Abstract：
:A deep convolutional generative adversarial network (dcGAN) model was developed in this study to screen and design target-specific novel compounds for cannabinoid receptors. In the adversarial process of training, two models, the discriminator D and the generator G, are iteratively trained. D is trained to discover the hidden patterns among the input data to have the accurate discrimination of the authentic compounds and the "fake" compounds generated by G; G is trained to generate "fake" compounds to fool the well-trained D by optimizing the weights for matrix multiplication of data sampling. In order to determine the appropriate architecture and the input data structure for the involved convolutional neural networks (CNNs), the combinations of various network architectures and molecular fingerprints were explored. Well-developed CNN models including LeNet-5, AlexNet, ZFNet, and VGGNet were investigated. Four types of fingerprints, including MACCS, ECFP6, AtomPair, and AtomPair Count, were calculated to describe the small molecules with diverse structural characteristics. The limitation of generating fingerprints as output remains that the concrete molecular structures cannot be converted directly, while the generative models with convolutional networks provide promising opportunities to the screening of molecules and rational modifications afterward. This study demonstrated how computer-aided drug discovery could benefit from the recent advances in deep learning.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Bian Y,Wang J,Jun JJ,Xie XQdoi
10.1021/acs.molpharmaceut.9b00500subject
Has Abstractpub_date
2019-11-04 00:00:00pages
4451-4460issue
11eissn
1543-8384issn
1543-8392journal_volume
16pub_type
杂志文章abstract：:The drug-induced accumulation of phospholipids in lysosomes of various tissues is predominantly observed in regular repeat dose studies, often after prolonged exposure, and further investigated in mechanistic studies prior to candidate nomination. The finding can cause delays in the discovery process inflicting high c...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00388
更新日期：2017-12-04 00:00:00
abstract：:Generation 5 poly(amidoamine) (G5 PAMAM) methotrexate (MTX) conjugates employing two small molecular linkers, G5-(COG-MTX)n, G5-(MFCO-MTX)n were prepared along with the conjugates of the G5-G5 (D) dimer, D-(COG-MTX)n, D-(MFCO-MTX)n. The monomer G5-(COG-MTX)n conjugates exhibited only a weak, rapidly reversible binding...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp500608s
更新日期：2014-11-03 00:00:00
abstract：:Antiviral drugs often suffer from poor intestinal permeability, preventing their delivery via the oral route. The goal of this work was to enhance the intestinal absorption of the low-permeability antiviral agents zanamivir heptyl ester (ZHE) and guanidino oseltamivir (GO) utilizing an ion-pairing approach, as a criti...
journal_title：Molecular pharmaceutics
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doi：10.1021/mp100050d
更新日期：2010-08-02 00:00:00
abstract：:In humans, C-X-C chemokine receptor type 4 (CXCR4) is a protein that is encoded by the CXCR4 gene and binds the ligand CXCL12 (also known as SDF-1). The CXCR4-CXCL12 interaction in cancer elicits biological activities that result in tumor progression and has accordingly been the subject of significant investigation fo...
journal_title：Molecular pharmaceutics
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abstract：:Viral nanotechnology is an emerging and highly interdisciplinary field in which viral nanoparticles (VNPs) are applied in diverse areas such as electronics, energy and next-generation medical devices. VNPs have been developed as candidates for novel materials, and are often described as "programmable" because they can...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章,评审
doi：10.1021/mp100225y
更新日期：2011-02-07 00:00:00
abstract：:A series of poorly soluble BCS class II compounds with "grease ball" characteristics were assessed for solubility and dissolution rate in biorelevant dissolution media (BDM) with the purpose of investigating which molecular structures gain most in solubility when dissolved under physiologically relevant conditions. Th...
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doi：10.1021/mp100049m
更新日期：2010-10-04 00:00:00
abstract：:Despite significant potential of oligonucleotides (ONs) for therapeutic and diagnostic applications, rapid and widespread intracellular delivery of ONs in cells situated in tissues such as skin, head and neck cavity, and eye has not been achieved. This study was aimed at evaluating the synergistic combination of micro...
