ceramidase

Acid Ceramidase-IN-1 is a highly effective, orally bioavailable inhibitor of acid ceramidase (AC, ASAH-1) with an IC50 of 0.166 μM and exhibits exceptional brain penetration capabilities in mice.

Acid Ceramidase-IN-2 (compound 1), an acid ceramidase inhibitor, exhibits potentially antiproliferative and cytostatic effects. It is of interest due to the overexpression of human acid ceramidase in prostate cancer cells, suggesting potential anti-tumor efficacy. The hydrolysis of Acid Ceramidase-IN-2 can be inhibited by 3 a-ketoamides: GT85, GT98, and GT99 in vitro [1].

Endoglycoceramidase II (EGCase II), an endo-β-glucosidase, catalyzes the hydrolysis of the β-glycosidic linkage between oligosaccharides and ceramides in glycosphingolipids, releasing the complete glycan from ceramide [1] [2].

Endoglycoceramidase I (EGCase I), a glycosidase frequently utilized in biochemical studies, catalyzes a transglycosylation reaction. This process involves transferring the sugar moiety of GSLs to the primary hydroxyl group of various 1-alkanols [1].

Galactosylceramidase plays a role in the lysosomal catabolism of galactosylceramide. It can be utilized in research related to Krabbe disease.

Ceranib-2 (3-[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]-4-phenyl-1H-quinolin-2-one) is an inhibitor of ceramidase with an IC50 of 28 μM in SKOV3 cells. Ceranib-2 decreases levels of sphingosine and S1P, induces cell apoptosis and exhibits anticancer activity.

Ceranib1 is an inhibitor of ceramidase. It inhibits the proliferation of ovarian cancer cells. Ceranib1 inhibits ceramidase activity toward an exogenous ceramide analog, induces the accumulation of multiple ceramide species, decreases levels of S1P and sphingosine.

Sinbaglustat (OGT2378) (OGT2378) is a dual inhibitor of glucose ceramide synthetase (GCS) and non-lysosomal glucose ceramidase (GBA2).Sinbaglustat is an orally administered N-alkyl iminosugar that crosses the blood-brain barrier.Sinbaglustat is used for the treatment of lysosomal storage disorders and for the study of central neurodegenerative disorders associated with lysosomal dysfunction. Sinbaglustat is used for the treatment of lysosomal storage disorders and for the study of lysosomal dysfunction-related central neurodegenerative diseases.

Carmofur (HCFU) is a highly potent acid ceramidase inhibitor, used in the treatment of breast and colorectal cancer. Carmofur has been known to induce leukoencephalopathy.

LCL521 inhibits lysosomal acid sphingomyelinase (ASMase).LCL521 is an acid ceramidase (ACDase) inhibitor.

LCL521 dihydrochloride is a compound that functions as an inhibitor of both acid ceramidase (ACDase) and lysosomal acid sphingomyelinase (ASMase).

Antifungalagent 117 is a bipyrrole carboxamide derivative with antifungal activity, exhibiting an EC50 value of 11.58 mg L against Sclerotinia sclerotiorum. This compound induces cell death by increasing cell membrane permeability, causing an imbalance in osmotic pressure between the interior and exterior of the cell. It also promotes oxidative damage to the cell membrane by inducing the accumulation of reactive oxygen species (ROS), leading to the leakage of cellular contents. RNA sequencing analysis has demonstrated that Antifungalagent 117 disrupts cell membrane structure by downregulating catalase genes and upregulating neutral ceramidase genes, accelerating ceramide metabolism and hastening cell death. The compound holds significant potential for application in plant protection and the control of fungal infections.

ARN14974 is a benzoxazolone carboxamide. ARN14974 is a potent inhibitor of acid ceramidase with IC50 of 79 nM[1].

D-NMAPPD ((1R,2R)-B13) is an acid ceramidase inhibitor and ceramide analog with potential antiproliferative activity that modulates ceramide signaling in human melanoma cells. D-NMAPPD is used in the study of colon cancer.

C6 urea ceramide is an inhibitor of neutral ceramidase.1 It increases total ceramide levels in wild-type mouse embryonic fibroblasts (MEFs) and in HT-29 colon cancer cells but not in MEFs lacking neutral ceramidase. It inhibits proliferation of, and induces apoptosis and autophagy in HT-29, but not non-cancerous RIE-1, cells when used at concentrations of 5 and 10 μM. C6 urea ceramide decreases total β-catenin, increases phosphorylated β-catenin, and induces colocalization of β-catenin with the 20S proteasome in HT-29 and HCT116, but not RIE-1, cells. It reduces tumor growth and increases C16, C18, C20, and C24 ceramide levels in tumor tissue in an HT-29 mouse xenograft model when administered at doses of 1.25, 2.5, and 5 mg/kg for five days. |1. García-Barros, M., Coant, N., Kawamori, T., et al. Role of neutral ceramidase in colon cancer. FASEB J. 30(12), 4159-4171 (2016).

ARN14988 is a potent inhibitor of acid ceramidase (IC50 = 12.8 nM for the human enzyme). It inhibits acid ceramidase activity and increases levels of C16 dihydro ceramide and C16 ceramide in A375, G361, M14, MeWo, MNT-1, and SK-MEL-28 melanoma cells. ARN14988 also reduces growth of A375 and G361 melanoma cells (EC50s = 41.8 and 67.7 μM, respectively).

D-erythro-MAPP (D-e-MAPP) is a ceramidase inhibitor, a ceramide analog with potential anticancer activity.

C18 D-threoCeramide (d18:1 18:0) is a synthetic ceramide and stereoisomer of C18 ceramide .1It inhibits rat brain mitochondrial ceramidase (mt-CDase) with an IC50value of 16.6 μM.2[Matreya, LLC. Catalog No. 1855] 1.Koolath, S., Murai, Y., Suga, Y., et al.Chiral combinatorial preparation and biological evaluation of unique ceramides for inhibition of sphingomyelin synthaseChirality32(3)308-313(2019) 2.Usta, J., El Bawab, S., Roddy, P., et al.Structural requirements of ceramide and sphingosine based inhibitors of mitochondrial ceramidaseBiochemistry40(32)9657-9668(2001)

C18 L-threo Ceramide is a synthetic ceramide and stereoisomer of C18 ceramide that has been used for structural characterization of natural sphingolipids. It inhibits rat brain mitochondrial ceramidase (mt-CDase) with an IC50 value of 0.21 mol% (16.8 μM).

SABRAC inhibits acid ceramidase in PC3 MC metastatic prostate cancer cells (IC50 = <1 µM), as well as induces accumulation of ceramides in the same cells.

C16-Urea-Ceramide s a neutral ceramidase (nCDase) inhibitor. It is a bioactive ceramide.

SOCLAC, a derivative of the acid ceramidase inhibitor SABRAC, functions as an irreversible inhibitor of acid ceramidase with an inhibition constant (Ki) of 40.2 nM.

SOBRAC, a derivative of the acid ceramidase inhibitor SABRAC, acts as an irreversible inhibitor of acid ceramidase (Ki= 29.7 nM).

W000113414_I13 serves as an acid ceramidase (AC) inhibitor, demonstrating dose-dependent inhibition with an IC50 of 6.6 μM. It is applicable for cancer research [1].