Glucosylceramide synthase-IN-1 (T-036) is a potent, BBB (blood-brain barrier)-crossing, and orally bioactive glucosylceramide synthase (GCS) inhibitor (antagonist) with IC50 of 31 nM for human GCS and mouse GCS respectively. and 51 nM. Glucosylceramide synthase-IN-1 may be used in Gaucher disease study.

Physicochemical Properties

Molecular Formula	C24H20F4N2O3
Molecular Weight	460.420820236206
Exact Mass	460.141
CAS #	2601393-20-6
PubChem CID	155595464
Appearance	White to off-white solid powder
LogP	4
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	5
Heavy Atom Count	33
Complexity	696
Defined Atom Stereocenter Count	0
SMILES	C1(C2=CC=C(F)C=C2OCC(F)(F)F)=NC=CC2C(=O)N(C3=CC=C(C(O)(C)C)C=C3)CC1=2
InChi Key	OAZAPIKYVGRNCO-UHFFFAOYSA-N
InChi Code	InChI=1S/C24H20F4N2O3/c1-23(2,32)14-3-6-16(7-4-14)30-12-19-17(22(30)31)9-10-29-21(19)18-8-5-15(25)11-20(18)33-13-24(26,27)28/h3-11,32H,12-13H2,1-2H3
Chemical Name	4-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]-2-[4-(2-hydroxypropan-2-yl)phenyl]-3H-pyrrolo[3,4-c]pyridin-1-one
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 and light.
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	In Gaucher disease fibroblasts, glucosylceramide synthase-IN-1 (T-036) efficiently decreases GCS production and catalyzes the synthesis of glucosylceramide (GlcCer) at an EC50 of 7.6 nM [1].
ln Vivo	Glucosylceramide synthase-IN-1 (T-036) has good oral exposure (BA = 67%) and moderate brain penetration (Kpuu,brain = 0.11). A single dosage of glucosylceramide synthase-IN-1 (T-036) reduced GlcCer in the plasma and cerebral cortex of wild-type mice, while 2-month administration of glucosylceramide synthase-IN-1 (T-036) reduced GlcCer in the plasma and cerebral cortex of wild-type mice. Significantly reduced glucosylsphingosine (GlcSph) in the cerebral cortex of a Gaucher disease animal model [1].
References	[1]. Discovery of Brain-Penetrant Glucosylceramide Synthase Inhibitors with a Novel Pharmacophore. J Med Chem. 2022 Mar 10;65(5):4270-4290.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~217.19 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1719 mL	10.8596 mL	21.7193 mL
	5 mM	0.4344 mL	2.1719 mL	4.3439 mL
	10 mM	0.2172 mL	1.0860 mL	2.1719 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.