docking

Tris(2,4-di-tert-butylphenyl)phosphate (TDTBPP) isolated from Vitex negundoL inhibits secretory phospholipase A2 (sPLA2). Tris(2,4-di-tert-butylphenyl)phosphate has anti-inflammatory activity.

Toyocamycin (Vengicide) is an adenosine analog produced by Actinomycetes, functioning as an XBP1 inhibitor and inhibiting IRE1α-induced ATP-dependent XBP1 mRNA cleavage (IC50: 80 nM), and induces apoptosis.

Guanosine 5'-triphosphate trisodium salt (5'-GTP trisodium salt) activates signal-transducing G proteins involved in cellular processes such as proliferation, differentiation, and activation of intracellular kinase cascades. It regulates proliferation and apoptosis through the hydrolysis by small GTPases Ras and Rho, and plays a role in vesicle docking, fusion, and formation via Rab. Additionally, GTP serves as an energy-rich precursor for the biosynthesis of DNA and RNA.

1-Ethyl-4-methylbenzene exhibits molecular docking activity against T4 lysozyme (Kd = 120 μM) and can be used in biochemical experiments and drug synthesis.

1-Ethyl-2-methylbenzene has molecular docking activity against t4 lysozyme (Kd=505μM) and can be used in biochemical experiments and drug synthesis.

PDK1-IN-RS2 inhibits the activation of the downstream kinases S6K1 by PDK1. PDK1-IN-RS2 is a mimic of the peptide docking motif (PIFtide) and is a substrate-selective PDK1 inhibitor (Kd: 9 μM).

Mcl-1 inhibitor20 (compound 47) is an Mcl-1 antagonist with anti-leukemia properties. It binds to the BH3 docking groove of Mcl-1 (Ki=24 nM), occupies the P1 pocket, and interacts with Lys234 and Val249. Mcl-1 inhibitor20 also exhibits good microsomal stability, favorable pharmacokinetic properties, and low cardiotoxicity.

Guanosine triphosphate tritris (GTP tritris) serves as a crucial enhancer in myocyte differentiation, playing an essential role in regulating miRNA-muscle regulatory factors. It promotes the release of exosomes rich in guanine and guanine-derived molecules, and is considered an activation precursor for RNA synthesis. In mitochondrial functionality, GTP is involved in the entry of proteins into the matrix, which is vital for various regulatory pathways. It initiates peptide synthesis by facilitating the binding of formylmethionine-tRNA to the ribosome, and aids in polypeptide chain elongation. Additionally, GTP acts as a carrier for phosphates and pyrophosphates, channeling chemical energy into specific biosynthetic pathways. It activates signal transduction G proteins, regulates cellular processes such as proliferation and differentiation, and its hydrolysis by small GTPases (including Ras and Rho) is indispensable for both proliferation and apoptosis. Furthermore, the small GTPase Rab assists in vesicle docking, fusion, and formation. Beyond signal transduction, GTP is also an energy-rich precursor in the biosynthesis of DNA and RNA enzymes.

Holanamine is a compound used to combat Leishmania donovani and has been identified as a non-competitive inhibitor of LdToP1B. Docking studies reveal that Holanamine exerts its antileishmanial effects through hydrogen bonds and hydrophobic interactions with the N-terminal and hinge regions of the LTop1B large subunit.

VR17-04, a metabolite of Enisamium, inhibits the incorporation of GTP and UTP during RNA synthesis. Its mechanism of action was elucidated through docking and molecular dynamics simulations. These findings suggest that VR17-04 could serve as a potential antiviral strategy for managing COVID-19.

PSB-22269 is identified as a GPR17 antagonist with a Ki value of 8.91 nM. It exhibits significant inhibitory effects in cAMP and G protein activation assays. Molecular docking studies indicate that the binding site of PSB-22269 includes positively charged arginine residues and a hydrophobic pocket. PSB-22269 promotes myelin regeneration strategies, offering potential for multiple sclerosis research.

