UGT8-IN-1 is a BBB (blood-brain barrier) permeable (penetrable), orally bioactive inhibitor of ceramide galactosyltransferase (UGT8) and may be utilized in the study of lysosomal storage disorders.

Physicochemical Properties

Molecular Formula	C20H22F6N4O4S
Molecular Weight	528.47
Exact Mass	528.126
CAS #	2414349-93-0
PubChem CID	146490788
Appearance	White to off-white solid powder
LogP	4.3
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	13
Rotatable Bond Count	7
Heavy Atom Count	35
Complexity	750
Defined Atom Stereocenter Count	1
SMILES	C(OC1CCN(C2N=C3C(C(NC)=O)=CSC3=C(C(F)(F)F)C=2)CC1)(=O)N[C@@H](C)COC(F)(F)F
InChi Key	UQQUABVWYAPTIQ-JTQLQIEISA-N
InChi Code	InChI=1S/C20H22F6N4O4S/c1-10(8-33-20(24,25)26)28-18(32)34-11-3-5-30(6-4-11)14-7-13(19(21,22)23)16-15(29-14)12(9-35-16)17(31)27-2/h7,9-11H,3-6,8H2,1-2H3,(H,27,31)(H,28,32)/t10-/m0/s1
Chemical Name	[1-[3-(methylcarbamoyl)-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]piperidin-4-yl] N-[(2S)-1-(trifluoromethoxy)propan-2-yl]carbamate
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 Vivo

UGT8-IN-1 (compound 19) administered intravenously (1 mg/kg) to rats, mice, and dogs, respectively, showed T1/2 values of 4.3 h, 1.13 h, and 13.6 h. After being administered orally (3 mg/kg) to rats, mice, and dogs, respectively, UGT8-IN-1 (compound 19) exhibits F% of 40%, 34%, and 52%[1]. Administered orally twice daily for three days, compound 19, UGT8-IN-1, exhibits ≥90% inhibition of 13C-Gal incorporation into GalCer and SFT at all three tested doses; the estimated ED50s for both SFT and GalCer inhibition are less than 3 mg/kg. Over 99% of plasma proteins and tissues are bound by compound 19, or UGT8-IN-1[1].

References

[1]. Brain Penetrable Inhibitors of Ceramide Galactosyltransferase for the Treatment of Lysosomal Storage Disorders. ACS Med Chem Lett. 2020 Jun 16;11(10):2010-2016.

Solubility Data

Solubility (In Vitro)

DMSO: 115 mg/mL (217.61 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5.75 mg/mL (10.88 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 57.5 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	1.8923 mL	9.4613 mL	18.9226 mL
	5 mM	0.3785 mL	1.8923 mL	3.7845 mL
	10 mM	0.1892 mL	0.9461 mL	1.8923 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.