6-chlorohexoxy)ethoxy]ethoxy]ethoxy]-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-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

References

[1]. Rapid and Reversible Knockdown of Endogenously Tagged Endosomal Proteins via an Optimized HaloPROTAC Degrader. ACS Chem Biol. 2019;14(5):882-892.

Solubility Data

Solubility (In Vitro)

DMSO : 100 mg/mL (126.52 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.16 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 (3.16 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	1.2652 mL	6.3258 mL	12.6517 mL
	5 mM	0.2530 mL	1.2652 mL	2.5303 mL
	10 mM	0.1265 mL	0.6326 mL	1.2652 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.