Δ8-THC methyl ether (compound 3) demonstrates a strong docking score of -10.167 kcal/mol for the CB2 receptor. Additionally, Δ8-THC methyl ether exhibits antinociceptive activity in mice.

XT17 is an anthrone compound with broad-spectrum antibacterial activity, exerting its effects by disrupting the cell wall and inhibiting DNA synthesis. It demonstrates weak hemolytic activity, low cytotoxicity to mammalian cell lines, and a low rate of resistance development. Additionally, XT17 shows in vivo efficacy in a mouse corneal infection model induced by Staphylococcus aureus or Pseudomonas aeruginosa. Further docking studies confirm that XT17 forms a stable complex with bacterial gyrase. XT17 is suitable for research in the field of anti-infective agents.

Antifungalagent 129 (Compound 4g) acts as an inhibitor against Rhizoctonia solani, with an EC50 value of 4.27 mg/L. It shows effective control of rice sheath blight in both in vitro and in vivo studies. Preliminary investigations using scanning electron microscopy, molecular docking, enzyme activity assays, and cytotoxicity tests suggest that Antifungalagent 129 may exert its inhibitory action by affecting the cell structure or physiological processes of Rhizoctonia solani. This compound has potential applications in agricultural research related to plant diseases caused by Rhizoctonia solani, such as rice sheath blight.

BACE-1/Mpro-IN-1 is a compound capable of penetrating the blood-brain barrier, acting as a dual inhibitor for BACE-1 (IC50 = 0.26 μM) and SARS-CoV-2 Mpro (IC50 = 0.91 μM). It functions as a mixed inhibitor by binding to aspartic and cysteine proteases and demonstrates optimal docking scores alongside robust interaction characteristics. BACE-1/Mpro-IN-1 is applicable in research focusing on COVID-19-related neuroinflammation and Alzheimer’s disease.

DEMAMP is an antioxidant with the ability to scavenge DPPH and H2O2 free radicals, exhibiting IC50 values of 0.60 and 0.48 mg/mL, respectively. Molecular docking simulations suggest that DEMAMP effectively inhibits NADPH oxidase and the SARS-CoV-2 proteins Mpro and RdRp. Additionally, ADMET analysis confirms its good oral bioavailability. DEMAMP is applicable in studies related to COVID-19.

(5E)-7-Oxozeaenol is a resorcylic acid lactone that has been found in the fungus MSX 63935 and has enzyme inhibitory and anticancer activities.1,2 It inhibits TGF-β-activated kinase 1 (TAK-1; IC50 = 1.3 μM).1 (5E)-7-Oxozeaenol inhibits proliferation of MCF-7, H460, SF-268, HT-29, and MDA-MB-435 human cancer cells with IC50 values of 4.9, 1.2, 5.6, 4.4, and 5.5 μM, respectively.2 |1. Fakhouri, L., El-Elimat, T., Hurst, D.P., et al. Isolation, semisynthesis, covalent docking and transforming growth factor beta-activated kinase 1 (TAK1)-inhibitory activities of (5Z)-7-oxozeaenol analogues. Bioorg. Med. Chem. 23(21), 6993-6999 (2015).|2. Ayers, S., Graf, T.N., Adcock, A.F., et al. Resorcylic acid lactones with cytotoxic and NF-κB inhibitory activities and their structure-activity relationships. J. Nat. Prod. 74(5), 1126-1131 (2011).

(1S)-Calcitriol (1α,25-Dihydroxy-3-epi-vitamin-D3), a natural metabolite of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), exerts potent actions through vitamin D receptor (VDR) activation, including the inhibition of keratinocyte growth and suppression of parathyroid hormone secretion [1].