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pub_type： 杂志文章
doi：10.1021/mp300717f
更新日期：2013-08-05 00:00:00
abstract：:Oleanolic acid (OA) is a well-known pentacyclic triterpenoid compound, which has been used as a dietary supplement and is supplied as an over-the-counter drug for the treatment of human liver diseases. These are reasons for the low bioavailability of OA which have restricted its wider application. In this study, two O...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.6b00129
更新日期：2016-05-02 00:00:00
abstract：:Graphene-based tumor cell nuclear targeting fluorescent nanoprobes (GTTNs) were synthesized in our laboratory as a kind of nanomaterial and showed good performance for both in vivo and in vitro imaging. GTTNs directly cross the cell membrane and specifically target the tumor cell nucleus via a cell membrane permeabili...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.0c00380
更新日期：2020-07-06 00:00:00
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journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00252
更新日期：2017-12-04 00:00:00
abstract：:PLGA was functionalized with PEG and biotin using click chemistry to generate a biotin receptor targeted copolymer (biotinylated-PEG-PLGA) which in turn was used to fabricate ultrafine nanoparticles (BPNP) of doxorubicin hydrochloride (DOX) for effective delivery in 4T1 cell induced breast cancer. However, adequate en...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00310
更新日期：2017-08-07 00:00:00
abstract：:Photodynamic therapy (PDT) is a light-induced chemical reaction that produces localized tissue damage for the treatment of cancers and other nonmalignant conditions. The activation of photosensitizers in a target tissue is accomplished with a specific light source in the presence of molecular oxygen. In the clinic, pa...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp100060v
更新日期：2010-08-02 00:00:00
abstract：:The interaction with cervicovaginal mucus presents the potential to impact the performance of drug nanocarriers. These systems must migrate through this biological fluid in order to deliver their drug payload to the underlying mucosal surface. We studied the ability of dapivirine-loaded polycaprolactone (PCL)-based na...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp300408m
更新日期：2012-11-05 00:00:00
abstract：:Constitutively activated signal transducer and activator of transcription-3 (STAT3) in tumor and dendritic cells (DCs) plays a critical role in tumor-induced immunosuppression. This is considered a major challenge in effective immunotherapy of cancer. Herein we describe the development of a polymeric nanocarrier for t...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp900145g
更新日期：2010-04-05 00:00:00
abstract：:The current regimen of factor IX (FIX) injection is of an episodic format, which leads to limited efficacy. A sustained release dosage form is beneficial in terms of reducing the injection frequency and improving the therapeutic effectiveness. The aim of this study was to formulate a new microsphere form of a FIX-cont...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp200133s
更新日期：2011-10-03 00:00:00
abstract：:Doxorubicin (DOX) is one of the most commonly used antineoplastic agents, but its clinical application is oftentimes coupled with severe side effects. Selective delivery of DOX to tumors via nanosized drug carrier represents an attractive approach to this problem. Previously, we developed a dual functional nanomicella...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp500389v
更新日期：2014-11-03 00:00:00
abstract：:The present work investigates the influence of electrostatic surface potential distribution of monoclonal antibodies (MAbs) on intermolecular interactions and viscosity. Electrostatic models suggest MAb-1 has a less uniform surface charge distribution than MAb-2. The patches of positive and negative potential on MAb-1...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp200566k
更新日期：2012-04-02 00:00:00
abstract：:Therapeutic efficacy of nanocarriers can be amplified by active targeting and overcoming the extracellular matrix associated barriers of tumors. The aim of the present study was to investigate the effect of oral antifibrotic agent (telmisartan) on tumor uptake and anticancer efficacy of EphA2 receptor targeted liposom...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.6b00187
更新日期：2016-06-06 00:00:00
abstract：:The safety and efficacy of anticancer antibody-drug conjugates (ADCs) depend on the selection of tumor-targeting monoclonal antibody (mAb), linker, and drug, as well as their specific chemical arrangement and linkage chemistry. In this study, we used a heterobifunctional cross-linker to conjugate docetaxel (DX) to cet...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.8b00672
更新日期：2018-11-05 00:00:00
abstract：:Targeted therapies are emerging as a preferred strategy for treatment of cancer and other diseases. To evaluate the effect of high affinity receptors on the rate and extent of tumor penetration of receptor-targeted drugs, we have characterized the kinetics of folate-rhodamine uptake by folate receptor (FR)-expressing ...
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更新日期：2009-11-01 00:00:00
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更新日期：2008-07-01 00:00:00
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更新日期：2017-11-06 00:00:00
abstract：:Dry powders from aqueous dispersions, formed by antisolvent precipitation, dissolved to form solutions with supersaturation values up to 12 in 10 min at pH 6.8 with sodium dodecyl sulfate micelles. Itraconazole/hydroxypropylmethylcellulose (HPMC) aqueous particle dispersions were salt flocculated and filtered to produ...
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更新日期：2009-03-01 00:00:00
abstract：:In order to gain molecular level understanding of drug dissolution into aqueous media, we report the first molecular dynamics (MD) simulation of a drug crystal dissolving. The simulation was performed for acetaminophen crystal Form I dissolving in 0.15 M aqueous NaCl solution at 37 °C. The 10 ns simulation revealed in...
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更新日期：2013-03-04 00:00:00
abstract：:In this work, we demonstrated that the simple substitution of the 1,2,4-triazole moiety in 5-( 4H-1,2,4-triazol-4-yl)isophthalic acid (5-TIA) by the 1 H-1,2,3-triazol-5-yl unit enables the preparation of a hydrogelator (click-TIA). In sharp contrast to 5-TIA, its isostere click-TIA undergoes self-assembly in water upo...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b01049
更新日期：2018-08-06 00:00:00
abstract：:Platinum(IV) complexes generally require reduction to reactive Pt(II) species to exert their chemotherapeutic activity. The process of reductive activation of (15)N-labeled (OC-6-43)-bis(acetato)diamminedichloridoplatinum(IV), in the presence of nicotinamide adenine dinucleotide (NADH) and horse heart cytochrome c (cy...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.6b00438
更新日期：2016-09-06 00:00:00
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更新日期：2009-05-01 00:00:00
abstract：:Progesterone receptor (PR) is a significant biomarker in diseases such as endometriosis and breast, ovarian, and uterine cancers that is associated with disease prognosis and therapeutic efficacy. While receptor status is currently determined by immunohistochemistry assays, the development of noninvasive PR imaging ag...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp200219e
更新日期：2011-08-01 00:00:00
abstract：:Powder adhesion or sticking onto punches is one of the outstanding issues in pharmaceutical tablet manufacturing. We show in this work that, at comparable particle sizes, the acesulfame potassium exhibited pronouncedly reduced propensity to punch sticking than acesulfame. Detailed analyses revealed strong correlation ...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.9b00247
更新日期：2019-06-03 00:00:00
