U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C60H90N6O14
Molecular Weight 1119.3907
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of EMODEPSIDE

SMILES

CC(C)C[C@@]1([H])C(=O)O[C@]([H])(C)C(=O)N(C)[C@@]([H])(CC(C)C)C(=O)O[C@]([H])(Cc2ccc(cc2)N3CCOCC3)C(=O)N(C)[C@@]([H])(CC(C)C)C(=O)O[C@]([H])(C)C(=O)N(C)[C@@]([H])(CC(C)C)C(=O)O[C@]([H])(Cc4ccc(cc4)N5CCOCC5)C(=O)N1C

InChI

InChIKey=ZMQMTKVVAMWKNY-YSXLEBCMSA-N
InChI=1S/C60H90N6O14/c1-37(2)31-47-57(71)77-41(9)53(67)61(11)50(34-40(7)8)60(74)80-52(36-44-17-21-46(22-18-44)66-25-29-76-30-26-66)56(70)64(14)48(32-38(3)4)58(72)78-42(10)54(68)62(12)49(33-39(5)6)59(73)79-51(55(69)63(47)13)35-43-15-19-45(20-16-43)65-23-27-75-28-24-65/h15-22,37-42,47-52H,23-36H2,1-14H3/t41-,42-,47+,48+,49+,50+,51-,52-/m1/s1

HIDE SMILES / InChI
Emodepside is a semi-synthetic product (originated by Astellas and out-licensed to Bayer for animal and human use); its precursor is synthesized by a fungus living in the leaves of Camellia japonica. It is a potent antihelminthic drug used in combination with praziquantel (as Profender®) and in combination with toltrazuril (as Procox®) for the treatment of parasitic worms in cats and dogs. Emodepside, a semi-synthetic derivative of PF1022A, belongs to a new class of anthelmintic drugs, the cyclooctadepsipeptides, and shows good efficacy against macrocyclic lactone-, levamisole- or benzimidazole-resistant nematode populations. Although putative receptors for emodepside have already been discovered, its mode of action is still not fully understood. It has being suggested that GABA(A)-receptor UNC-49 is associated with the emodepside mode of action. It has also being shown that Emodepside binds to a presynaptic latrophilin receptor in nematodes. The following presynaptic signal transduction occurs via activation of Gqalpha protein and phospholipase-Cbeta, which leads to mobilization of diacylglycerol (DAG). DAG then activates UNC-13 and synaptobrevin, two proteins which play an important role in presynaptic vesicle-functioning. This finally leads to the release of a currently unidentified transmitter. The transmitter (or modulator) exerts its effects at the postsynaptic membrane and induces a flaccid paralysis of the pharynx and the somatic musculature in nematodes.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: unc-49, Caenorhabditis elegans, UniProtKB - G5ECD3
Target ID: G5EDW2
Gene ID: 174419.0
Gene Symbol: lat-1
Target Organism: Caenorhabditis elegans
4.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
PROFENDER

Approved Use

PROFENDER Topical Solution is indicated for the treatment and control of hookworm infections caused by Ancylostoma tubaeforme (adults, immature adults, and fourth stage larvae), roundworm infections caused by Toxocara cati (adults and fourth stage larvae), and tapeworm infections caused by Dipylidium caninum (adults) and Taenia taeniaeformis (adults) in cats.

Launch Date

1.18307514E12
PubMed

PubMed

TitleDatePubMed
Cyclooctadepsipeptides--a new class of anthelmintically active compounds.
2002 Jun
The effect of the anthelmintic emodepside at the neuromuscular junction of the parasitic nematode Ascaris suum.
2003 Jan
Cyclooctadepsipeptides--an anthelmintically active class of compounds exhibiting a novel mode of action.
2003 Sep
Latrotoxin receptor signaling engages the UNC-13-dependent vesicle-priming pathway in C. elegans.
2004 Aug 10
Efficacy of two cyclooctadepsipeptides, PF1022A and emodepside, against anthelmintic-resistant nematodes in sheep and cattle.
2005 Mar
Effects of a combinations of emodepside and praziquantel on parasites of reptiles and rodents.
2005 Oct
Field evaluation of the efficacy and safety of emodepside/praziquantel spot-on solution against naturally acquired nematode and cestode infections in domestic cats.
2005 Oct
Efficacy of a topically administered combination of emodepside and praziquantel against mature and immature Ancylostoma tubaeforme in domestic cats.
2005 Oct
Evaluation of the efficacy of emodepside plus praziquantel topical solution against ascarid infections (Toxocara cati or Toxascaris leonina) in cats.
2005 Oct
Evaluation of the efficacy of emodepside+praziquantel topical solution against cestode (Dipylidium caninum, Taenia taeniaeformis, and Echinococcus multilocularis) infections in cats.
2005 Oct
Putative G protein-coupled receptors in parasitic nematodes--potential targets for the new anthelmintic class cyclooctadepsipeptides?
2005 Oct
Cyclohexadepsipeptides (CHDPs) with improved anthelmintical efficacy against the gastrointestinal nematode (Haemonchus contortus) in sheep.
2005 Oct
Influence of the cyclooctadepsipeptides PF1022A and PF1022E as natural products on the design of semi-synthetic anthelmintics such as emodepside.
2005 Oct
Mechanisms of action of emodepside.
2005 Oct
Insecticidal toxins from black widow spider venom.
2007 Mar 15
Effects of the novel anthelmintic emodepside on the locomotion, egg-laying behaviour and development of Caenorhabditis elegans.
2007 May
Developing novel anthelmintics from plant cysteine proteinases.
2008 Sep 1
FMRFamide-like neuropeptides as putative ligands of the latrophilin-like HC110-R from Haemonchus contortus.
2009 Apr
The putative cyclooctadepsipeptide receptor depsiphilin of the canine hookworm Ancylostoma caninum.
2009 Aug
Efficacy and safety of emodepside 2.1%/praziquantel 8.6% spot-on formulation in the treatment of feline aelurostrongylosis.
2009 Aug
Treatment and prevention of vertical transmission of Toxocara cati in cats with an emodepside/praziquantel spot-on formulation.
2009 Aug
Efficacy of emodepside plus praziquantel tablets (Profender tablets for dogs) against mature and immature cestode infections in dogs.
2009 Aug
Field evaluation of the efficacy and safety of emodepside plus praziquantel tablets (Profender tablets for dogs) against naturally acquired nematode and cestode infections in dogs.
2009 Aug
Efficacy of emodepside plus praziquantel tablets (Profender tablets for dogs) against mature and immature adult Trichuris vulpis infections in dogs.
2009 Aug
Efficacy of emodepside plus praziquantel tablets (Profender tablets for dogs) against mature and immature adult Ancylostoma caninum and Uncinaria stenocephala infections in dogs.
2009 Aug
Efficacy of emodepside plus praziquantel tablets (Profender tablets for dogs) against mature and immature infections with Toxocara canis and Toxascaris leonina in dogs.
2009 Aug
Onchocerciasis Control: Vision for the Future from a Ghanian perspective.
2009 Jan 21
Canine and feline cardiopulmonary parasitic nematodes in Europe: emerging and underestimated.
2010 Jul 23
A differential role for neuropeptides in acute and chronic adaptive responses to alcohol: behavioural and genetic analysis in Caenorhabditis elegans.
2010 May 3
Patents

