Ramoplanin

Identification

Name
Ramoplanin
Accession Number
DB04952
Type
Small Molecule
Groups
Investigational
Description

Ramoplanin is a novel glycolipodepsipeptide antibiotic under development for the treatment of CDAD.

Structure
Thumb
Synonyms
Not Available
Categories
UNII
0WX9996O2G
CAS number
76168-82-6
Weight
Average: 2554.066
Monoisotopic: 2552.03504662
Chemical Formula
C119H154ClN21O40
InChI Key
KGZHFKDNSAEOJX-GVRPVQITSA-N
InChI
InChI=1S/C119H154ClN21O40/c1-54(2)17-11-9-14-22-82(153)127-77(50-81(123)152)107(166)141-93-99(101(124)160)180-117(176)92(66-33-44-78(151)72(120)49-66)140-102(161)56(5)126-105(164)75(47-55(3)4)128-83(154)51-125-108(167)87(61-23-34-67(147)35-24-61)136-111(170)86(59(8)146)134-113(172)89(65-31-42-71(43-32-65)177-119-100(97(158)95(156)80(53-143)179-119)181-118-98(159)96(157)94(155)79(52-142)178-118)135-104(163)73(20-15-45-121)129-106(165)76(48-60-18-12-10-13-19-60)131-109(168)84(57(6)144)133-114(173)90(63-27-38-69(149)39-28-63)138-115(174)91(64-29-40-70(150)41-30-64)137-110(169)85(58(7)145)132-103(162)74(21-16-46-122)130-112(171)88(139-116(93)175)62-25-36-68(148)37-26-62/h9-14,18-19,22-44,49,54-59,73-77,79-80,84-100,118-119,142-151,155-159H,15-17,20-21,45-48,50-53,121-122H2,1-8H3,(H2,123,152)(H2,124,160)(H,125,167)(H,126,164)(H,127,153)(H,128,154)(H,129,165)(H,130,171)(H,131,168)(H,132,162)(H,133,173)(H,134,172)(H,135,163)(H,136,170)(H,137,169)(H,138,174)(H,139,175)(H,140,161)(H,141,166)/b11-9-,22-14-/t56-,57-,58+,59+,73+,74+,75-,76+,77+,79+,80+,84-,85+,86+,87-,88+,89-,90+,91+,92+,93-,94+,95+,96-,97-,98-,99+,100-,118+,119+/m0/s1
IUPAC Name
(2R)-N-[(3R,6S,9S,15S,18R,21S,24R,27R,30S,33R,36R,39R,42R,45R,48S,49R)-24,42-bis(3-aminopropyl)-27-benzyl-49-carbamoyl-3-(3-chloro-4-hydroxyphenyl)-21-(4-{[(2S,3S,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-{[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}oxan-2-yl]oxy}phenyl)-18,39-bis[(1R)-1-hydroxyethyl]-30-[(1S)-1-hydroxyethyl]-15,33,36,45-tetrakis(4-hydroxyphenyl)-6-methyl-9-(2-methylpropyl)-2,5,8,11,14,17,20,23,26,29,32,35,38,41,44,47-hexadecaoxo-1-oxa-4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-pentadecaazacyclononatetracontan-48-yl]-2-[(2Z,4Z)-7-methylocta-2,4-dienamido]butanediamide
SMILES
NCCC[C@H]1NC(=O)[C@@H](CC2=CC=CC=C2)NC(=O)[C@H]([C@@H](O)C)NC(=O)[C@H](NC(=O)[C@H](NC(=O)[C@@H]([C@@H](C)O)NC(=O)[C@@H](CCCN)NC(=O)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](CC(N)=O)NC(=O)\C=C/C=C\CC(C)C)[C@@H](OC(=O)[C@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H]([C@@H](C)O)NC(=O)[C@@H](NC1=O)C1=CC=C(C=C1)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O)C1=CC=C(O)C=C1)C1=CC(Cl)=C(O)C=C1)C(N)=O)C1=CC=C(O)C=C1)C1=CC=C(O)C=C1)C1=CC=C(O)C=C1

Pharmacology

Indication

For the treatment of bacterial infections.

Pharmacodynamics

Ramoplanin represents a new class of antibiotics with a novel mechanism of action that is highly effective against Staphylococci.

