MANUMYCIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C31H38N2O7
Molecular Weight	550.6426
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	5
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCC[C@@H](C)\C=C(C)\C=C(/C)C(=O)NC1=C[C@@](O)(\C=C\C=C\C=C\C(=O)NC2=C(O)CCC2=O)[C@@H]3O[C@@H]3C1=O

InChI

InChIKey=TWWQHCKLTXDWBD-MVTGTTCWSA-N

InChI=1S/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

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8460134 | https://www.ncbi.nlm.nih.gov/pubmed/27307747 | https://www.ncbi.nlm.nih.gov/pubmed/27176604 | https://www.ncbi.nlm.nih.gov/pubmed/26352011

Manumycin is a natural product isolated from Streptomyces parvulus. It has been reported to have anti-carcinogenic and anti-biotic properties. It acts as a potent and selective farnesyltransferase inhibitor. Manumycin inhibited PI3K-AKT activation and led to ROS accumulation and caspase-9 activation in the colorectal cancer cells. Manumycin induces apoptosis in malignant pleural mesothelioma through regulation of Sp1 and activation of the mitochondria-related apoptotic pathway. It is a potential to treat human oral squamous cell carcinoma via cell apoptosis through the downregulation of Sp1.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
PI3K-Akt signaling pathway 25 Target ID: map04151 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27307747	Inhibitor 8504
Protein farnesyltransferase 13 Target ID: CHEMBL2095197 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8460134	Inhibitor 8504	1.2 µM [Ki]
Apoptosis 156 Target ID: WP254 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26352011	Activator 1447

Conditions

Condition	Modality	Highest Phase	Product
Colorectal cancer 102 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27307747	Primary	Basic research	Unknown Approved Use Unknown
Fibrosarcoma 4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8460134	Primary	Preclinical	Unknown Approved Use Unknown
Oral squamous cell carcinoma 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26352011	Primary	Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Areca nut components affect COX-2, cyclin B1/cdc25C and keratin expression, PGE2 production in keratinocyte is related to reactive oxygen species, CYP1A1, Src, EGFR and Ras signaling.	2014	25051199
Signaling cascades mediate astrocyte death induced by zinc.	2011-07-28	21575692
Involvement of H-Ras and reactive oxygen species in proinflammatory cytokine-induced matrix metalloproteinase-13 expression in human articular chondrocytes.	2011-03-15	21211511
Selective cytotoxicity of glycyrrhetinic acid against tumorigenic r/m HM-SFME-1 cells: potential involvement of H-Ras downregulation.	2010-02-15	19958823
Farnesyltransferase inhibitors reduce Ras activation and ameliorate acetaminophen-induced liver injury in mice.	2009-11	19739265
Manumycin inhibits STAT3, telomerase activity, and growth of glioma cells by elevating intracellular reactive oxygen species generation.	2009-08-15	19409983
Receptor-mediated tobacco toxicity: acceleration of sequential expression of alpha5 and alpha7 nicotinic receptor subunits in oral keratinocytes exposed to cigarette smoke.	2008-05	18450646
Expression of rTSbeta as a 5-fluorouracil resistance marker in patients with primary breast cancer.	2008-04	18357371
Simvastatin alleviates diabetes-induced VEGF-mediated nephropathy via the modulation of Ras signaling pathway.	2008	18569938
Methylglyoxal-induced fibronectin gene expression through Ras-mediated NADPH oxidase activation in renal mesangial cells.	2007-08	17635749
Ras modulation of superoxide activates ERK-dependent fibronectin expression in diabetes-induced renal injuries.	2006-05	16572112

Patents

Sample Use Guides

In Vivo Use Guide

Mice: 6.3 mg/kg daily for 5 days

Route of Administration: Intraperitoneal

In Vitro Use Guide

Manumycin inhibited the cell viability of MSTO-211H and H28 cells in a concentration‑dependent manner as determined by MTS assay. IC50 values were calculated as 8.3 and 4.3 uM in the MSTO-311H and H28 cells following 48 h incubation, respectively.

Name

Type

Language

MANUMYCIN

Common Name

English

NSC-622141

Preferred Name

English

2,4-DECADIENAMIDE, N-(5-HYDROXY-5-(7-((2-HYDROXY-5-OXO-1- CYCLOPENTEN-1-YL)AMINO)-7-OXO-1,3,5-HEPTATRIENYL)-2-OXO-7- OXABICYCLO(4.1.0)HEPT-3-EN-3-YL)-2,4,6-TRIMETHYL-

Systematic Name

English

MANUMYCIN A

Common Name

English

UCF-1C

Code

English

(-)-MANUMYCIN A

Common Name

English

2,4-DECADIENAMIDE, N-((1S,5S,6R)-5-HYDROXY-5-((1E,3E,5E)-7-((2-HYDROXY-5-OXO-1-CYCLOPENTEN-1-YL)AMINO)-7-OXO-1,3,5-HEPTATRIEN-1-YL)-2-OXO-7-OXABICYCLO(4.1.0)HEPT-3-EN-3-YL)-2,4,6-TRIMETHYL-, (2E,4E,6R)-

Systematic Name

English

Code System Code Type Description

PUBCHEM

6438330