L-threo-Dihydrosphingosine

Name: L-threo-Dihydrosphingosine
SKU: ACM15639506
Rating: 5 (1 reviews)

CAS

15639-50-6

Catalog Number

ACM15639506

Category

Main Products

Molecular Weight

301.0

Molecular Formula

C18H39NO2

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Specification

Synonyms

L-threo-Sphinganine

Melting Point

103 - 114 °C

Appearance

Solid

How L-threo-sphinganine Induces Autophagy in Solid Tumor Cells?

Coward, Jesse, et al. Autophagy, 2009, 5(2), 184-193.

L-threo-sphinganine (safingol), a L-threo stereoisomer of endogenous (D-erythro) sphingosine, is an in vitro inhibitor of protein kinase C and sphingosine kinase. In this work, it was found that l-threo-sphinganine drives autophagy directly by blocking PKCs and PI3k, not by changing native sphingolipids.
Mechanism of Action
· Safingol inhibits PKCβ-I, PKCδ, and PKCε, as well as the phosphorylation of key components in the PI3K/Akt/mTOR pathway (including Akt, p70S6k, and rS6) and the MAPK pathway (ERK). While blocking PI3K with LY294002 or silencing PKCδ and PKCε using siRNA in HCT-116 cells promotes autophagy, the effect is less pronounced than that caused by safingol. In contrast, activating PKCs with phorbol 12,13-dibutyrate (PDBu) or introducing a constitutively active form of Akt diminishes safingol's autophagic effect, although not entirely, suggesting that both Akt- and PKC-dependent pathways partially and independently contribute to safingol-induced autophagy.
· Notably, combining siRNA-mediated depletion of PKCε with LY294002 inhibition of PI3K produces a level of autophagy similar to that induced by safingol. Liquid chromatography and electrospray tandem mass spectrometry analyses revealed that safingol does not increase the levels of any known endogenous sphingolipids (such as ceramide, sphingosine-1-phosphate, and dihydroceramide) that are known to promote autophagy, indicating that these effects may stem from safingol itself or another metabolite.

Safingol Combined with Cisplatin for Advanced Solid Tumors

Dickson, Mark A., et al. Clinical Cancer Research, 2011, 17(8), 2484-2492.

Safingol (l-threo-dihydrosphingosine) is a putative inhibitor of SphK. In this work, a phase I trial of safingol (S) alone and in combination with cisplatin (C) was conducted. The results showed that Safingol can be safely used in combination with cisplatin. Reversible dose-dependent hepatotoxicity was observed. Safingol achieved targeted inhibition by downregulating S1P.
Evaluation of results
A total of 43 patients underwent treatment, with 41 assessed for toxicity and 37 for response. The maximum tolerated dose (MTD) was 840 mg/m² of S administered over 120 minutes, combined with 60 mg/m² of C, every three weeks. Dose-limiting toxicities (DLTs) associated with cisplatin included fatigue and hyponatremia, while S caused elevated hepatic enzymes. The pharmacokinetics of S were linear across the dosage range, showing no significant interaction with C. Patients receiving doses at or near the MTD exhibited S levels exceeding 20 μmol/L, maintaining levels of at least 5 μmol/L for four hours. The most favorable outcomes included stable disease in six patients, lasting an average of 3.3 months (ranging from 1.8 to 7.2 months). One patient with adrenal cortical cancer experienced significant regression of liver and lung metastases, while another had prolonged stable disease. Additionally, S was linked to a dose-dependent decrease in plasma S1P levels.

What is the molecular formula of L-threo-Dihydrosphingosine?

The molecular formula of L-threo-Dihydrosphingosine is C18H39NO2.

What are the synonyms for L-threo-Dihydrosphingosine?

The synonyms for L-threo-Dihydrosphingosine include SAFINGOL, 15639-50-6, and (2S,3S)-2-aminooctadecane-1,3-diol.

What is the molecular weight of L-threo-Dihydrosphingosine?

The molecular weight of L-threo-Dihydrosphingosine is 301.5 g/mol.

What is the structure of L-threo-Dihydrosphingosine?

The structure of L-threo-Dihydrosphingosine is a saturated derivative of sphingosine.

What is the IUPAC name of L-threo-Dihydrosphingosine?

The IUPAC name of L-threo-Dihydrosphingosine is (2S,3S)-2-aminooctadecane-1,3-diol.

What is the InChI key of L-threo-Dihydrosphingosine?

The InChI key of L-threo-Dihydrosphingosine is OTKJDMGTUTTYMP-ROUUACIJSA-N.

What is the CAS number of L-threo-Dihydrosphingosine?

The CAS number of L-threo-Dihydrosphingosine is 15639-50-6.

What is the UNII of L-threo-Dihydrosphingosine?

The UNII of L-threo-Dihydrosphingosine is OWA98U788S.

What is the ChEMBL ID of L-threo-Dihydrosphingosine?

The ChEMBL ID of L-threo-Dihydrosphingosine is CHEMBL1442934.

What are the physical properties of L-threo-Dihydrosphingosine?

The physical properties of L-threo-Dihydrosphingosine include a molecular weight of 301.5 g/mol, an XLogP3-AA value of 5.8, a hydrogen bond donor count of 3, and a hydrogen bond acceptor count of 3.