Toxicity Prediction Studies Research Articles

Machine learning in paediatric haematological malignancies: a systematic review of prognosis, toxicity and treatment response models.

Machine Learning (ML) has demonstrated potential in enhancing care in adult oncology. However, its application in paediatric haematological malignancies is still emerging, necessitating a comprehensive review of its capabilities and limitations in this area. A literature search was conducted through Ovid. Studies included focused on ML models in paediatric patients with haematological malignancies. Studies were categorised into thematic groups for analysis. Twenty studies, primarily on leukaemia, were included in this review. Studies were organised into thematic categories such as prognoses, treatment responses and toxicity predictions. Prognostic studies showed AUC scores between 0.685 and 0.929, indicating moderate-high predictive accuracy. Treatment response studies demonstrated AUC scores between 0.840 and 0.875, reflecting moderate accuracy. Toxicity prediction studies reported high accuracy with AUC scores from 0.870 to 0.927. Only five studies (25%) performed external validation. Significant heterogeneity was noted in ML tasks, reporting formats, and effect measures across studies, highlighting a lack of standardised reporting and challenges in data comparability. The clinical applicability of these ML models remains limited by the lack of external validation and methodological heterogeneity. Addressing these challenges through standardised reporting and rigorous external validation is needed to translate ML from a promising research tool into a reliable clinical practice component. Key message: Machine Learning (ML) significantly enhances predictive models in paediatric haematological cancers, offering new avenues for personalised treatment strategies. Future research should focus on developing ML models that can integrate with real-time clinical workflows. Addition to literature: Provides a comprehensive overview of current ML applications and trends. It identifies limitations to its applicability, including the limited diversity in datasets, which may affect the generalisability of ML models across different populations. Encourages standardisation and external validation in ML studies, aiming to improve patient outcomes through precision medicine in paediatric haematological oncology.

Novel Coumarin-Nucleobase Hybrids with Potential Anticancer Activity: Synthesis, In Vitro Cell-Based Evaluation, and Molecular Docking.

A new series of compounds planned by molecular hybridization of the nucleobases uracil and thymine, or the xanthine theobromine, with coumarins, and linked through 1,2,3-triazole heterocycles were evaluated for their in vitro anticancer activity against the human tumor cell lines: colon carcinoma (HCT116), laryngeal tumor cells (Hep-2), and lung carcinoma cells (A549). The hybrid compound 9a exhibited better activity in the series, showing an IC50 of 24.19 ± 1.39 μM against the HCT116 cells, with a selectivity index (SI) of 6, when compared to the cytotoxicity against the non-tumor cell line HaCat. The in silico search for pharmacological targets was achieved through molecular docking studies on all active compounds, which suggested that the synthesized compounds possess a high affinity to the Topoisomerase 1-DNA complex, supporting their antitumor activity. The in silico toxicity prediction studies suggest that the compounds present a low risk of causing theoretical mutagenic and tumorigenic effects. These findings indicate that molecular hybridization from natural derivative molecules is an interesting approach to seek new antitumor candidates.

Discovery of mTOR Receptor Modulators Targeting Breast Cancer by Hybrid of Virtual Screening and Molecular Docking Approach

This research paper presents a comprehensive approach integrating virtual screening and molecular docking to identify potential therapeutic candidates. Pharmacophore-based virtual screening was employed to assess the structural similarities of compounds to a reference molecule, revealing promising candidates with high similarity scores. Subsequently, molecular docking studies were conducted to predict the binding affinities of these compounds to the target receptor, 4DRH. CHEMBL3775006 emerged as a lead candidate, demonstrating both structural resemblance and strong binding affinity to the target protein. ADME studies highlighted its pharmacokinetic properties, while toxicity prediction studies provided insights into potential adverse effects. Overall, this study underscores the utility of virtual screening and molecular docking in identifying novel drug candidates with therapeutic potential.

