MYRIOCIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H39NO6
Molecular Weight	401.5375
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCCCC(=O)CCCCCC\C=C\C[C@@H](O)[C@H](O)[C@@](N)(CO)C(O)=O

InChI

InChIKey=ZZIKIHCNFWXKDY-GNTQXERDSA-N

InChI=1S/C21H39NO6/c1-2-3-4-10-13-17(24)14-11-8-6-5-7-9-12-15-18(25)19(26)21(22,16-23)20(27)28/h9,12,18-19,23,25-26H,2-8,10-11,13-16,22H2,1H3,(H,27,28)/b12-9+/t18-,19+,21+/m1/s1

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Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7794249
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18641634 | https://www.ncbi.nlm.nih.gov/pubmed/27621809 | https://www.ncbi.nlm.nih.gov/pubmed/17239824 | https://www.ncbi.nlm.nih.gov/pubmed/28474276

Myriocin ((2S,3R,4R,6E)-2-amino-3,4- dihydroxy-2-(hydroxymethyl)-14-oxo-6-eicosenoic acid, ISP-1, thermozymocidin) is a small-molecule immunosuppressant, isolated from the Mycelia sterilia thermophilic fungus. Myriocin inhibits serine palmitoyltransferase (SPT) at picomolar concentrations blocking synthesis of ceramide, a precursor of sphingomyelin (SM) and glycosphingolipids. Inhibition of hepatic serine palmitoyl transferase reduces plasma sphingomyelin levels in the absence of changes in cholesterol or triglyceride (TG) concentration and this leads to a reduction of atherosclerosis. In preclinical studies, Myriocin treated mice shows significant reductions in both plasma SM and Glycosphingolipids (GSL) concentration. Moreover, SM and GSL concentrations were significantly correlated, indicating that SPT inhibition suppresses the synthesis of both these sphingolipids concomitantly. The inhibition of atherosclerosis induced by myriocin was not associated with changes in plasma cholesterol or TG concentrations or lipoprotein profiles.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine palmitoyltransferase 1 2 Target ID: CHEMBL1250343 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7794249	Inhibitor 8297		0.28 nM [Ki]
Serine palmitoyltransferase 2 1 Target ID: CHEMBL1250344 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7794249	Inhibitor 8297		0.28 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Atherosclerosis 74 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17239824	Primary		Preclinical	Unknown Approved Use Unknown
Multiple sclerosis 104 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28474276	Primary		Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Serine palmitoyltransferase is the primary target of a sphingosine-like immunosuppressant, ISP-1/myriocin.	1995 Jun 15	7794249
gamma-Tocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting sphingolipid synthesis.	2004 Dec 21	15596715
Vorinostat and sorafenib increase ER stress, autophagy and apoptosis via ceramide-dependent CD95 and PERK activation.	2008 Oct	18787411
Resveratrol induced ER expansion and ER caspase-mediated apoptosis in human nasopharyngeal carcinoma cells.	2014 Mar	24264887

Patents

Sample Use Guides

In Vivo Use Guide

Mice were treated with 0.3 mg/kg every 48 h.

Route of Administration: Intraperitoneal

In Vitro Use Guide

Human oligodendroglioma cells were used for activity evaluation. Cells were grown to 70–80% confluent state and divided into four groups [Group # 1: untreated cells or control; Group # 2: cells treated with TNFα (100 ng/ml); Group # 3: cells treated with myriocin (5 µM), along with TNFα stimulation; and Group # 4: cells treated with TNFα, IFNγ, and combination of both cytokines (100 ng/ ml each) in presence and absence of myriocin(5 µM),]. After 24 h of incubation, cells were trypsinized, collected in cold PBS, and washed once with PBS. Lipids were extracted and ceramide purification was carried out. The protein content was measured by BCA (Pierce, Rockford, IL, USA) method.

Name

Type

Language

MYRIOCIN

Common Name

English

MYRIOCIN [MI]

Common Name

English

6-EICOSENOIC ACID, 2-AMINO-3,4-DIHYDROXY-2-(HYDROXYMETHYL)-14-OXO-, (2S,3R,4R,6E)

Systematic Name

English

ISP-1

Code

English

THERMOZYMOCIDIN

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/15/1449