ARTEFENOMEL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C28H39NO5
Molecular Weight	469.613
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C(CN1CCOCC1)OC2=CC=C(C=C2)[C@H]3CC[C@@]4(CC3)OO[C@@]5(O4)C6CC7CC(C6)CC5C7

InChI

InChIKey=XLCNVWUKICLURR-WMORPJFDSA-N

InChI=1S/C28H39NO5/c1-3-26(31-14-11-29-9-12-30-13-10-29)4-2-22(1)23-5-7-27(8-6-23)32-28(34-33-27)24-16-20-15-21(18-24)19-25(28)17-20/h1-4,20-21,23-25H,5-19H2/t20?,21?,23-,24?,25?,27-,28-

HIDE SMILES / InChI

Description
Sources: https://www.mmv.org/related-story-type/artefenomel | https://www.ncbi.nlm.nih.gov/pubmed/21300861 |

Artefenomel, a novel trioxolane, is a lead candidate for inclusion in a new antimalarial combination, specifically formulated for children. Artefenomel has been demonstrated curative in as little as one dose.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
gametophyte development 2 Target ID: GO:0048229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25667405 \| https://www.ncbi.nlm.nih.gov/pubmed/28052200	Interacts 323

Conditions

Condition	Modality	Targets	Highest Phase	Product
Plasmodium falciparum malaria 63 Sources: https://clinicaltrials.gov/ct2/show/NCT02083380	Curative		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
1710 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26448141	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	ARTEFENOMEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1500 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26448141	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	ARTEFENOMEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
339 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26448141	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	ARTEFENOMEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
732 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26448141	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ARTEFENOMEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
19700 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26448141	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	ARTEFENOMEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
25100 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26448141	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	ARTEFENOMEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3180 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26448141	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	ARTEFENOMEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6450 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26448141	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ARTEFENOMEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
58 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26448141	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	ARTEFENOMEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
57 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26448141	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	ARTEFENOMEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
46.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26448141	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	ARTEFENOMEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
62.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26448141	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ARTEFENOMEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 CYP2C19 1478 CYP2B6 810 CYP1A2 1524	CYP3A4/5 85

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34101429/	no
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34101429/	no
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34101429/	no
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34101429/	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34101429/	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34101429/	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34101429/	yes [IC50 9.8 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4/5 85	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/34101429/	major

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34101	https://www.001chemical.com/chem/search?q=DY34101
Chem Scene	CS-0012378	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0012378
MedChem Express	HY-16762	https://www.medchemexpress.com/search.html?q=HY-16762&ft=&fa=&fp=
MolPort	MolPort-046-788-446	https://www.molport.com/shop/molecule-link/MolPort-046-788-446
Molcore	MC34101	http://www.molcore.com/CatMC34101.html
Molnova	M10144	https://www.molnova.com/en/serch-list.html?keywords=M10144
MuseChem	I002862	https://www.musechem.com/product/I002862.html
eMolecules	194971605	https://orderbb.emolecules.com/search/#?query=194971605

PubMed

Title	Date	PubMed
Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria.	2011 Mar 15	21300861
Single dose treatment of malaria - current status and perspectives.	2016 Jul	27254098
Efficacy of OZ439 (artefenomel) against early Plasmodium falciparum blood-stage malaria infection in healthy volunteers.	2016 Sep	27272721

Patents

Sample Use Guides

In Vivo Use Guide

In clinical trials, Artefenomel is administered in 800 mg doses in loose combination with Piperaquine phosphate doses of either 640, 960, 1440 mg

Route of Administration: Oral

In Vitro Use Guide

Asexual parasites were seeded at a density of 0.5% parasitemia in 3% hematocrit in a black 384-well plate in 30 μL of culture medium, and 30 μL of diluted compound was added. Following a 72 h incubation at 37°C, 98% humidity, 93% N2, 4% CO2 and 3% O2, the increase in parasitemia was assessed using the modified Plasmodium lactate dehydrogenase assay. Artefenomel was diluted in DMSO and subsequently in culture medium to reach a final DMSO concentration of 0.1%.

Name

Type

Language

ARTEFENOMEL

Official Name

English

MORPHOLINE, 4-(2-(4-CIS-DISPIRO(CYCLOHEXANE-1,3'-(1,2,4)TRIOXOLANE-5',2''-TRICYCLO(3.3.1.13,7)DECAN)-4-YLPHENOXY)ETHYL)-

Systematic Name

English

OZ439

Code

English

4-(2-(4-(CIS-DISPIRO(ADAMANTANE-2,3'-(1,2,4)TRIOXOLANE-5',1''-CYCLOHEXANE)-4''-YL)PHENOXY)ETHYL)MORPHOLINE

Systematic Name

English

OZ-439

Code

English

artefenomel [INN]

Common Name

English

CIS-ADAMANTANE-2-SPIRO-3'-8'-(4'-(2'-(4'-MORPHOLINYL)ETHOXY)PHENYL)-1',2,'4'-TRIOXASPIRO(4.5)DECANE

Common Name

English

Artefenomel [WHO-DD]

Common Name

English

Code System Code Type Description

EVMPD

SUB181577