In silico Prediction of Skin Sensitization: Quo vadis?

Abstract

Skin direct contact with chemical or physical substances is predisposed to allergic contact dermatitis (ACD), producing various allergic reactions, namely rash, blister, or itchy, in the contacted skin area. ACD can be triggered by various extremely complicated adverse outcome pathways (AOPs) remains to be causal for biosafety warrant. As such, commercial products such as ointments or cosmetics can fulfill the topically safe requirements in animal and non-animal models including allergy. Europe, nevertheless, has banned animal tests for the safety evaluations of cosmetic ingredients since 2013, followed by other countries. A variety of non-animal in vitro tests addressing different key events of the AOP, the direct peptide reactivity assay (DPRA), KeratinoSens™, LuSens and human cell line activation test h-CLAT and U-SENS™ have been developed and were adopted in OECD test guideline to identify the skin sensitizers. Other methods, such as the SENS-IS are not yet fully validated and regulatorily accepted. A broad spectrum of in silico models, alternatively, to predict skin sensitization have emerged based on various animal and non-animal data using assorted modeling schemes. In this article, we extensively summarize a number of skin sensitization predictive models that can be used in the biopharmaceutics and cosmeceuticals industries as well as their future perspectives, and the underlined challenges are also discussed.

Chemoinformatic Design and Profiling of Derivatives of Dasabuvir, Efavirenz, and Tipranavir as Potential Inhibitors of Zika Virus RNA-Dependent RNA Polymerase and Methyltransferase

“…This suggests that the compounds will not cause allergic reactions such as rash, blisters, or itch when in contact with the skin. 68 Few of the designed compounds ( 12 ) with better binding energies are noninhibitors of human ether-a-go-go-related genes I and II (hERG I and hERG II) ( Tables 5 and 6 ). The rest of the designed compounds are inhibitors of hERG II but not hERG I ( Tables 2 and 4 – 6 ).…”

“…No skin sensitization was observed in the designed derivatives of dasabuvir, efavirenz, and tipranavir (Tables and–). This suggests that the compounds will not cause allergic reactions such as rash, blisters, or itch when in contact with the skin . Few of the designed compounds ( 12 ) with better binding energies are noninhibitors of human ether-a-go-go-related genes I and II (hERG I and hERG II) (Tables and ).…”

In Silico Prediction and Insights Into the Structural Basis of Drug Induced Nephrotoxicity

“…The model building was performed on the online chemical database and modeling environment (OCHEM), which is a user friendly web-based platform for automatic and simple QSAR modeling ( Sushko et al, 2011 ). OCHEM supports the typical steps of QSAR modeling, and the models can be published and publicly used on the web ( Oprisiu et al, 2013 ; Cui et al, 2019 ; Pawar et al, 2019 ; Cui et al, 2021 ; Hua et al, 2021 ; Huang et al, 2021 ; Ta et al, 2021 ). Among the many state-of-the-art modeling methods available on OCHEM, we applied five widely used traditional machine learning (ML) approaches and five different deep learning (DL) algorithms.…”

In Silico Prediction of Skin Permeability Using a Two-QSAR Approach

“…The skin, which is the largest organ in human body [ 1 ] due to the fact that it has the largest surface and accounts ca. 15% of adult body weight [ 2 ], provides a major barrier against the external environment from the internal environment [ 3 ]. It is composed of multiple layers, namely the surface epidermis, the deeper dermis, and the innermost subcutis [ 4 ], which, in turn, have different constructs, morphology forms, and functions [ 5 ].…”