Mechanism of action

Ramoplanin is the first in a new class of antimicrobials to reach clinical trials. It is a glycolipodepsipeptide produced by the fermentation of Actinoplanes spp.. Ramoplanin blocks bacterial cell wall biosynthesis by interfering with peptidoglycan production. Ramoplanin inhibits the N-acetylglucosaminyltransferase-catalysed conversion of lipid intermediate I to lipid intermediate II, a step that occurs before the transglycosylation and transpeptidation reactions. Ramoplanin’s mechanism of action is distinct from that of glycopeptides. Unlike glycopeptides, ramoplanin does not complex with the D-Ala–D-Ala sequence of cell wall precursors.

Absorption

No/limited absorption.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Gram-positive Bacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Ramoplanin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Ramoplanin is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Ramoplanin is combined with 4-hydroxycoumarin.
AcenocoumarolThe risk or severity of bleeding can be increased when Ramoplanin is combined with Acenocoumarol.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Ramoplanin.
Anthrax immune globulin humanThe therapeutic efficacy of Anthrax immune globulin human can be decreased when used in combination with Ramoplanin.
Anthrax vaccineThe therapeutic efficacy of Anthrax vaccine can be decreased when used in combination with Ramoplanin.
Bacillus calmette-guerin substrain connaught live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain connaught live antigen can be decreased when used in combination with Ramoplanin.
Bacillus calmette-guerin substrain danish 1331 live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain danish 1331 live antigen can be decreased when used in combination with Ramoplanin.
Bacillus calmette-guerin substrain tice live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain tice live antigen can be decreased when used in combination with Ramoplanin.
Food Interactions
Not Available

References

General References
  1. Fang X, Tiyanont K, Zhang Y, Wanner J, Boger D, Walker S: The mechanism of action of ramoplanin and enduracidin. Mol Biosyst. 2006 Jan;2(1):69-76. Epub 2005 Nov 29. [PubMed:16880924]
  2. Fulco P, Wenzel RP: Ramoplanin: a topical lipoglycodepsipeptide antibacterial agent. Expert Rev Anti Infect Ther. 2006 Dec;4(6):939-45. [PubMed:17181409]
External Links
PubChem Compound
73425378
PubChem Substance
175426916
ChemSpider
32813311
Wikipedia
Ramoplanin

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0503 mg/mLALOGPS
logP1.7ALOGPS
logP-9ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)7.85ChemAxon
pKa (Strongest Basic)10.28ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count41ChemAxon
Hydrogen Donor Count36ChemAxon
Polar Surface Area999.59 Å2ChemAxon
Rotatable Bond Count35ChemAxon
Refractivity632.19 m3·mol-1ChemAxon
Polarizability255.35 Å3ChemAxon
Number of Rings10ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.5625
Blood Brain Barrier-0.985
Caco-2 permeable-0.6849
P-glycoprotein substrateSubstrate0.8136
P-glycoprotein inhibitor INon-inhibitor0.698
P-glycoprotein inhibitor IINon-inhibitor0.865
Renal organic cation transporterNon-inhibitor0.9317
CYP450 2C9 substrateNon-substrate0.8407
CYP450 2D6 substrateNon-substrate0.8261
CYP450 3A4 substrateSubstrate0.6122
CYP450 1A2 substrateNon-inhibitor0.8729
CYP450 2C9 inhibitorNon-inhibitor0.8015
CYP450 2D6 inhibitorNon-inhibitor0.8713
CYP450 2C19 inhibitorNon-inhibitor0.722
CYP450 3A4 inhibitorNon-inhibitor0.5083
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7878
Ames testNon AMES toxic0.6914
CarcinogenicityNon-carcinogens0.8517
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5615 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9872
hERG inhibition (predictor II)Non-inhibitor0.5913
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as cyclic glycodepsipeptides. These are peptidomimetic containing a glycodepisipeptide backbone that lies in a cyclic moiety.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Peptidomimetics
Sub Class
Depsipeptides
Direct Parent
Cyclic glycodepsipeptides
Alternative Parents
Phenolic glycosides / Asparagine and derivatives / Macrolide lactams / Alpha amino acid esters / Macrolactams / Macrolides and analogues / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Disaccharides / O-glycosyl compounds
show 26 more
Substituents
Cyclic glycodepsipeptide / Phenolic glycoside / Macrolide lactam / Asparagine or derivatives / Macrolactam / Macrolide / N-acyl-alpha amino acid or derivatives / Alpha-amino acid ester / Alpha-amino acid amide / O-glycosyl compound
show 51 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Drug created on October 21, 2007 16:23 / Updated on November 02, 2018 06:07