Drug Information

Drug (ID: DG02169) and It's Reported Resistant Information

• Name: CMU-0101
• Synonyms: CMU-0101
• 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

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Protein kinase C delta type (PRKCD) [1]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: NF-kB signaling pathway; Activation; hsa04218
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: The sotrastaurin derivative CMU-0101 exhibited an elevated affinity for binding to the ATP-binding site of PKCdelta and effectively suppressed nuclear PKCdelta in resistant cells in comparison to sotrastaurin. Protein kinase C (PKC) is a family of serine/threonine kinases that play important roles in signal transduction, cell proliferation, differentiation, and apoptosis. In lung cancers, the nuclear localization of PKC delta (nPKCdelta) has emerged as a common resistant mediator across various known TKI-resistant pathways. nPKCdelta is actively expressed in a significant portion of TKI-resistant patients and is associated with poor survival in EGFR-mutant patients treated with TKIs. The nPKCdelta-mediated pathway, including AKT and NF-kB, has been implicated in promoting resistance to EGFR inhibitors by activating alternative survival signaling pathways that bypass the blocked EGFR signaling and bolster tumor growth.

References

• Ref 1: Development of triazole-based PKC-inhibitors to overcome resistance to EGFR inhibitors in EGFR-mutant lung cancers. Am J Cancer Res. 2023 Oct 15;13(10):4693-4707. eCollection 2023.