52665-74-4 Usage
Description
Manumycin A is an antibiotic derived from Streptomyces parvulus, characterized by its potent and selective farnesyltransferase (FTase) inhibitory properties. It plays a crucial role in preventing the activation of Ras proteins, which requires farnesylation for membrane attachment, and has demonstrated significant anti-tumor activity against Ki-ras-activated solid tumors. Additionally, Manumycin A has been shown to inhibit IκB kinase (IKK) independently of FTase inhibition, with effective concentrations ranging from 2-10 μM.
Uses
Used in Pharmaceutical Industry:
Manumycin A is used as an anti-tumor agent for its significant antitumor activity against Ki-ras-activated solid tumors in mice. It inhibits the activation of Ras proteins, which are often mutated in various cancers, thus providing a potential therapeutic approach for cancer treatment.
Used in Research Applications:
Manumycin A is used as an inhibitor of IκB kinase (IKK) and farnesyltransferase (FTase) in the homogeneous time-resolved fluorescence (HTRF)-based binding assay. This application aids in understanding the molecular interactions and signaling pathways involved in various cellular processes, including those related to cancer development and progression.
Used in Atherosclerosis Prevention and Treatment:
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. This finding indicates that FTase inhibition, achieved by Manumycin A, could be a potential target for the prevention or treatment of atherosclerosis, a condition characterized by the buildup of plaque in the arteries.
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
Check Digit Verification of cas no
The CAS Registry Mumber 52665-74-4 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,2,6,6 and 5 respectively; the second part has 2 digits, 7 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 52665-74:
(7*5)+(6*2)+(5*6)+(4*6)+(3*5)+(2*7)+(1*4)=134
134 % 10 = 4
So 52665-74-4 is a valid CAS Registry Number.
InChI:InChI=1/C31H38N2O7/c1-5-6-11-19(2)16-20(3)17-21(4)30(38)32-22-18-31(39,29-28(40-29)27(22)37)15-10-8-7-9-12-25(36)33-26-23(34)13-14-24(26)35/h7-10,12,15-19,28-29,34,39H,5-6,11,13-14H2,1-4H3,(H,32,38)(H,33,36)/b8-7+,12-9+,15-10+,20-16+,21-17+/t19-,28-,29-,31+/m1/s1