Sample Use Guides

Each mL of Profender contains 21.4 mg emodepside and 85.7 mg praziquantel. Recommended minimum dosage is 1.36 mg/lb (3 mg/kg) emodepside and 5.45 mg/lb (12 mg/kg) praziquantel. Administer the entire contents of a unit applicator tube of PROFENDER Topical Solution topically one time.
Route of Administration: Topical
Emodepside was evaluated in a concentration range between 0.01 and 100 ug/ml against third-stage larvae (L3) and adult worms of Nippostrongylus brasiliensis and first-stage larvae (L1) of Trichinella spiralis. Emodepside had EC(50) value in the T. spiralis 0.02788 ug/ml and the N. brasiliensis 0.06188 ug/ml) motility assays.
Name Type Language
EMODEPSIDE
GREEN BOOK   INN   MI  
INN  
Official Name English
EMODEPSIDE [MI]
Common Name English
CYCLO((.ALPHA.R)-.ALPHA.-HYDROXY-4-(4-MORPHOLINYL)BENZENEPROPANOYL-N-METHYL-L-LEUCYL-(2R)-2-HYDROXYPROPANOYL-N-METHYL-L-LEUCYL-(.ALPHA.R)-.ALPHA.-HYDROXY-4-(4-MORPHOLINYL)BENZENEPROPANOYL-N-METHYL-L-LEUCYL-(2R)-2-HYDROXYPROPANOYL-N-METHYL-L-LEUCYL)
Common Name English
BAY-44-4400
Code English
EMODEPSIDE [GREEN BOOK]
Common Name English
PF 1022-221
Code English
PROCOX COMPONENT EMODEPSIDE
Brand Name English
BAY 44-4400
Code English
PF-1022-221
Code English
EMODEPSIDE COMPONENT OF PROCOX
Common Name English
PROFENDER COMPONENT EMODEPSIDE
Brand Name English
CYCLO((R)-LACTOYL-N-METHYL-L-LEUCYL-(R)-3-(P-MORPHOLINOPHENYL)LACTOYL-N-METHYL-L-LEUCYL-(R)-LACTOYL-N-METHYL-L-LEUCYL-(R)-3-(P-MORPHOLINOPHENYL)LACTOYL-N-METHYL-L-LEUCYL)
Common Name English
EMODEPSIDE [INN]
Common Name English
EMODEPSIDE COMPONENT OF PROFENDER
Brand Name English
EMODEPSIDE [EMA EPAR VETERINARY]
Common Name English
Classification Tree Code System Code
CFR 21 CFR 524.775
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
EMA VETERINARY ASSESSMENT REPORTS PROCOX [AUTHORIZED]
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
EMA VETERINARY ASSESSMENT REPORTS PROFENDER [AUTHORIZED]
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
WHO-VATC QP52AX60
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
FDA ORPHAN DRUG 535416
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
NCI_THESAURUS C250
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
EMA VETERINARY ASSESSMENT REPORTS PROFENDER [AUTHORIZED]
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
Code System Code Type Description
EPA CompTox
155030-63-0
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
PRIMARY
WIKIPEDIA
EMODEPSIDE
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
PRIMARY
ChEMBL
CHEMBL2104404
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
PRIMARY
DRUG BANK
DB11403
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
PRIMARY
INN
7893
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
PRIMARY
CAS
155030-63-0
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
PRIMARY
MESH
C468987
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
PRIMARY
FDA UNII
YZ647Y5GC9
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
PRIMARY
MERCK INDEX
M4887
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
PRIMARY Merck Index
NCI_THESAURUS
C90726
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
PRIMARY
RXCUI
354606
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
PRIMARY RxNorm
PUBCHEM
6918632
Created by admin on Fri Jun 25 22:42:41 UTC 2021 , Edited by admin on Fri Jun 25 22:42:41 UTC 2021
PRIMARY