Carcinogenicity testing in drug development: Getting it right

Baldrick, Paul; Jain, Sanjay

doi:10.1016/j.yrtph.2023.105522

Cited by 3 publications

(1 citation statement)

References 12 publications

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“…Carcinogenicity is a signi cant concern among the toxicological endpoints of drugs. Carcinogenic drugs can interfere with the genome or cellular metabolic processes in the human physiological system (Baldrick and Jain, 2023;Zenkov et al, 2020). Curcumin, Demethoxycurcumin, Bisdemethoxycurcumin, Cyclocurcumin were predicted to be non-carcinogenic (Table 5), attributable to their abilities to pass the in exible and thorough drug-likeness screening.…”

Section: Discussionmentioning

confidence: 99%

Identification and analysis of bioactive compounds in medicinal plants with potential therapeutic effects on Uterine fibroid using computational approaches

Fawibe,

Adekoya,

Oyelakin

et al. 2024

Preprint

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Uterine fibroids are gynaecological conditions in reproductive females, capable of growing in response to progesterone’s interaction with progesterone’s receptor protein (IA28). The use of surgery and hormone therapy for uterine fibroid treatment has limitations and side effects. Therefore, there is a need for an effective therapeutic approach to fibroid treatment. This study evaluated the inhibitory potential of phytocompounds present in some medicinal plants with anti-inflammatory properties (Vitex agnus castus, Curcuma longa, Allium sativum, Zingiber officinale, Trigonella foenum-graecum and Paeonia lactiflora) against IA28. Twenty-four (24) bioactive compounds were selected and screened while Ulipristal Acetate (UPA) was utilized as the control drug. The PubChem identification number and canonical SMILES of the phytocompounds and that of UPA were obtained using the PubChem online server. Drug-likeness screening and molecular docking analyses were carried out using web-based tools (SwissADME, AutoDock Vina, and Molinspiration). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles of the ligands were evaluated using ADMETlab. Out of the total phytocompounds, eleven passed the drug-likeness screening. However, only Casticin, Curcumin, Demethoxycurcumin, Bisdemethoxycurcumin, Cyclocurcumin, and Gingerol had higher binding energy of -7.6, -7.0, -7.5, -7.4, -8.0, and − 7.0 kcal/mol, respectively than the control drug (-6.7 kcal/mol) while Shogaol, and Gingerdiol had similar binding energy with the UPA. ADMET profiling predicted that the lead ligands with higher binding energy except Casticin and Gingerol were non-carcinogenic. Our study revealed that eleven phytocompounds had the potential to be used as antifibroid agents; however, six lead ligands were predicted to be more effective than the control drug.

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Section: Discussionmentioning

confidence: 99%

Identification and analysis of bioactive compounds in medicinal plants with potential therapeutic effects on Uterine fibroid using computational approaches

Fawibe,

Adekoya,

Oyelakin

et al. 2024

Preprint

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Studies on chlorophenyl, thiophenyl, and biphenyl clubbed tetrahydro bipyrazole carbaldehydes: Synthesis, antimicrobial and antioxidant activity, SAR study, in-silico pharmacokinetics, toxicity, and molecular modeling

Avika,

Kumar,

Yasin

et al. 2024

Chemical Physics Impact

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An industry perspective on the FDA Modernization Act 2.0/3.0: potential next steps for sponsors to reduce animal use in drug development

Carratt,

Zuch de Zafra,

Oziolor

et al. 2024

Toxicological Sciences

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Pharmaceutical developers are encouraged to adopt the best practices of being purposefully thoughtful about the use of animals, seeking alternatives wherever possible. They should engage with health authorities to increase their familiarity with the methods, study designs, data outputs and the context of use for new approach methodologies (NAMs). Although current state of technology does not yet provide adequate models to fully replace in vivo studies, many models are sufficiently good for an augmented approach that will enhance our understanding of in vitro to in vivo correlations and advance the long-term goal of reducing animal use through innovative NAMs. The goal of future nonclinical safety packages is to advance the utilization of such enabling technologies towards appropriate human risk characterization. Establishing confidence in NAMs is a critical first step. For example, sponsors may include both “traditional” and NAM-based nonclinical safety data in regulatory submissions to establish confidence with health authorities. In addition, regulators should create a “safe-harbor” for hybrid nonclinical data packages to facilitate iterative learning, refinement, and implementation of NAM-based safety assessment strategies. Sponsors are urged to contribute to NAMs evolution through consortia participation, peer-reviewed publications, and documenting animal reduction in studies/programs, accelerating the eventual elimination of animal use in pharmaceutical development, as envisioned in the FDA Modernization Act 3.0.

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Carcinogenicity testing in drug development: Getting it right

Cited by 3 publications

References 12 publications

Identification and analysis of bioactive compounds in medicinal plants with potential therapeutic effects on Uterine fibroid using computational approaches

Identification and analysis of bioactive compounds in medicinal plants with potential therapeutic effects on Uterine fibroid using computational approaches

Studies on chlorophenyl, thiophenyl, and biphenyl clubbed tetrahydro bipyrazole carbaldehydes: Synthesis, antimicrobial and antioxidant activity, SAR study, in-silico pharmacokinetics, toxicity, and molecular modeling

An industry perspective on the FDA Modernization Act 2.0/3.0: potential next steps for sponsors to reduce animal use in drug development

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