NQTrp, an aromatic naphthoquinone-tryptophan hybrid molecule, is an inhibitor (blocker/antagonist) of tau protein aggregation and has anti-amyloid activity. NQTrp inhibits the in vitro aggregation of hexapeptide (41GCWMLY46, N-terminus of γD-crystallin) and full-length γD-crystallin.

Physicochemical Properties

Molecular Formula	C21H16N2O4
Molecular Weight	360.36
Exact Mass	360.111
CAS #	185351-19-3
PubChem CID	56605052
Appearance	Brown to wine solid powder
LogP	3.107
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	5
Heavy Atom Count	27
Complexity	659
Defined Atom Stereocenter Count	1
SMILES	C1=CC=C2C(=C1)C(=O)C=C(C2=O)N[C@@H](CC3=CNC4=CC=CC=C43)C(=O)O
InChi Key	DZZUYZXINNHEGM-SFHVURJKSA-N
InChi Code	InChI=1S/C21H16N2O4/c24-19-10-17(20(25)15-7-2-1-6-14(15)19)23-18(21(26)27)9-12-11-22-16-8-4-3-5-13(12)16/h1-8,10-11,18,22-23H,9H2,(H,26,27)/t18-/m0/s1
Chemical Name	(2S)-2-[(1,4-dioxonaphthalen-2-yl)amino]-3-(1H-indol-3-yl)propanoic acid
Synonyms	NQ Trp; NQ-Trp; NQTrp
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: This product requires protection from light (avoid light exposure) during transportation and storage.
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

GDC6 peptide fibrils (50 μM) were observed in TEM examination when NQTrp was present in a 5:1, 1:1, or 1:5 ratio (GDC6: NQTrp). NQTrp blocks the production of elongated amyloid fibrils and, in a dose-dependent manner, efficiently suppresses fibrillation with GDC6 peptide (50 μM) [1]. NQTrp decreases the cytotoxicity caused by hexapeptide aggregates in ARPE-19 cells (IC50=70 μM) and has no harmful effects on retinal cell cultures [1].

References

[1]. An amyloidogenic hexapeptide from the cataract-associated γD-crystallin is a model for the full-length protein and is inhibited by naphthoquinone-tryptophan hybrids. Int J Biol Macromol. 2020 Aug 15;157:424-433.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~346.88 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.77 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 20.8 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: ≥ 2.08 mg/mL (5.77 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 20.8 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	2.7750 mL	13.8750 mL	27.7500 mL
	5 mM	0.5550 mL	2.7750 mL	5.5500 mL
	10 mM	0.2775 mL	1.3875 mL	2.7750 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.