Simple Method of Calculating Octanol/Water Partition Coefficient.

Our study aimed to develop a method to mathematically predict the kinetic parameters K 1 (influx rate constant), k 2 (efflux rate constant), and BP ND (nondisplaceable binding potential) of amyloid PET tracers and obtain SUV ratios (SUVRs) from predicted timeactivity curves of target and reference regions. Methods: We investigated 10 clinically applied amyloid PET radioligands: 11 CPittsburgh compound B, 11 C-BF-227, 11 C-AZD2184, 11 C-SB-13, 18 F-FACT, 18 F-florbetapir, 18 F-florbetaben, 18 F-flutemetamol, 18 F-FDDNP, and 18 F-AZD4694. For each tracer, time-activity curves of both target and reference regions were generated using a simplified 1-tissue-compartment model, with an arterial plasma input function and the predicted kinetic parameters. K 1 , k 2 , and BP ND were derived from the lipophilicity (logP), apparent volume, free fraction in plasma, free fraction in tissue, dissociation constant, and density of amyloid b using biomathematic modeling. Density was fixed at 3 nM to represent healthy control conditions and 50 nM to represent severe Alzheimer disease (AD). Predicted SUVRs for the healthy and AD groups were then obtained by dividing the integrated time-activity curve of the target region by that of the reference region. To validate the presented method, the predicted K 1 , k 2 , BP ND , and SUVR for the healthy and AD groups were compared with the respective clinically observed values. Results: The correlation between predicted and clinical kinetic parameters had an R 2 value of 0.73 for K 1 in the healthy group, 0.71 for K 1 in the AD group, 0.81 for k 2 in the healthy group, 0.85 for k 2 in the AD group, and 0.63 for BP ND in the AD group. The regression relationship between the predicted SUVR (y) and the clinical SUVR (x) for the healthy and the AD groups was y 5 2.73x -2.11 (R 2 5 0.72). Conclusion:The proposed method showed a good correlation between predicted and clinical SUVR for the 10 clinically applied amyloid tracers.

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“…Instead of clogD in Equation 3, we used the in silico Moriguchi logP (22). K 1 was then calculated as detailed in Equation 2.…”

Section: Prediction Of Clinical Suvr In Amyloid Pet Imagingmentioning

confidence: 99%

Prediction of the Clinical SUV Ratio in Amyloid PET Imaging Using a Biomathematic Modeling Approach Toward the Efficient Development of a Radioligand

et al. 2017

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“…These descriptors are representative of the four dominant interaction forces, electrostatic, hydrogen bond acceptor, hydrogen bond donor and hydrophobicity, and size and shape of the compounds, respectively. S is the combined dipolarity/polarizability, nHAcc and nHDon are the number of acceptor and donor atoms for hydrogen bonds, respectively, MLOGP is the Moriguchi Log P, 70 MW is the molecular weight, and SPH is the spherosity. The average values of these four descriptors for P+ and P-compounds of all of the various datasets are given in Table 8.…”

Section: Discussionmentioning

confidence: 99%

Prediction of Cytochrome P450 3A4, 2D6, and 2C9 Inhibitors and Substrates by Using Support Vector Machines

Yap

Chen

2005

J. Chem. Inf. Model.

152

185

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Statistical learning methods have been used in developing filters for predicting inhibitors of two P450 isoenzymes, CYP3A4 and CYP2D6. This work explores the use of different statistical learning methods for predicting inhibitors of these enzymes and an additional P450 enzyme, CYP2C9, and the substrates of the three P450 isoenzymes. Two consensus support vector machine (CSVM) methods, "positive majority" (PM-CSVM) and "positive probability" (PP-CSVM), were used in this work. These methods were first tested for the prediction of inhibitors of CYP3A4 and CYP2D6 by using a significantly higher number of inhibitors and noninhibitors than that used in earlier studies. They were then applied to the prediction of inhibitors of CYP2C9 and substrates of the three enzymes. Both methods predict inhibitors of CYP3A4 and CYP2D6 at a similar level of accuracy as those of earlier studies. For classification of inhibitors of CYP2C9, the best CSVM method gives an accuracy of 88.9% for inhibitors and 96.3% for noninhibitors. The accuracies for classification of substrates and nonsubstrates of CYP3A4, CYP2D6, and CYP2C9 are 98.2 and 90.9%, 96.6 and 94.4%, and 85.7 and 98.8%, respectively. Both CSVM methods are potentially useful as filters for predicting inhibitors and substrates of P450 isoenzymes. These methods generally give better accuracies than single SVM classification systems, and the performance of the PP-CSVM method is slightly better than that of the PM-CSVM method.

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“…18) The number of H-bond donors was obtained by counting the numbers of OH and NH bonds in each molecule. H-bond acceptors are the sum of the numbers of nitrogen and oxygen atoms, as described by Lipinski et al, 3) except for the nitrogen atom in NO 2 in the present study.…”

Section: Calculation Of the Parametersmentioning

confidence: 99%

Unexpected plant-systemic insecticidal properties of alkylene-tethered bis-imidacloprid derivatives

et al. 2010

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Alkylene-tethered bis-imidacloprid (bis-IMI) derivatives were evaluated for insecticidal activity after foliar dipping, foliar spraying and under systemic conditions. Insecticidal activity on the dipped leaves was dependent on the tether length, and heptamethylene (C7) and octamethylene (C8) derivatives, their best compounds, almost completely controlled the green peach aphid (Myzus persicae) at 10 mg l Ϫ1, while all divalent compounds were weak against the tobacco cutworm (Spodoptera litura). C6 and C7 derivatives were examined for residual and systemic activity. Complete control of the green peach aphid by both compounds was observed on evaluation 72 hr after insect release on the eleventh day after foliar treatment, and the C7 derivative showed distinguished systemic activity against the brown plant hopper (N. Lugens) and the green peach aphid. The bis-IMIs should be disqualified as insecticidal candidates on virtual screening criteria owing to its high log P value, large molecular mass and excessive numbers of hydrogen-bond acceptors and rotatable bonds. Additional criteria may be necessary to account for the plant-mobile insecticidal behavior of such novel structures as bis-IMIs.

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Simple Method of Calculating Octanol/Water Partition Coefficient.

Cited by 489 publications

References 1 publication

Prediction of the Clinical SUV Ratio in Amyloid PET Imaging Using a Biomathematic Modeling Approach Toward the Efficient Development of a Radioligand

Prediction of the Clinical SUV Ratio in Amyloid PET Imaging Using a Biomathematic Modeling Approach Toward the Efficient Development of a Radioligand

Prediction of Cytochrome P450 3A4, 2D6, and 2C9 Inhibitors and Substrates by Using Support Vector Machines

Unexpected plant-systemic insecticidal properties of alkylene-tethered bis-imidacloprid derivatives

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