Drug Information

Drug (ID: DG02162) and It's Reported Resistant Information

• Name: IRAK-1 and -4 dual inhibitor
• Synonyms: IRAK-1 and -4 dual inhibitor
• Indication:
  In total 1 Indication(s)
  . .; .; [1]

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Laryngeal cancer [ICD-11: 2C23]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Interleukin-1 receptor-associated kinase 1 (IRAK1) [1]

• Sensitive Disease: Laryngeal carcinoma [ICD-11: 2C23.2]
• Molecule Alteration: Phosphorylation; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: IRAK-1 and-4 signaling pathway; Regulation; N.A.
• In Vitro Model: HEp-2 cells; Skin; Homo sapiens (Human); CVCL_1906
• Experiment for Molecule Alteration: Gene expression profiling assay; Flow cytometry; Western blot assay; ELISA assay
• Experiment for Drug Resistance: Drug sensitivity assay
• Mechanism Description: In this study, we investigated the role of Interleukin-1 receptor-associated kinases (IRAK) mediated Toll-like receptor (TLR)-signaling in chemo-resistance using a cell line-based in-vitro TPF-resistant HNSCC model of laryngeal origin. TPF chemo-resistant state showed over-expression and phosphorylation of the active downstream kinases IRAK-1 and IRAK-4 along with enhanced proliferative potential, survival, stemness and metastatic capability as compared to the parent cell line. Pharmacological inhibition of IRAK-1 and -4 had a cytostatic effect on chemo-resistant cells and re-sensitized them to chemotherapy. The treatment also decreased the pro-oncogenic effects of the chemo-resistant cells. Our study provides insights into the pro-oncogenic role of amplified IRAK-1 and-4 mediated TLR signaling in TPF-resistant HNSCC. Pharmacological inhibition of IRAK-1 and-4 signaling is a promising therapeutic strategy for TPF-resistant HNSCC. It can also be used as a combination therapy or a chemo-drug sparing regimen in HNSCC.

References

• Ref 1: Suppression of TLR signaling by IRAK-1 and -4 dual inhibitor decreases TPF-resistance-induced pro-oncogenic effects in HNSCC. 3 Biotech. 2023 Jan;13(1):14.