Synthesis, antidiabetic activity and in silico studies of benzo[b]thiophene based small molecule α-amylase inhibitors

Benzo[b]thiophene has been implicated as molecular framework in the drug discovery against broad spectrum of biological targets. In the antidiabetic drug regime, benzo[b]thiophene based SGLT2 and ALR2 inhibitors have been recently developed but their potential towards α-amylase inhibition remained unexplored to date. In this context, a series of novel small molecule benzo[b]thiophene-2-carboxylic acid derivatives (3a-p) was synthesized, characterized, and evaluated for antidiabetic activity as α-amylase inhibitors. We found that, all benzo[b]thiophene derivatives exhibited significant α-amylase inhibition with IC50 value ranging from 5.37 ± 0.25 μM to 29.89 ± 0.68 μM. The SAR studies showed benzo[b]thiophene carboxylate bearing bis(2-hydroxyethyl)amino group (3b) was most potent with IC50 of 5.37 ± 0.25 μM compared to standard drug Acarbose (IC50 = 6.40 ± 0.14 μM). Further, the enzyme inhibition mechanism study regarded 3b as competitive inhibitor of α-amylase with Ki value of 1.76 μM. A detailed in silico study was also performed in order to estimate binding properties, drug likeness and predict toxicity profile of these agents. It was demonstrated that novel small molecule benzo[b]thiophene derivative (3b) can effectively bind through H-bonding, hydrophobic and π-stacking interactions within α-amylase active site. Moreover, drug likeness and toxicity prediction studies suggested compound 3b as potential & safter α-amylase inhibitor. Overall, our present study disclosed a novel class of benzo[b]thiophene based α-amylase inhibitors and opened a template for further lead optimization and development.

Synthesis, Computational and Antimicrobial Study of 2-(2-Hydrazinyl)thiazole Derivatives

In the present investigation, we report a combined computational and experimental study of eight thiazole derivatives (4a-4h) obtained from 3,4-dihydronaphthalen-1(2H)-one. A green chemistry protocol comprising PEG-400 and sulfamic acid was employed for the synthesis of eight diverse thiazole derivatives from 3,4-dihydronaphthalen-1(2H)-one, thiosemicarbazide and various phenacyl bromides. The synthetic strategy provides benefits like short reaction time, high yield, and non-chromatographic purification. The compounds were structurally confirmed on the basis of IR, 1HNMR and 13C NMR. The obtained thiazole derivatives were studied using the density functional theory (DFT) method employing B3LYP/6-311G(d,p) level of theory for optimization and Time-Dependent DFT (TD-DFT) approach for examining electronic energies and UV-Vis characteristics. Various computational parameters like bond length, bond angles, HOMO, LUMO, MESP, Mulliken charges, and global descriptors are obtained and discussed. The UV-Vis study the in gas phase and DMSO solvent was investigated to obtain various insights such as absorption energies oscillator strength, configurations and transitions of examined thiazole derivatives. The effect of polar solvent has augmented the absorption wavelength of all studied thiazole derivatives. The experimental and simulated UV-Vis data correlate with each other prompting the effectiveness of the computed method. The scaled and experimental wavenumbers provided the appropriate assignment of various vibrational signals. The antibacterial study was performed against E. coli, P. aeruginosa, and S. aureus which demonstrated the strong antibacterial potential against S. aureus. The antifungal study against C. albicans revealed that these compounds are poor antifungal agents. The DPPH and OH radical assays were used to establish the % radical scavenger effects and results showed that these derivatives are good antioxidant agents. The % hemolytic activity of the tested compounds showed that all compounds fall within the acceptable toxicity limit. Importantly in slico ADME and toxicity prediction studies of these compounds highlighted good ADME profile with no hepatotoxicity, immunotoxicity and cytotoxicity.

Mechanisms of 2,4,6-trichlorophenol removal by activated persulfate with hexagonal Fe7S8 sheets and enhancing removal by oxidizing porous media

Pyrrhotite (Fe7S8) is a natural mineral with multiple valence states of iron and an efficient peroxydisulfate (PS) activator. However, the activation mechanism of PS and the performance of 2,4,6-trichlorophenol (TCP) removal by the Fe7S8/PS system are not clear. Herein, the hexagonal Fe7S8 sheets were fabricated using the facile one-step solvothermal method, which could enhance PS activation and TCP degradation. The Fe7S8/PS system removed 94.3% of the TCP within 60 min with an apparent rate constant of 0.052 ± 0.003 min−1. The dissolution of Fe7S8 during the Fe7S8/PS activation facilitated the regeneration of Fe3+/Fe2+ redox cycles. Free radical species analysis confirmed the presence of sulfate radical (SO4•-) and hydroxyl radical (•OH). The fundamental involvement of the free radicals was observed in two stages. The first stage (0–5 min) was dominated by the contribution of •OH, whereas, in 2nd stage (5–60 min), the contribution of SO4•- exceeded that of •OH. Toxicity prediction studies revealed that degradation intermediates had lower toxicity than TCP. In the reaction column filled with 15 g of quartz sand (QS), the removal efficiency on TCP decreased from 100% to 0% over a period of 30 min to 80 h. In addition, after 155 h, the TCP removal efficiencies of column experiments loaded with 15, 18, and 20 g of QS and Fe7S8 were 33.2%, 44.6%, and 50.2%, respectively. These findings suggested the Fe7S8/PS system showed high potential for removing TCP from groundwater.

