gw844520 profile

GW844520: anti-malarial mitochondrial electron transport inhibitor; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ID Source	ID
PubMed CID	9887751
CHEMBL ID	467584
SCHEMBL ID	4472453
MeSH ID	M0507190

Synonym
3-chloro-2,6-dimethyl-5-[4-[4-(trifluoromethoxy)phenoxy]phenyl]-1h-pyridin-4-one
CHEMBL467584
gw844520
gw-844520
137735-25-2
gw 844520
4x9 ,
3-chloro-2,6-dimethyl-5-{4-[4-(trifluoromethoxy)phenoxy]phenyl}pyridin-4-ol
3-chloro-5-(4-(4-trifluoromethoxyphenoxy)phenyl)-2,6-dimethylpyridin-4(1h)-one
3-chloro-5-(4-(4-trifluoromethoxyphenoxy)phenyl)-2,6-dimethyl pyridin-4(1h)-one
SCHEMBL4472453
DTXSID20160296
Q27455192
AKOS040748510

Excerpt	Reference	Relevance
"GW844520 is a potent and selective inhibitor of the cytochrome bc1 complex of mitochondrial electron transport in P. "	( Preclinical drug metabolism and pharmacokinetic evaluation of GW844520, a novel anti-malarial mitochondrial electron transport inhibitor. Bambal, R; Davis, CB; Ferrer, S; Gargallo, D; Han, C; Hugger, E; McSurdy-Freed, J; Moorthy, GS; Xiang, H, 2006)	2.02

Excerpt	Reference	Relevance
" To evaluate full potential of this development candidate, we conducted drug metabolism and pharmacokinetic studies of this novel anti-malarial."	( Preclinical drug metabolism and pharmacokinetic evaluation of GW844520, a novel anti-malarial mitochondrial electron transport inhibitor. Bambal, R; Davis, CB; Ferrer, S; Gargallo, D; Han, C; Hugger, E; McSurdy-Freed, J; Moorthy, GS; Xiang, H, 2006)	0.57

Excerpt	Reference	Relevance
" Oral bioavailability was high (51-100%)."	( Preclinical drug metabolism and pharmacokinetic evaluation of GW844520, a novel anti-malarial mitochondrial electron transport inhibitor. Bambal, R; Davis, CB; Ferrer, S; Gargallo, D; Han, C; Hugger, E; McSurdy-Freed, J; Moorthy, GS; Xiang, H, 2006)	0.57
" In general, the most potent 4-pyridones are lipophilic molecules with poor solubility in aqueous media and low oral bioavailability in pre-clinical species from the solid dosage form."	( Potent antimalarial 4-pyridones with improved physico-chemical properties. Bueno, JM; Chicharro, J; Ferrer, S; Fiandor, JM; Fraile, MT; García, A; García, MC; Gargallo-Viola, D; Gómez, RM; Herreros, E; Lavandera, JL; Lorenzo, M; Manzano, P; Puente, M; Vidal, J, 2011)	0.37
" Selected as a preclinical candidate, ELQ-300 has good oral bioavailability at efficacious doses in mice, is metabolically stable, and is highly active in blocking transmission in rodent models of malaria."	( Quinolone-3-diarylethers: a new class of antimalarial drug. Angulo-Barturen, I; Avery, VM; Bathurst, I; Burrows, JN; Charman, SA; Cross, RM; Delves, MJ; Duffy, S; Ferrer, S; Forquer, IP; Gamo, FJ; Guy, RK; Herreros, E; Jiménez-Díaz, MB; Kelly, JX; Kocken, CHM; Kyle, DE; LaCrue, AN; Li, Y; Manetsch, R; Marfurt, J; Mather, MW; Morrisey, JM; Mutka, T; Nilsen, A; Noviyanti, R; Price, RN; Riscoe, MK; Ryan, E; Saenz, FE; Sanz, LM; Sebayang, BF; Shackleford, DM; Siegl, P; Sinden, RE; Steuten, J; Vaidya, AB; White, KL; Winter, RW; Wirjanata, G; Zeeman, AM, 2013)	0.39

Excerpt	Relevance	Reference
" In general, the most potent 4-pyridones are lipophilic molecules with poor solubility in aqueous media and low oral bioavailability in pre-clinical species from the solid dosage form."	( Potent antimalarial 4-pyridones with improved physico-chemical properties. Bueno, JM; Chicharro, J; Ferrer, S; Fiandor, JM; Fraile, MT; García, A; García, MC; Gargallo-Viola, D; Gómez, RM; Herreros, E; Lavandera, JL; Lorenzo, M; Manzano, P; Puente, M; Vidal, J, 2011)	0.37

Bioassays (34)

