Thiolutin

Names

[ CAS No. ]:
87-11-6

[ Name ]:
Thiolutin

[Synonym ]:
acetopyrrothine
N-(4-Methyl-5-oxo-4,5-dihydro[1,2]dithiolo[4,3-b]pyrrol-6-yl)acetamide
N-(4-methyl-5-oxo-4,5-dihydro-[1,2]dithiolo[4,3-b]pyrrol-6-yl)-acetamide
6-(Acetylamino)-4-methyl-1,2-dithiolo(4,3-b)pyrrol-5(4H)-one
6-Acetamido-4-methyl-1,2-dithiolo<4,3-b>pyrrol-5(4H)-on
Acetopyrrothin
6-Acetamido-4-methyl-1,2-dithiolo(4,3-b)pyrrol-5(4H)-one
6-(Acetamido)-4-methyl-1,2-dithiolo[4,3-b]pyrrol-5(4H)-one
MFCD07370147
3-Acetamido-5-methylpyrrolin-4-one[4,3-d]-1,2-dithiole
Acetamide, N-(4,5-dihydro-4-methyl-5-oxo-1,2-dithiolo[4,3-b]pyrrol-6-yl)-
Thiolutin
N-(4-Methyl-5-oxo-4,5-dihydro-[1,2]dithiolo[4,3-b]pyrrol-6-yl)-acetamid
3-Acetamido-5-methylpyrrolin-4-one(4,3-d)-1,2-dithiole
6-acetylamino-4-methyl-4H-[1,2]dithiolo[4,3-b]pyrrol-5-one

Biological Activity

[Description]:

Thiolutin (Acetopyrrothin) is a disulfide-containing antibiotic and anti-angiogenic compound produced by Streptomyces. Thiolutin inhibits the JAMM metalloproteases Csn5, Associated-molecule-with-the-SH3-Domain-of-STAM (AMSH) and Brcc36[1]. Thiolutin is a potent and selective inhibitor of endothelial cell adhesion accompanied by rapid induction of Heat-shock protein beta-1 (Hsp27) phosphorylation[2].

[Related Catalog]:

Signaling Pathways >> Others >> Others

Research Areas >> Metabolic Disease

[References]

[1]. Lauinger L, et al. Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases. Nat Chem Biol. 2017 Jul;13(7):709-714.

[2]. Jia Y, et al. Thiolutin inhibits endothelial cell adhesion by perturbing Hsp27 interactions with components of the actin and intermediate filament cytoskeleton. Cell Stress Chaperones. 2010 Mar;15(2):165-81.

Chemical & Physical Properties

[ Density]:
1.6±0.1 g/cm3

[ Boiling Point ]:
478.6±45.0 °C at 760 mmHg

[ Melting Point ]:
273-276℃

[ Molecular Formula ]:
C₈H₈N₂O₂S₂

[ Molecular Weight ]:
228.291

[ Flash Point ]:
243.3±28.7 °C

[ Exact Mass ]:
228.002716

[ PSA ]:
107.58000

[ LogP ]:
0.99

[ Vapour Pressure ]:
0.0±1.2 mmHg at 25°C

[ Index of Refraction ]:
1.721

[ Water Solubility ]:
DMSO: 5 mg/mL

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: JP1355000

CHEMICAL NAME :: 1,2-Dithiolo(4.3-b)pyrrol-5(4H)-one, 6-acetamido-4-methyl-

CAS REGISTRY NUMBER :: 87-11-6

BEILSTEIN REFERENCE NO. :: 0209485

LAST UPDATED :: 199612

DATA ITEMS CITED :: 3

MOLECULAR FORMULA :: C8-H8-N2-O2-S2

MOLECULAR WEIGHT :: 228.30

WISWESSER LINE NOTATION :: T55 BNV FSSJ B1 DMV1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 25 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 25 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

MUTATION DATA

TYPE OF TEST :: Mutation test systems - not otherwise specified

TEST SYSTEM :: Yeast - Saccharomyces cerevisiae

DOSE/DURATION :: 4 mg/L

REFERENCE :: AMACCQ Antimicrobial Agents and Chemotherapy. (American Soc. for Microbiology, 1913 I St., NW, Washington, DC 20006) V.1- 1972- Volume(issue)/page/year: 3,729,1973

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H300

[ Precautionary Statements ]:
P264-P301 + P310

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ Hazard Codes ]:
T+: Very toxic;T: Toxic;

[ Risk Phrases ]:
28

[ Safety Phrases ]:
S45

[ RIDADR ]:
UN 2811 6.1/PG 2

[ WGK Germany ]:
3

[ RTECS ]:
JP1355000

[ HS Code ]:
2933990090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

Condensin targets and reduces unwound DNA structures associated with transcription in mitotic chromosome condensation.

Nat. Commun. 6 , 7815, (2015)

Chromosome condensation is a hallmark of mitosis in eukaryotes and is a prerequisite for faithful segregation of genetic material to daughter cells. Here we show that condensin, which is essential for...

Thiophene-degrading Escherichia coli mutants possess sulfone oxidase activity and show altered resistance to sulfur-containing antibiotics.

Appl. Environ. Microbiol. 56(10) , 3179-85, (1990)

We have previously isolated mutants of Escherichia coli which show increased oxidation of heterocyclic furan and thiophene substrates. We have now found that strains carrying the thdA mutation express...

Mapping of two transcription mutations (tlnI and tlnII) conferring thiolutin resistance, adjacent to dnaZ and rho in Escherichia coli.

Mol. Gen. Genet. 180(3) , 609-15, (1980)

Two mutations in Escherichia coli conferring resistance to the transcription initiation inhibitor, thiolutin, have been mapped. One of these mutations (tln-I)( maps at 10.2 min on the genetic map and ...