Synthesis, Anticancer Activity, and In Silico Studies of 5-(3-Bromophenyl)-N-aryl-4H-1,2,4-triazol-3-amine Analogs.

In the current study, we described the synthesis of ten new 5-(3-Bromophenyl)-N-aryl-4H-1,2,4-triazol-3-amine analogs (4a-j), as well as their characterization, anticancer activity, molecular docking studies, ADME, and toxicity prediction. The title compounds (4a-j) were prepared in three steps, starting from substituted anilines in a satisfactory yield, followed by their characterization via spectroscopic techniques. The National Cancer Institute (NCI US) protocol was followed to test the compounds' (4a-j) anticancer activity against nine panels of 58 cancer cell lines at a concentration of 10-5 M, and growth percent (GP) as well as percent growth inhibition (PGI) were calculated. Some of the compounds demonstrated significant anticancer activity against a few cancer cell lines. The CNS cancer cell line SNB-75, which showed a PGI of 41.25 percent, was discovered to be the most sensitive cancer cell line to the tested compound 4e. The mean GP of compound 4i was found to be the most promising among the series of compounds. The five cancer cell lines that were found to be the most susceptible to compound 4i were SNB-75, UO-31, CCRF-CEM, EKVX, and OVCAR-5; these five cell lines showed PGIs of 38.94, 30.14, 26.92, 26.61, and 23.12 percent, respectively, at 10-5 M. The inhibition of tubulin is one of the primary molecular targets of many anticancer agents; hence, the compounds (4a-j) were further subjected to molecular docking studies looking at the tubulin-combretastatin A-4 binding site (PDB ID: 5LYJ) of tubulin. The binding affinities were found to be efficient, ranging from -6.502 to -8.341 kcal/mol, with two major electrostatic interactions observed: H-bond and halogen bond. Ligand 4i had a binding affinity of -8.149 kcal/mol with the tubulin-combretastatin A-4 binding site and displayed a H-bond interaction with the residue Asn258. The ADME and toxicity prediction studies for each compound were carried out using SwissADME and ProTox-II software. None of the compounds' ADME predictions showed that they violated Lipinski's rule of five. All of the compounds were also predicted to have LD50 values between 440 and 500 mg/kg, putting them all in class IV toxicity, according to the toxicity prediction. The current discovery could potentially open up the opportunity for further developments in cancer.

Towards novel tacrine analogues: Pd(dppf)Cl2·CH2Cl2 catalyzed improved synthesis, in silico docking and hepatotoxicity studies.

A plethora of 6-(hetero)aryl C–C and C–N bonded tacrine analogues has been made accessible by employing palladium mediated (Suzuki–Miyaura, Heck, Sonogashira, Stille and Buchwald) cross-coupling reactions, starting from either halogenated or borylated residues. The successful use of Pd(dppf)Cl2·CH2Cl2 as a common catalytic system in realizing all these otherwise challenging transformations is the highlight of our optimized protocols. The analogues thus synthesized allow the available chemical space around the C-6 of this biologically relevant tacrine core to be explored. The in silico docking studies of the synthesized compounds were carried out against the acetylcholinesterase (AChE) enzyme. The hepatotoxicity studies of these compounds were done against complexes of CYP1A2 and CYP3A4 proteins with known inhibitors like 7,8-benzoflavone and ketoconazole, respectively.

