Last update 01 Nov 2024

Melanin x TYR

Last update 01 Nov 2024

Basic Info

Related Targets

MelaninTYR

Drugs associated with Melanin x TYR

AP-736

Target

Melanin x TYR

Mechanism

Melanin inhibitors [+1]

Active Org.

Amorepacific Corp.

Originator Org.

Amorepacific Corp.

Active Indication-

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Melanin x TYR

100 Translational Medicine associated with Melanin x TYR

0 Patents (Medical) associated with Melanin x TYR

789

Literatures (Medical) associated with Melanin x TYR

11 Dec 2024·Journal of Biomolecular Structure and Dynamics

Design, synthesis, in silico ADME, DFT, molecular dynamics simulation, anti-tyrosinase, and antioxidant activity of some of the 3-hydroxypyridin-4-one hybrids in combination with acylhydrazone derivatives

Article

Author: Sadeghpour, Hossein ; Jokar Darzi, Habibollah ; Khoshneviszadeh, Mehdi ; Hassani, Bahareh ; Fazel, Razieh ; Zare, Fateme ; Poustforoosh, Alireza ; Sabet, Razieh ; Behrouz, Marzieh

Tyrosinase is the rate-limiting enzyme in synthesizing melanin. Melanin is responsible for changing the color of fruits and vegetables and protecting against skin photo-carcinogenesis. Herein, some of the hybrids of 3-hydroxypyridine-4-one and acylhydrazones were designed and synthesized to study the anti-tyrosinase and antioxidant activities. The diphenolase activity of mushroom tyrosinase using L-DOPA assayed the inhibitory effects, and the antioxidant activity was assessed using DPPH free radical. The synthesized derivatives were confirmed using ¹H-NMR, ¹³C-NMR, IR, and Mass spectroscopy. Among analogs, compound 5h bearing furan ring with IC₅₀=8.94 μM was more potent than kojic acid (IC₅₀=16.68 μM). The pharmacokinetic profile of the compounds showed that the tested compounds had suitable oral bioavailability and drug-likeness properties. The molecular docking studies showed that compound 5h was located in the tyrosinase-binding site. Also, the molecular dynamics simulation was performed on compound 5h, proving the obtained molecular docking results. At the B3LYP/6-31 + G** level of theory, the reactivity descriptors for 5 g and 5h were investigated using DFT calculations. Also, IR frequency was calculated to verify DFT results with experimental data. The electrostatic potential energy of the surface and the HOMO and LUMO molecular orbitals were also studied. It agrees with experimental results that the 5h is a soft molecule and ready for chemical reaction with other interacting molecules.Communicated by Ramaswamy H. Sarma.

01 Nov 2024·Bioorganic Chemistry

Melanin resistance of heat-processed ginsenosides from Panax ginseng berry treated with citric acid through autophagy pathway

Article

Author: Han, Linlin ; Ren, Honghong ; Li, Xiaomin ; Zhao, Wenjie ; Zhao, Yuqing ; He, Xiaojing ; Li, Mingkun ; Tan, Hongyan ; Chai, Jiayi ; Lee, Jungjoon ; Liu, Shiyu

GFRS is the conversion product of Panax ginseng Meyer berry after citric acid heat treatment, which is rich in rare ginsenosides. However, the anti-melanin role of GFRS in the regulation of skin pigmentation and its material basis remains unclear. To compare the anti-melanin activity before and after citric acid heat treatment, we determined the effects of GFS and GFRS on tyrosinase activity and melanin lever under α-MSH stimulation and found the potential anti-melanin effect of GFRS. Further, Western blot and immunofluorescence methods were used to reveal the mechanism by which GFRS detects anti-melanin activity by promoting autophagy flux levels. In zebrafish models, GFRS inhibited endogenous melanin and tyrosinase better than arbutin and promoted the accumulation of autophagy levels in vivo. To determine the material basis of the anti-melanin effect of GFRS, HPLC was used to isolate and prepare 12 ginsenosides from GFRS, and their activity evaluation and structure-activity relationship analysis were performed. The results showed that the inhibitory effect of GFRS on melanin was Rg₃ > Rg₅ > Rk₁ > Rd. Molecular docking showed that their docking fraction with mushroom tyrosinase was significantly better than that of arbutin, but the presence of C-20 glycosylation decreased the anti-melanin activity of Rd. To maximize the content of Rg₃, Rg₅, and Rk₁, we optimized the process by using citric acid heat treatment of ginsenoside Rd and found that citric acid heat treatment at 100°C almost completely transformed Rd and obtained a high content of active ingredients. In summary, our data demonstrated that GFRS exerted anti-melanin effects by inducing autophagy. It was further revealed that Rg₃, Rg₅, and Rk₁, as effective active components, could be enriched by the improved process of converting ginsenoside Rd by citric acid heat treatment.

02 Oct 2024·Current Topics in Medicinal Chemistry

Identification of Novel Tyrosinase Inhibitors with Nanomolar Potency Using Virtual Screening Approaches

Article

Author: Liu, Shihao ; Liu, Guohong ; Wang, Tegexibaiyin ; Li, Xiaofang

Introduction:Hyperpigmentation disorders are caused by excess production of the pigment melanin, catalyzed by the enzyme tyrosinase. Novel tyrosinase inhibitors are needed as therapeutic agents to treat these conditions.Method:To discover new inhibitors, we performed a virtual screening of the ZINC20 library containing 1.4 billion compounds. An initial filter for drug-likeness, ADMET properties, and synthetic accessibility reduced the library to 10,217 hits. Quantitative structure-activity relationship (QSAR) modeling of this subset predicted nanomolar inhibitory potency for several chemical scaffolds. Comparative molecular docking studies and rigorous binding energy calculations further prioritized four cysteine-containing dipeptide compounds based on predicted strong binding affinity and mode to tyrosinase.Results:Microsecond-long molecular dynamics simulations provided additional atomistic insights into the stability of inhibitor-enzyme binding interactions. This integrated computational workflow effectively sampled an extremely large chemical space to discover four novel tyrosinase inhibitors with half-maximal inhibitory concentration values below 10 nM.Conclusion:Overall, this demonstrates the power of virtual screening and multi-faceted computational techniques to accelerate the discovery of potent bioactive ligands from massive compound libraries by efficiently sampling chemical space.

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