Assay ID	Title	Year	Journal	Article
AID617168	Chromatographic hydrophobicity index of the compound at pH 7.4 by rapid gradient HPLC analysis	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617179	Volume of distribution in CD1 mouse at 0.2 mg/kg, iv	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617186	Half life in Beagle dog at 0.05 mg/kg, iv	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID384959	Antimalarial activity as reduced parasitaemia against Plasmodium yoelii YM in CD1 mice (Mus musculus) given a single peroral dose	2008	Journal of medicinal chemistry, May-08, Volume: 51, Issue:9	Synthesis and structure-activity relationships of 4-pyridones as potential antimalarials.
AID384958	Antimalarial activity as reduced parasitaemia against Plasmodium yoelii YM in CD1 mice (Mus musculus) after 7 peroral doses over 4 days	2008	Journal of medicinal chemistry, May-08, Volume: 51, Issue:9	Synthesis and structure-activity relationships of 4-pyridones as potential antimalarials.
AID384960	Antimalarial activity against Plasmodium falciparum 3D7A infected erythrocytes by [3H]hypoxanthine uptake	2008	Journal of medicinal chemistry, May-08, Volume: 51, Issue:9	Synthesis and structure-activity relationships of 4-pyridones as potential antimalarials.
AID1733042	Antimalarial activity against ring stage artemisinin-sensitive Plasmodium falciparum F32-TEM assessed as time taken for recrudescence by measuring parasitemia at 7 uM after 48 hrs	2021	Bioorganic & medicinal chemistry letters, 05-01, Volume: 39	Novel molecule combinations and corresponding hybrids targeting artemisinin-resistant Plasmodium falciparum parasites.
AID617184	Volume of distribution in Beagle dog at 0.05 mg/kg, iv	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617176	Solubility of the compound in PBS at pH 7.4	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID384957	Antimalarial activity against Plasmodium falciparum T9-96 infected Rhesus positive human erythrocytes by [3H]hypoxanthine uptake	2008	Journal of medicinal chemistry, May-08, Volume: 51, Issue:9	Synthesis and structure-activity relationships of 4-pyridones as potential antimalarials.
AID617181	Half life in CD1 mouse at 0.2 mg/kg, iv	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617173	Solubility of the compound in simulated gastric fluid at pH 1.2	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID1733048	Antimalarial activity against Plasmodium falciparum assessed as difference of time taken for recrudescence Plasmodium falciparum F32 ART1 between ring stage artemisinin-sensitive Plasmodium falciparum F32-TEM measured at 7 uM after 48 hrs	2021	Bioorganic & medicinal chemistry letters, 05-01, Volume: 39	Novel molecule combinations and corresponding hybrids targeting artemisinin-resistant Plasmodium falciparum parasites.
AID617183	Oral bioavailability in Beagle dog at 2 mg/kg	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID420345	Antimalarial activity after 48 hrs against Plasmodium falciparum T9-96 by [3H]hypoxanthine uptake	2009	Bioorganic & medicinal chemistry letters, Jul-01, Volume: 19, Issue:13	Design, synthesis and structure-activity relationships of (1H-pyridin-4-ylidene)amines as potential antimalarials.
AID617180	Clearance in CD1 mouse at 0.2 mg/kg, iv	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617166	Antimalarial activity against Plasmodium falciparum infected in A-positive human erythrocytes assessed as [3H]-hypoxanthine uptake after 24 hrs by liquid scintillation counter	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617172	Intrinsic solubility of the neutral form of compound	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617167	Chromatographic hydrophobicity index of the compound at pH 2 by rapid gradient HPLC analysis	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID1733036	Selective index, ratio of CC50 for African green monkey Vero cells to IC50 for plasmodium falciparum	2021	Bioorganic & medicinal chemistry letters, 05-01, Volume: 39	Novel molecule combinations and corresponding hybrids targeting artemisinin-resistant Plasmodium falciparum parasites.
AID384962	Antimalarial activity as parasite elimination against Plasmodium falciparum infected Aotus monkeys at 10 mg/kg/day for 7 days	2008	Journal of medicinal chemistry, May-08, Volume: 51, Issue:9	Synthesis and structure-activity relationships of 4-pyridones as potential antimalarials.
AID617174	Solubility of the compound in fed state simulated intestinal fluid at pH 5.0	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617175	Solubility of the compound in fasted state simulated intestinal fluid at pH 6.8	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617171	Dissociation constant, pKa of the compound	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617185	Clearance in Beagle dog at 0.05 mg/kg, iv	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617170	Partition coefficient, log P of the compound	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID1733034	Antimalarial activity against artemisinin-sensitive Plasmodium falciparum F32-TEM by SYBR green dye based fluorescence assay	2021	Bioorganic & medicinal chemistry letters, 05-01, Volume: 39	Novel molecule combinations and corresponding hybrids targeting artemisinin-resistant Plasmodium falciparum parasites.