Citronellal suppress the activity of ornithine decarboxylase in hypopharyngeal carcinoma cells

Citronellal, an acyclic monoterpene with an aldehyde group, is present in many plants, including species of Eucalyptus, Corymbia, Cymbopogon, Coriandrum. It is also known as rhodinol and possesses strong insect repellant and antifungal properties. In this study, we investigated the antiproliferative action of citronellal on hypopharyngeal carcinoma (FaDu) and normal (HEK-293) cell lines. Citronellal suppresses the activity of ornithine decarboxylase (ODC: 77.12±10.73 µM) and inhibits the proliferation of FaDu cells with an IC50 of 71.81±3.37 µM. The qRT-expression analysis depicts citronellal down-regulate the expression of ODC, and a robust binding interaction of citronellal with ODC was observed in molecular docking studies. Further, it also arrests the G2/M phase of FaDu cells, followed by an increase in the number of sub-diploid cells but was non-toxic to normal cell line. The toxicity prediction studies revealed citronellal follows the Lipinski rule of 5 and the Ghose rule. These observations provide experimental evidence for citronellal to be used as a new prototype for designing ODC inhibitors.

Benzosuberene-sulfone analogues synthesis from Cedrus deodara oil and their therapeutic evaluation by computational analysis to treat type 2 diabetes

Benzosuberene-sulfone (BSS) analogues have been semi-synthesized following green approaches from himachalenes, which has been extracted from essential oil of Cedrus deodara. In this process, benzosuberene in presence of different aryl or alkyl sodium sulfinates, I2 and potassium persulfate (K2S2O8) in acetonitrile–water solvent conditions gave BSS-analogues at room temperature. Under this reaction, a facile endocyclic β-H elimination has been noticed for BSS-analogues synthesis instead of vinyl sulfones and the reason may be due to its specific structure and electronic environment. The BSS-compounds were obtained with moderate to excellent yields under mild conditions. All the compounds were computationally subjected to drug likeliness and toxicity prediction studies. Further, the synthesized molecules were evaluated under in-silico studies for their binding affinity towards the native Peroxisome Proliferator-Activated Receptor Gamma (PPARG), and two PPARG mutants (R357A and V290M). Both the mutant forms of PPARG are deficient in eliciting a response to treatment with full and partial agonists. Our computational studies suggested that the molecule 3q performed better than the standard drug (Rosiglitazone) in all three protein structures. This implies that our suggested molecule could act as a more potent antagonist to native PPARG and could also be developed to treat type-2 diabetes patients with R357A and V290M mutations, which didn’t elicit any response to currently available drugs in the market.

A Toxicity Prediction Tool for Potential Agonist/Antagonist Activities in Molecular Initiating Events Based on Chemical Structures.

Because the health effects of many compounds are unknown, regulatory toxicology must often rely on the development of quantitative structure–activity relationship (QSAR) models to efficiently discover molecular initiating events (MIEs) in the adverse-outcome pathway (AOP) framework. However, the QSAR models used in numerous toxicity prediction studies are publicly unavailable, and thus, they are challenging to use in practical applications. Approaches that simultaneously identify the various toxic responses induced by a compound are also scarce. The present study develops Toxicity Predictor, a web application tool that comprehensively identifies potential MIEs. Using various chemicals in the Toxicology in the 21st Century (Tox21) 10K library, we identified potential endocrine-disrupting chemicals (EDCs) using a machine-learning approach. Based on the optimized three-dimensional (3D) molecular structures and XGBoost algorithm, we established molecular descriptors for QSAR models. Their predictive performances and applicability domain were evaluated and applied to Toxicity Predictor. The prediction performance of the constructed models matched that of the top model in the Tox21 Data Challenge 2014. These advanced prediction results for MIEs are freely available on the Internet.

Biological Safety Studies and Simultaneous Determination of Linagliptin and Synthetic Impurities by LC-PDA.

A stability-indicating LC method was developed for quantification of linagliptin (LGT) and three synthetic impurities. The method utilizes a Thermo Scientific® RP-8 column (100 mm × 4.6 mm; 5 μm) with the PDA detector for quantitation of impurities. A mixture of 0.1% formic acid with pH 3.5 (A) and acetonitrile (B) was used as the mobile phase at a flow rate of 0.6 mL·min−1 with gradient elution. The percentage of mobile phase B increases from 30% to 70% over 5 min and decreases from 70% to 30% between 5 and 8 min. The method was validated according to International Council for Harmonization (ICH) guidelines. The LOD values obtained were 0.0171 μg·mL−1 and 0.015 μg·mL−1 for LGT and impurities, respectively. The LOQ values were 0.06 μg·mL−1 for LGT and impurities. In all cases, the correlation coefficients of LGT and impurities were >0.999, showing the linearity of the method. The % recovery of the LGT and added impurity were in the range of 92.92–99.79%. The precision of the method showed values less than 1.47% for LGT and less than 4.63% for impurities. The robustness was also demonstrated by small modifications in the chromatographic conditions. The selectivity was evidenced because the degradation products formed in stress conditions did not interfere in the determination of LGT and impurities. Toxicity prediction studies suggested toxicity potential of the impurities, which was confirmed using biological safety studies in vitro.

