Lotamilast

SKU: orb1223546

Description

Lotamilast (RVT 501, E6005) is a potent, selective PDE4 inhibitor with IC50 of 2.8 nM, suppresses the production of various cytokines from human lymphocytes and monocytes with IC50 of 0.49-3.1 nM; produces an immediate antipruritic effect as well as an anti-inflammatory effect with reduced expression of cytokines/adhesion molecules in mice after topical application; ameliorates the appearance of atopic dermatitis-like skin lesions in AD models.Dermatitis Phase 2 Clinical(In Vitro):Lotamilast potently and selectively inhibits human PDE4 activity with an IC50 of 2.8 nM and suppresses the production of various cytokines from human lymphocytes and monocytes with IC50 values ranging from 0.49 to 3.1 nM.(In Vivo):Lotamilast is currently in phase 2 development for patients with mild-to-moderate atopic dermatitis. In mice models, the topical application of Lotamilast produces an immediate antipruritic effect as well as an anti-inflammatory effect with reduced expression of cytokines/adhesion molecules. On the basis of these observed effects, topical RVT-501 ameliorates the appearance of atopic dermatitis-like skin lesions in two types of AD models, hapten- and mite-elicited models, exhibiting inhibitory effects comparable to that of tacrolimus. A single topical application of Lotamilast significantly inhibits spontaneous scratching during 1–2 h after application in mice with chronic dermatitis; the inhibition is partial and similar between 0.01% and 0.03%. Topical application of 0.03% Lotamilast to the rostral back significantly inhibits the increased activity of the cutaneous nerve in mice with chronic dermatitis. The cutaneous concentration of cAMP is significantly decreased in mice with chronic dermatitis, and this decrease is reversed by topical Lotamilast application.

Key Properties

• CAS Number: 947620-48-6
• MW: 472.501
• Purity: >98% (HPLC)
• Formula: C₂₆H₂₄N₄O₅
• SMILES: O=C(OC)C1=CC=C(C(NC2=CC=CC(C3=C4C=C(OC)C(OC)=CC4=NC(NC)=N3)=C2)=O)C=C1
• Target: PDE
• Solubility: < 1 mg/ml refers to the product slightly soluble or insoluble

Bioactivity

• In Vivo:
  Lotamilast is currently in phase 2 development for patients with mild-to-moderate atopic dermatitis. In mice models, the topical application of Lotamilast produces an immediate antipruritic effect as well as an anti-inflammatory effect with reduced expression of cytokines/adhesion molecules. On the basis of these observed effects, topical RVT-501 ameliorates the appearance of atopic dermatitis-like skin lesions in two types of AD models, hapten-and mite-elicited models, exhibiting inhibitory effects comparable to that of tacrolimus. A single topical application of Lotamilast significantly inhibits spontaneous scratching during 1–2 h after application in mice with chronic dermatitis; the inhibition is partial and similar between 0.01% and 0.03%. Topical application of 0.03% Lotamilast to the rostral back significantly inhibits the increased activity of the cutaneous nerve in mice with chronic dermatitis. The cutaneous concentration of cAMP is significantly decreased in mice with chronic dermatitis, and this decrease is reversed by topical Lotamilast application.
• In Vitro:
  Lotamilast potently and selectively inhibits human PDE4 activity with an IC50 of 2.8 nM and suppresses the production of various cytokines from human lymphocytes and monocytes with IC50 values ranging from 0.49 to 3.1 nM.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

RVT 501 | E6005

Quick Database Links

Gene Symbol

PDE