MANUMYCIN A Property

Boiling point:

863.6±65.0 °C(Predicted)

Density 

1.26±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

Soluble in DMSO (up to 10 mg/ml), in Ethanol (up to 5 mg/ml) or in DMF (up to 20 mg/ml)

form 

Yellow to brown solid

pka

3.80±0.30(Predicted)

color 

Yellow

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO, ethanol, or DMF may be stored at -20°C for up to 3 months.

Safety

WGK Germany 

3

HS Code 

2941900000

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H319Causes serious eye irritation

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P321Specific treatment (see … on this label).

P330Rinse mouth.

P337+P313IF eye irritation persists: Get medical advice/attention.

P501Dispose of contents/container to..…

MANUMYCIN A Chemical Properties,Usage,Production

Description

Manumycin A is an antibiotic that acts as a potent and selective farnesyltransferase (FTase) inhibitor with anti-tumor activity. It inhibits rat brain FTase with a K_i value of 1.2 μM, thereby preventing Ras activation which requires farnesylation at the C-terminus for membrane attachment. It exhibits significant antitumor activity against K_i-ras-activated solid tumors in mice at a dose of 6.3 mg/kg. Manymycin A inhibits IκB kinase (IKK), independent of FTase inhibition, in an number of cells types with effective concentrations of 2-10 μM. In ApoE-deficient mice, Manumycin A treatment for 22 weeks at 5 mg/kg reduced aortic fatty streak lesion size to 43% of vehicle-treated animals, indicating FTase inhibition as a potential target for prevention or treatment of atherosclerosis.

Uses

Manumycin A from Streptomyces parvulus has been used to inhibit IκB kinase (IKK)b?nuclear κ-B essential modulator (NEMO) interaction in the homogeneous time-resolved fluorescence (HTRF)-based binding assay.

Uses

Manumycin A is an antibiotic that acts as a potent and selective farnesyltransferase (FTase) inhibitor with anti-tumor activity.

Definition

ChEBI: Manumycin A is a polyketide with formula C31H38N2O7 initially isolated from Streptomyces parvulus as a result of a random screening program for farnesyl transferase (FTase) inhibitors. It is a natural product that exhibits anticancer and antibiotic properties. It has a role as an EC 1.8.1.9 (thioredoxin reductase) inhibitor, an EC 2.5.1.58 (protein farnesyltransferase) inhibitor, an antineoplastic agent, an apoptosis inducer, an antimicrobial agent, a bacterial metabolite, an antiatherosclerotic agent and a marine metabolite. It is a polyketide, an enamide, an epoxide, an organic heterobicyclic compound, a secondary carboxamide and a tertiary alcohol.

Biochem/physiol Actions

Manumycin A is a natural monomeric epoxyquinoid. It has an ability to inhibit tumor necrosis factor (TNF) induced IκB kinase (IKK) activity in various cell types. In addition, manumycin A exhibits anti-tumor property by inhibiting farnesylation of oncogenic Ras.

References

1) Hara?et al.?(1993),?Identification of Ras Farnesyltransferase inhibitors by microbial screening; Proc. Natl. Acad. Sci. USA,?90?2281 2) DiPaolo?et al.?(2000),?Manumycin inhibits ras signal transduction pathway and induces apoptosis in COLO320-DM human colon tumour cells; Br. J. Cancer,?82?905 3) Arenz?et al.?(2001),?Manumycin A and its analogies are irreversible inhibitors of neutral sphingomyelinase; Chem. Bio. Chem.,?2?141 4) Sharma?et al.?(2012),?Farnesyltransferase inhibitor manumycin targets IL1β-Ras-HIF-1α axis in tumor cells of diverse origin; Inflammation,?35?516 5) Saha and Nandi (2009),?Farnesyltransferase inhibitors reduce Ras activation and ameliorate acetaminophen-induced liver injury in mice; Hepatology,?50?1547 6) Singha?et al.?(2013),?Manumycin A inhibits triple-negative breast cancer growth through LC3-mediated cytoplasmic vacuolation death; Cell Death Dis.,?4?e457