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Merck
CN

SML4003

Sigma-Aldrich

TP-060

≥98% (HPLC)

Synonym(s):

2-(4-Fluoro-2-(2,2,2-trifluoroethoxy)phenyl)-8-(4-(1-hydroxy-1-methylethyl)phenyl)-3,8-diaza-bicyclo[4.3.0]nona-1(6),2,4-trien-7-one, 4-[4-Fluoro-2-(2,2,2-trifluoroethoxy)phenyl]-2,3-dihydro-2-[4-(1-hydroxy-1-methylethyl)phenyl]-1H-pyrrolo[3,4-c]pyridin-1-one, 4-[4-Fluoro-2-(2,2,2-trifluoroethoxy)phenyl]-2-[4-(2-hydroxypropan-2-yl)phenyl]-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one, Glucosylceramide synthase-IN-1, T 036, T-036, T036, TP 060, TP060

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About This Item

Empirical Formula (Hill Notation):
C24H20F4N2O3
CAS Number:
Molecular Weight:
460.42
MDL number:
UNSPSC Code:
12352202
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Quality Level

Assay

≥98% (HPLC)

form

powder

color

white to beige

solubility

DMSO: 2 mg/mL, clear (Warmed)

storage temp.

2-8°C

SMILES string

O=C1C2=C(CN1C3=CC=C(C(C)(C)O)C=C3)C(C4=C(OCC(F)(F)F)C=C(F)C=C4)=NC=C2

InChI key

OAZAPIKYVGRNCO-UHFFFAOYSA-N

Biochem/physiol Actions

Orally active, brain-penetrant, substrate-noncompetitive glucosylceramide synthase (GCS) inhibitor with therapeutic efficacy in a murine Gaucher’s disease (GD) model in vivo.
TP-060 (T-036) is an orally active, brain-penetrant, substrate-noncompetitive, potent and selective glucosylceramide synthase (GCS) inhibitor (human/mouse IC50 = 31/51 nM) that effectively downregulates glucosylceramide (GlcCer) level in GBA mutant human fibroblasts containing mutated glucosylceramidase (IC50 = 7.6 nM). TP-060 is efficacious in lowering both GlcCer and glucosylsphingosine (GlcSph) levels in the plasma and cerebral cortex of Gba D409V KI mice in vivo following a two-month treatment in the murine Gaucher’s disease (GD) model (10 and 30 mg/kg/day p.o.).

Storage Class Code

11 - Combustible Solids

Flash Point(F)

Not applicable

Flash Point(C)

Not applicable

Regulatory Information

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Yuta Tanaka et al.
Journal of medicinal chemistry, 65(5), 4270-4290 (2022-02-22)
Inhibition of glucosylceramide synthase (GCS) is a major therapeutic strategy for Gaucher's disease and has been suggested as a potential target for treating Parkinson's disease. Herein, we report the discovery of novel brain-penetrant GCS inhibitors. Assessment of the structure-activity relationship
Junsi Wang et al.
Bioorganic & medicinal chemistry letters, 77, 129039-129039 (2022-11-08)
Glucosylceramide synthase (GCS) has drawn much attention as an attractive protein target in the disease pathways of Parkinson's Disease (PD) and lysosomal storage disorders, such as Gaucher's Disease (GD). In previous our study, T-036 and its analogue, 2a, were discovered
Takahiro Fujii et al.
Journal of neurochemistry, 159(3), 543-553 (2021-08-17)
Gaucher disease (GD), the most common lysosomal storage disorders, is caused by GBA gene mutations resulting in glycosphingolipids accumulations in various tissues, such as the brain. While suppressing glycosphingolipid accumulation is the central strategy for treating peripheral symptoms of GD

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