Synthesis and biological evaluation of 1,3-dioxolane-based 5-HT1A receptor agonists for CNS disorders and neuropathic pain.

Targeting 5-HT1A receptor (5-HT1AR) as a strategy for CNS disorders and pain control. A series of 1,3-dioxolane-based 2-heteroaryl-phenoxyethylamines was synthesized by a convergent approach and evaluated at α1-adrenoceptors and 5-HT1AR by binding and functional experiments. Absorption, distribution, metabolism, excretion and toxicity prediction studies were performed to explore the drug-likeness of the compounds. The most promising compound, the pyridin-4-yl derivative, emerged as a potent and selective 5-HT1AR agonist (pKi=9.2; pD2=8.83; 5-HT1A/α1=135). In vitro it was able to permeate by passive diffusion MDCKII-MDR1 monolayer mimicking the blood-brain barrier and showed promising neuroprotective activity.

LC/QTOF/MS/MS characterization, molecular docking and in silico toxicity prediction studies on degradation products of anagliptin

Pharmaceutical drugs are potential molecules with specific biological activity. However, long-term use of these chemical molecules can affect the human physiological system because of their increased levels in the human body. Therefore, identification and structure elucidation of impurities or degradation products should be taken into consideration in order to assure drug safety. The present study assessed the degradation behaviour of dipeptidyl peptidase-4 (DPP-4) inhibitor anagliptin under different stress conditions as per ICH guidelines Q1A (R2) followed by elucidation of the structure of degradation products. All the stress samples were analysed by using UPLC/PDA. The superior separation of drug from its degradation products was attained with time programmed gradient elution on BEH C18 (100 mm × 2.1 mm, 1.7 μm) column using 10 mM ammonium formate (aqueous) and acetonitrile (organic) as the mobile phase components. All the degradation products of anagliptin were characterized using LC/QTOF/MS/MS. In addition, the activity and toxicity of degradation products were determined through molecular docking and in silico toxicity prediction studies, respectively. The developed UPLC/PDA method was validated as per ICH guidelines in terms of specificity, accuracy, precision, linearity and robustness.

In silico validation of the indigenous knowledge of the herbal medicines among tribal communities in Sathyamangalam wildlife sanctuary, India

The ethno-botanical documentation among ethnic people in Sathyamangalam wildlife sanctuary, Tamil Nadu, India has been investigated for the first time. A total of 61 medicinal plants having new combination uses were reported with adjuvant in the treatment of dermatological, Genitourinary and gastrointestinal ailments. This study could help in the recovery and conservation of traditional medicine system among educated generation. The present study was aimed to: (1) documentation of the traditional knowledge (2) quantitative analysis using Use value (UV), Informant consensus factor (ICF), Index of agreement on remedies (IAR), Relative frequency citation (RFC) and Cultural Importance index (CII) (3) validation of ethno-botanical data using in silico biological activity and toxicity prediction studies. Semi-structured direct interviews were conducted to acquire information from the study area tribes. Total of 89 tribes including both gender among various communities were interviewed and their ethno-botanical knowledge was documented. The data were assessed using ethno-botanical indices methods to estimate the consistency of usage herbal knowledge in various ailments. A total of 61 species were recorded for treatment of categorized ailments. The collected medicinal information from ethnic groups shows remarkable new usage of medicinal plants to particular ailments. Our comparative in silico studies also supported the traditional medicine results with correspondence to their bioactive. Traditional knowledge of ethnic people also linked to their culture and history. This study also infers the usage of traditional plant based medicine. Further research related to the bioactivities of reported plants should be encouraged to explore the importance in pharmaceutical industry.

Design, Synthesis, and Biological Evaluation of Vanillin Hydroxamic Acid Derivatives as Novel Peptide Deformylase Inhibitors.