Celecoxib carboxylic acid is an inactive metabolite of the COX-2 inhibitor celecoxib .1,2It is formed from celecoxib primarily by the cytochrome P450 (CYP) isoform CYP2C9. 1.Liu, H., Huang, X., Shen, J., et al.Inhibitory mode of 1,5-diarylpyrazole derivatives against cyclooxygenase-2 and cyclooxygenase-1: Molecular docking and 3D QSAR analysesJ. Med. Chem.45(22)4816-4827(2002) 2.Kim, S.-H., Kim, D.-H., Byeon, J.-Y., et al.Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of celecoxib and its carboxylic acid metaboliteArch. Pharm. Res.40(3)382-390(2017)

Roccellic acid is a lichen secondary metabolite that has been found in R. montagnei and has antibacterial and anticancer activities.1,2 It is active against the bacteria S. gordonii and P. gingivalis (MIC = 46.9 μg/ml for both).1 Roccellic acid (100 μg/ml) inhibits proliferation of MDA-MB-231, MCF-7, and DLD-1 cancer cells by 65.3, 75.8, and 87.9%, respectively.2 |1. Sweidan, A., Chollet-Krugler, M., Sauvager, A., et al. Antibacterial activities of natural lichen compounds against Streptococcus gordonii and Porphyromonas gingivalis. Fitoterapia 121, 164-169 (2017).|2. Mishra, T., Shukla, S., Meena, S., et al. Isolation and identification of cytotoxic compounds from a fruticose lichen Roccella montagnei, and it's in silico docking study against CDK-10. Rev. Bras. Farmacogn. 27(6), 724-728 (2017).

DSPE-PEG(2000)-amine is a PEGylated derivative of 1,2-distearoyl-sn-glycero-3-PE . It has been used in the synthesis of solid lipid and thermosensitive liposomal nanoparticles for the delivery of anticancer agents.1,2,3DSPE-PEG(2000)-amine has also been used in the synthesis of fluorescein isothiocyanate-loaded mesoporous silica nanoparticles for imaging applications.4It can be conjugated to a variety of functional molecules for improved cellular targeting and uptake of DSPE-PEG(2000)-amine-containing nanoparticles.4,5 1.Sloat, B.R., Sandoval, M.A., Li, D., et al.In vitro and in vivo anti-tumor activities of a gemcitabine derivative carried by nanoparticlesInt. J. Pharm.409(1-2)278-288(2011) 2.Abd-Rabou, A.A., Bharali, D.J., and Mousa, S.A.Taribavirin and 5-fluorouracil-loaded pegylated-lipid nanoparticle synthesis, p38 docking, and antiproliferative effects on MCF-7 breast cancerPharm. Res.35(4)76(2018) 3.Affram, K., Udofot, O., Singh, M., et al.Smart thermosensitive liposomes for effective solid tumor therapy and in vivo imagingPLoS One12(9):e0815116(2017) 4.Wang, L.-S., Wu, L.-C., Lu, S.-Y., et al.Biofunctionalized phospholipid-capped mesoporous silica nanoshuttles for targeted drug delivery: Improved water suspensibility and decreased nonspecific protein bindingACS Nano4(8)4371-4379(2010) 5.Wen, X., Wang, K., Zhao, Z., et al.Brain-targeted delivery of trans-activating transcriptor-conjugated magnetic PLGA/lipid nanoparticlesPLoS One9(9):e106652(2014)

ARN24139 is a topoisomerase II poison (IC50= 7.3 μM in a topoisomerase II decatenation assay).1It inhibits proliferation of DU145, HeLa, and A549 cells (IC50s = 4.7, 3.8, and 3.1 μM, respectively). 1.Arencibia, J.M., Brindani, N., Franco-Ulloa, S., et al.Design, synthesis, dynamic docking, biochemical characterization, and in vivo pharmacokinetics studies of novel topoisomerase II poisons with promising antiproliferative activityJ. Med. Chem.63(7)3508-3521(2020)

Songorine (Napellonine) shows favorable anti-tumor activity in preliminary pharmacological verification trials including cell proliferation and molecular docking assays.

JWH-176 is a cannabimimetic indene hydrocarbon, exhibiting high affinity for the central cannabinoid (CB1) receptor (Ki= 26 nM), originally synthesized to investigate hydrogen bonding and aromatic stacking's roles in CB1 receptor docking studies. Intended for forensic and research applications, this compound's design facilitates the exploration of CB1 receptor interactions.