LOTAMILAST

Details

Stereochemistry	ACHIRAL
Molecular Formula	C26H24N4O5
Molecular Weight	472.4926
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC1=NC2=C(C=C(OC)C(OC)=C2)C(=N1)C3=CC=CC(NC(=O)C4=CC=C(C=C4)C(=O)OC)=C3

InChI

InChIKey=BBTFKAOFCSOZMB-UHFFFAOYSA-N

InChI=1S/C26H24N4O5/c1-27-26-29-20-14-22(34-3)21(33-2)13-19(20)23(30-26)17-6-5-7-18(12-17)28-24(31)15-8-10-16(11-9-15)25(32)35-4/h5-14H,1-4H3,(H,28,31)(H,27,29,30)

HIDE SMILES / InChI

Molecular Formula	C26H24N4O5
Molecular Weight	472.4926
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23674603 | https://www.ncbi.nlm.nih.gov/pubmed/24645735 | https://www.ncbi.nlm.nih.gov/pubmed/26581111 | https://www.ncbi.nlm.nih.gov/pubmed/30265585

E-6005 is a novel PDE4 inhibitor developed as a topical agent for atopic dermatitis (AD). It potently and selectively inhibited human PDE4 activity and suppressed the production of various cytokines from human lymphocytes and monocytes. In mice models, the topical application of E6005 produced an immediate antipruritic effect as well as an anti-inflammatory effect with reduced expression of cytokines/adhesion molecules. E-6005 increases the cutaneous concentration of cAMP to relieve dermatitis-associated itching. E-6005 may be a promising novel therapeutic agent with antipruritic activity for the treatment of AD. E-6005 is currently in phase 2 development for patients with mild-to-moderate atopic dermatitis.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Phosphodiesterase 4 52 Target ID: CHEMBL2093863 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23674603	Inhibitor 8297		2.8 nM [IC50]

PubMed

Title	Date	PubMed
Antipruritic effect of the topical phosphodiesterase 4 inhibitor E6005 ameliorates skin lesions in a mouse atopic dermatitis model.	2013 Jul	23674603
Topical E6005, a novel phosphodiesterase 4 inhibitor, attenuates spontaneous itch-related responses in mice with chronic atopy-like dermatitis.	2014 May	24645735
An inhaled phosphodiesterase 4 inhibitor E6005 suppresses pulmonary inflammation in mice.	2015 Dec 5	26455478
Safety, tolerability and pharmacokinetics of a novel phosphodiesterase inhibitor, E6005 ointment, in healthy volunteers and in patients with atopic dermatitis.	2016	26581111
Effect of topical phosphodiesterase 4 inhibitor E6005 on Japanese children with atopic dermatitis: Results from a randomized, vehicle-controlled exploratory trial.	2016 Aug	26703371
Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: An investigator-blinded, vehicle-controlled study.	2016 Oct	27080209
Topical E6005/RVT-501, a novel phosphodiesterase 4 inhibitor, for the treatment of atopic dermatitis.	2017 Dec	29068253
A dried blood spot assay with UPLC-MS/MS for the simultaneous determination of E6005, a phosphodiesterase 4 inhibitor, and its metabolite in human blood.	2018 Aug 5	29803912
Pharmacokinetic disposition of topical phosphodiesterase-4 inhibitor E6005 in patients with atopic dermatitis.	2019 Aug	30265585

Patents

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:21:39 GMT 2023` Edited by `admin` on `Sat Dec 16 08:21:39 GMT 2023`
Record UNII	TO043KKB9C
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LOTAMILAST

Official Name

English

(METHYL 4-(((3-(6,7-DIMETHOXY-2-(METHYLAMINO)QUINAZOLIN-4-YL)PHENYL(AMINO)CARBONYL)BENZOATE

Common Name

English

E6005

Code

English

RVT-501

Code

English

BENZOIC ACID, 4-(((3-(6,7-DIMETHOXY-2-(METHYLAMINO)-4-QUINAZOLINYL)PHENYL)AMINO)CARBONYL)-, METHYL ESTER

Systematic Name

English

E-6005

Common Name

English

lotamilast [INN]

Common Name

English

LOTAMILAST [USAN]

Common Name

English

Lotamilast [WHO-DD]

Common Name

English

Code System Code Type Description

USAN

DE-133