Infectious disease is increasingly hampering human health, which challenge the discovery of new antibacterial target. Peptide deformylase (PDF), a metalloenzyme responsible for catalyzing the removal of the N-formyl group from nascent proteins, was considered as an important target in antibacterial drug discovery. Reported here are the design, synthesis and biological evaluation of vanillin hydroxamic acid derivatives. Analysis of the structure-activity relationships lead to the discovery of compound 8, which exhibits promising antibacterial activity against Escherichia coli, Staphylococcus aureus, Aspergillus oryzae, and Aspergillus foetidus with the MIC value of 0.32 µg/ml, 0.32 µg/ml, 0.16 µg/ml and 0.16 µg/ml, respectively. Furthermore, molecular docking study was applied to elucidate binding interaction between compound 8 and PDF, which indicate that compound 8 not only shares the same binding pocket with actinonin, but also has a similar binding pattern. In silico pharmacokinetic and toxicity prediction studies also suggested that compound 8 has a relatively high drug score of 0.80, and has no risk of toxicity. Compound 8 might represent a promising scaffold for the further development of novel antibacterial drugs.

Design, synthesis, in silico and in vitro evaluation of thiophene derivatives: A potent tyrosine phosphatase 1B inhibitor and anticancer activity

A series of novel methyl 4-(4-amidoaryl)-3-methoxythiophene-2-carboxylate derivatives were designed against the active site of protein tyrosine phosphatise 1B (PTP1B) enzyme using MOE.2008.10. These molecules are also subjected for in silico toxicity prediction studies and considering their corresponding drug scores, it implied that, the molecules are promising as anticancer agents. The designed compounds were synthesized by using suitable methods and characterized. They were subjected to inhibitory activity against PTP1B and in vitro anticancer activity by MTT assay. Most of the tested compounds showed potent inhibitory activity against PTP1B, among the compounds tested, compound 5b exhibited the highest activity (IC50=5.25µM) and remarkable cytotoxic activity at 0.09µM of IC50 against the MCF-7 cell line. In addition to this, compound 5c also showed potential anticancer activity at 2.22µM of IC50 against MCF-7 and 0.72µM against HepG2 cell lines as well as PTP1B inhibitory activity at IC50 of 6.37µM.

Ligand and Structure-Based Approaches for the Identification of Peptide Deformylase Inhibitors as Antibacterial Drugs.

Peptide deformylase (PDF) is a metalloprotease catalyzing the removal of a formyl group from newly synthesized proteins, which makes it an important antibacterial drug target. Given the importance of PDF inhibitors like actinonin in antibacterial drug discovery, several reported potent PDF inhibitors were used to develop pharmacophore models using the Galahad module of Sybyl 7.1 software. Generated pharmacophore models were composed of two donor atom centers, four acceptor atom centers and two hydrophobic groups. Model-1 was screened against the Zinc database and several compounds were retrieved as hits. Compounds with Qfit values of more than 60 were employed to perform a molecular docking study with the receptor Escherichia coli PDF, then compounds with docking score values of more than 6 were used to predict the in silico pharmacokinetic and toxicity risk via OSIRIS property explorer. Two known PDF inhibitors were also used to perform a molecular docking study with E. coli PDF as reference molecules. The results of the molecular docking study were validated by reproducing the crystal structure of actinonin. Molecular docking and in silico pharmacokinetic and toxicity prediction studies suggested that ZINC08740166 has a relatively high docking score of 7.44 and a drug score of 0.78.

Proteomic analysis of the rat liver

Rat is a useful, widely used animal model for biological and toxicity studies. We analyzed total and cytosolic rat liver proteins by applying proteomics technologies. The proteins were separated by two-dimensional electrophoresis employing broad and narrow range immobilized pH gradient strips, followed by MALDI-MS analysis of the tryptic digests. Two hundred and seventy-three different gene products were identified, of which approximately 60% were enzymes with a broad spectrum of catalytic activities. Most of the identified proteins were detected in other rat protein samples as well, which were analyzed in our laboratory. Fifteen gene products were detected for the first time. These were represented by one spot each, whereas most of the frequently detected proteins were represented by multiple spots. In average, approximately five to 10 spots corresponded to one gene product. The database includes a large number of proteins known to be involved in toxicology-relevant pathways and may be useful in toxicity prediction studies.