Current drug discovery technologies ·3 Nov 2026 ·Added 11 Nov 2026

Phytocannabinoids: Promising New Candidates for TYRP1 Protein Inhibition in Melanoma.

Ikram Ghicha, Sanae Baghrous, Fatiha Bousselham, Youness Kadil, Hasnaa Bazhar, Imane Rahmoune, Houda Filali

DOI ↗

Abstract

INTRODUCTION/OBJECTIVE: Phytocannabinoids, cannabinoids that occur naturally in cannabis, have gained significant attention due to their potential therapeutic benefits in managing diseases, including cancer. Tyrosinase-related protein 1 (TYRP1) plays an important role in melanogenesis and has been implicated in melanoma. This study was conducted to investigate the inhibitory potential of selected phytocannabinoids against TYRP1 and to identify these compounds as potential drugs for managing melanoma. METHODS: An in silico study was conducted, and molecular docking was performed to assess the binding affinity between phytocannabinoids and TYRP1. Pharmacokinetics was conducted using ADMET analysis, while toxicity was predicted using ProTox-II. In addition, molecular dynamics simulations were performed using GROMACS to evaluate the stability of the protein-ligand complex. RESULTS: The study showed that cannabichromene (CBC) has high binding affinity for this target. This was confirmed by molecular docking, which revealed stable interactions between the protein's active site and the ligand. In addition, a molecular dynamics simulation was performed, and the results confirmed that the protein-ligand complex remained stable throughout the simulation period. ADMET analysis showed that CBC has good intestinal absorption and moderate transdermal permeability. Furthermore, ProTox-II results showed that CBC has low toxicity. DISCUSSION: The results demonstrate the potential of phytocannabinoids, especially CBC, as inhibitors of TYRP1. The high binding affinity and molecular stability suggest that CBC may have TYRP1 inhibitory activity. The TYRP1 interference may be responsible for its effects on melanogenesis and melanoma progression. Additionally, its pharmacokinetic profile and low toxicity make CBC a promising phytocannabinoid for its intended application. CONCLUSION: This study has identified cannabichromene as a promising phytocannabinoid with potential inhibitory activity against TYRP1. This has provided a basis for experimental validation to prove its therapeutic potential in melanoma and pigment disorders.