AID617178	Oral bioavailability in CD1 mouse at 10 mg/kg	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID1733038	Antimalarial activity against ring stage artemisinin-resistant Plasmodium falciparum F32-ART5 assessed as time taken for recrudescence by measuring parasitemia at 7 uM after 48 hrs	2021	Bioorganic & medicinal chemistry letters, 05-01, Volume: 39	Novel molecule combinations and corresponding hybrids targeting artemisinin-resistant Plasmodium falciparum parasites.
AID384961	Antimalarial activity against Plasmodium falciparum FCR3-A infected erythrocytes as [3H]hypoxanthine incorporation	2008	Journal of medicinal chemistry, May-08, Volume: 51, Issue:9	Synthesis and structure-activity relationships of 4-pyridones as potential antimalarials.
AID617182	Cmax in Beagle dog at 2 mg/kg, po	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617169	Chromatographic hydrophobicity index of the compound at pH 10.5 by rapid gradient HPLC analysis	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID1733035	Cytotoxicity against African green monkey Vero cells assessed as inhibition of cell proliferation	2021	Bioorganic & medicinal chemistry letters, 05-01, Volume: 39	Novel molecule combinations and corresponding hybrids targeting artemisinin-resistant Plasmodium falciparum parasites.
AID617177	Cmax in CD1 mouse at 10 mg/kg, po	2011	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18	Potent antimalarial 4-pyridones with improved physico-chemical properties.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	3 (50.00)	29.6817
2010's	2 (33.33)	24.3611
2020's	1 (16.67)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	0 (0.00%)	5.53%
Reviews	0 (0.00%)	6.00%
Case Studies	0 (0.00%)	4.05%
Observational	0 (0.00%)	0.25%
Other	6 (100.00%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Classes	Roles
chloroquine Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.. chloroquine : An aminoquinoline that is quinoline which is substituted at position 4 by a [5-(diethylamino)pentan-2-yl]amino group at at position 7 by chlorine. It is used for the treatment of malaria, hepatic amoebiasis, lupus erythematosus, light-sensitive skin eruptions, and rheumatoid arthritis.	2.77	3	aminoquinoline; organochlorine compound; secondary amino compound; tertiary amino compound	anticoronaviral agent; antimalarial; antirheumatic drug; autophagy inhibitor; dermatologic drug
triclosan [no description available]	2.31	1	aromatic ether; dichlorobenzene; monochlorobenzenes; phenols	antibacterial agent; antimalarial; drug allergen; EC 1.3.1.9 [enoyl-[acyl-carrier-protein] reductase (NADH)] inhibitor; EC 1.5.1.3 (dihydrofolate reductase) inhibitor; fungicide; persistent organic pollutant; xenobiotic
carbostyril Quinolones: A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.. quinolin-2(1H)-one : A quinolone that is 1,2-dihydroquinoline substituted by an oxo group at position 2.	2.08	1	monohydroxyquinoline; quinolone	bacterial xenobiotic metabolite
clopidol pharmcoccide: Russian drug; no other info available 1/1/79	2.45	2	chloropyridine
mefloquine (-)-(11S,2'R)-erythro-mefloquine : An optically active form of [2,8-bis(trifluoromethyl)quinolin-4-yl]-(2-piperidyl)methanol having (-)-(11S,2'R)-erythro-configuration. An antimalarial agent, used in racemic form, which acts as a blood schizonticide; its mechanism of action is unknown.	2.31	1	[2,8-bis(trifluoromethyl)quinolin-4-yl]-(2-piperidyl)methanol	antimalarial
chloroquine diphosphate [no description available]	2.04	1
artemisinin (+)-artemisinin : A sesquiterpene lactone obtained from sweet wormwood, Artemisia annua, which is used as an antimalarial for the treatment of multi-drug resistant strains of falciparum malaria.	2.31	1	organic peroxide; sesquiterpene lactone	antimalarial; plant metabolite
atovaquone Atovaquone: A hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols.. atovaquone : A naphthoquinone compound having a 4-(4-chlorophenyl)cyclohexyl group at the 2-position and a hydroxy substituent at the 3-position.	3	4	hydroxy-1,2-naphthoquinone
proguanil Proguanil: A biguanide compound which metabolizes in the body to form cycloguanil, an anti-malaria agent.. proguanil : A biguanide compound which has isopropyl and p-chlorophenyl substituents on the terminal N atoms. A prophylactic antimalarial drug, it works by inhibiting the enzyme dihydrofolate reductase, which is involved in the reproduction of the malaria parasites Plasmodium falciparum and P. vivax within the red blood cells.	2.08	1	biguanides; monochlorobenzenes	antimalarial; antiprotozoal drug; EC 1.5.1.3 (dihydrofolate reductase) inhibitor

Condition	Relationship Strength	Studies
Infections, Plasmodium [description not available]	2.46	2
Malaria A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.	2.46	2
Plasmodium falciparum Malaria [description not available]	2.55	2
Malaria, Falciparum Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.	2.55	2

gw844520

Description

Cross-References

Synonyms (14)

Research Excerpts

Overview

Pharmacokinetics

Bioavailability

Dosage Studied

Bioassays (34)

Research

Studies (6)

Study Types

gw844520

Description

Cross-References

Synonyms (14)

Research Excerpts

Overview

Pharmacokinetics

Bioavailability

Dosage Studied

Bioassays (34)

Research

Studies (6)

Study Types

Related Drugs (9)

Related Conditions (4)