Disease Information

General Information of the Disease (ID: DIS00304)

• Name: Asthma
• ICD: ICD-11: CA23

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Brinzolamide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Interleukin-1 beta (IL1B) [1]

• Resistant Disease: Asthma [ICD-11: CA23.0]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Brinzolamide
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549/NF-kappaB-luc reporter cells; Lung; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: NF-kappaB activity assay
• Mechanism Description: Corticosteroid resistance causes significant morbidity in asthma, and drug repurposing may identify timely and cost-effective adjunctive treatments for corticosteroid resistance. gamma-linolenic acid, brinzolamide, and INCA-6 significantly reduced IL-1beta induced luciferase activity and potentiated the anti-inflammatory effect of dexamethasone in A549/NF-kappaB-luc reporter cells. These results demonstrate how existing drugs, including gamma-linolenic acid, brinzolamide, and INCA-6, may be repurposed to improve corticosteroid response in asthmatics.

Dicyclomine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Cholinergic receptor muscarinic 1 (CHRM1) [2]

• Sensitive Disease: Asthma [ICD-11: CA23.0]
• Molecule Alteration: Function; Inhibition
• Sensitive Drug: Dicyclomine
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Guinea-pig model; Cavia cutleri
• Experiment for Molecule Alteration: cAMP estimation analysis
• Mechanism Description: Dicyclomine, an antagonist of muscarinic receptors as well as an inhibitor of Ca++ ion influx, exhibited a similar pattern of inhibition with lower EC50 values against CCh when compared with high K+. In isolated guinea pig trachea, TS Oil inhibited carbachol (CCh, 1 M) and K+ (80 mM)-induced contractions in a pattern similar to that of dicyclomine. Methicillin-resistant S. aureus (MRSA) showed a small zone of inhibition as compared to standard strains (22 mm).

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Plasma membrane calcium-transporting ATPase 1 (ATP2B1) [2]

• Sensitive Disease: Asthma [ICD-11: CA23.0]
• Molecule Alteration: Function; Inhibition
• Sensitive Drug: Dicyclomine
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Guinea-pig model; Cavia cutleri
• Experiment for Molecule Alteration: cAMP estimation analysis
• Mechanism Description: Dicyclomine, an antagonist of muscarinic receptors as well as an inhibitor of Ca++ ion influx, exhibited a similar pattern of inhibition with lower EC50 values against CCh when compared with high K+. In isolated guinea pig trachea, TS Oil inhibited carbachol (CCh, 1 M) and K+ (80 mM)-induced contractions in a pattern similar to that of dicyclomine. Methicillin-resistant S. aureus (MRSA) showed a small zone of inhibition as compared to standard strains (22 mm).

References

• Ref 1: Drug Repurposing to Treat Glucocorticoid Resistance in Asthma .J Pers Med. 2021 Mar 3;11(3):175. doi: 10.3390/jpm11030175. 10.3390/jpm11030175
• Ref 2: Possible Tracheal Relaxant and Antimicrobial Effects of the Essential Oil of Ethiopian Thyme Species (Thymus serrulatus Hochst. ex Benth.): A Multiple Mechanistic Approach .Front Pharmacol. 2021 Apr 5;12:615228. doi: 10.3389/fphar.2021.615228. eCollection 2021. 10.3389/fphar.2021.615228