MK-0359 BESYLATE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C31H29N3O5S2.C6H6O3S
Molecular Weight	745.884
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OS(=O)(=O)C1=CC=CC=C1.CC2=NOC(=N2)C(=C\C3=CC(=CC=C3)C4=CC(=CC5=C4N=CC=C5)C(C)(C)S(C)(=O)=O)\C6=CC=C(C=C6)S(C)(=O)=O

InChI

InChIKey=AJIOTCZAAOYCQD-HYEBSWNJSA-N

InChI=1S/C31H29N3O5S2.C6H6O3S/c1-20-33-30(39-34-20)28(22-11-13-26(14-12-22)40(4,35)36)17-21-8-6-9-23(16-21)27-19-25(31(2,3)41(5,37)38)18-24-10-7-15-32-29(24)27;7-10(8,9)6-4-2-1-3-5-6/h6-19H,1-5H3;1-5H,(H,7,8,9)/b28-17+;

HIDE SMILES / InChI

Molecular Formula	C6H6O3S
Molecular Weight	158.175
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C31H29N3O5S2
Molecular Weight	587.709
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17428447 | https://www.ncbi.nlm.nih.gov/pubmed/19135348

MK-0359 (L-454560) is a selective and potent type 4 phosphodiesterases (PDE4) inhibitor, which binds to both the apo-(Mg2+-free) and holoenzyme states of PDE4. This compound successfully has passed the phase II clinical trial for the treatment of asthma, Pulmonary Disease, Chronic Obstructive (COPD) and Rheumatoid Arthritis. However, there is no information about the further research of this drug.

Approval Year

Targets

Primary Target	Pharmacology	Potency
cAMP-specific 3',5'-cyclic phosphodiesterase 4A 3 Target ID: P27815\|\|\|Q8WUQ3 Gene ID: 5141.0 Gene Symbol: PDE4A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17428447	Inhibitor 8504	1.6 nM [IC50]
cAMP-specific 3',5'-cyclic phosphodiesterase 4B 6 Target ID: Q07343 Gene ID: 5142.0 Gene Symbol: PDE4B Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17428447	Inhibitor 8504	0.5 nM [IC50]
cAMP-specific 3',5'-cyclic phosphodiesterase 4D 3 Target ID: Q08499\|\|\|Q8IVD2 Gene ID: 5144.0 Gene Symbol: PDE4D Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17428447	Inhibitor 8504	1.2 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Asthma 244 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19135348	Primary	Phase II 1147	Unknown Approved Use Unknown
Rheumatoid arthritis 320 Sources: https://clinicaltrials.gov/ct2/show/NCT00482417	Palliative	Phase II 1147	Unknown Approved Use Unknown
Pulmonary disease, chronic obstructive 3 Sources: https://clinicaltrials.gov/ct2/show/NCT00482235	Primary	Phase II 1147	Unknown Approved Use Unknown

AUC

Value	Dose	Co-administered	Analyte	Population
3367 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19135348	15 mg 1 times / day multiple, oral dose: 15 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MK-0359 blood	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
Axon MedChem	1127	https://www.axonmedchem.com/product/1127
eMolecules	36366932	https://orderbb.emolecules.com/search/#?query=36366932
eMolecules	44848313	https://orderbb.emolecules.com/search/#?query=44848313
Lan Pharmatech	LQT-B45143
MolPort	MolPort-042-665-643	https://www.molport.com/shop/molecule-link/MolPort-042-665-643
MuseChem	I008006	https://www.musechem.com/product/I008006.html
Norris Pharm	NSZB-A242665

PubMed

Title	Date	PubMed
In silico pharmacology suggests ginger extracts may reduce stroke risks.	2011-09	21776525
Alkyl-bridged substituted 8-arylquinolines as highly potent PDE IV inhibitors.	2009-09-01	19640717
Randomized, placebo-controlled study of a selective PDE4 inhibitor in the treatment of asthma.	2009-03	19135348
L-454,560, a potent and selective PDE4 inhibitor with in vivo efficacy in animal models of asthma and cognition.	2007-06-15	17428447

Sample Use Guides

In Vivo Use Guide

MK-0359 (15mg/day) or placebo for 14 days, then crossed-over to the other treatment for 14 days

Route of Administration: Oral

In Vitro Use Guide

L-454,560 (MK-0359) is a potent, competitive and preferential inhibitor of PDE4A, 4B, and 4D with IC50 values of 1.6, 0.5 and 1.2 nM, respectively. L-454,560 binds to both the apo-(Mg2+-free) and holoenzyme states of PDE4. The intrinsic enzyme potency for PDE4 inhibition by L-454,560 also results in an effective blockade of LPS-induced TNFalpha formation in whole blood (IC50 = 161 nM) and is comparable to the human whole blood potency of roflumilast. The cytokine profile of inhibition of L-454,560 is mainly a Th1 profile with significant inhibition of IFNgamma and no detectable inhibition of IL-13 formation up to 1 microM.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:12:02 GMT 2025` Edited by `admin` on `Mon Mar 31 18:12:02 GMT 2025`
Record UNII	I5H8YF7WYQ
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

L-454560 BESILATE

Preferred Name

English

MK-0359 BESYLATE

Code

English

QUINOLINE, 6-(1-METHYL-1-(METHYLSULFONYL)ETHYL)-8-(3-((1E)-2-(3-METHYL-1,2,4-OXADIAZOL-5-YL)-2-(4-(METHYLSULFONYL)PHENYL)ETHENYL)PHENYL)-, BENZENESULFONATE (1:1)

Systematic Name

English

MK-0359 BESILATE

Code

English

L-454560 BESYLATE

Code

English

Code System Code Type Description

PUBCHEM

9853497

Created by admin on Mon Mar 31 18:12:02 GMT 2025 , Edited by admin on Mon Mar 31 18:12:02 GMT 2025

PRIMARY

EPA CompTox

DTXSID80721802

Created by admin on Mon Mar 31 18:12:02 GMT 2025 , Edited by admin on Mon Mar 31 18:12:02 GMT 2025

PRIMARY

FDA UNII

I5H8YF7WYQ

Created by admin on Mon Mar 31 18:12:02 GMT 2025 , Edited by admin on Mon Mar 31 18:12:02 GMT 2025

PRIMARY

CAS

346630-09-9

Created by admin on Mon Mar 31 18:12:02 GMT 2025 , Edited by admin on Mon Mar 31 18:12:02 GMT 2025

PRIMARY

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Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/17428447 | https://www.ncbi.nlm.nih.gov/pubmed/19135348

Approval Year

Targets

Conditions

Approved Use

Approved Use

Approved Use

AUC

Sourcing

PubMed

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17428447 | https://www.ncbi.nlm.nih.gov/pubmed/19135348