Abstract：
:Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described. In the discovery setting 'the rule of 5' predicts that poor absorption or permeation is more likely when there are more than 5 H-bond donors, 10 H-bond acceptors, the molecular weight (MWT) is greater than 500 and the calculated Log P (CLogP) is greater than 5 (or MlogP > 4.15). Computational methodology for the rule-based Moriguchi Log P (MLogP) calculation is described. Turbidimetric solubility measurement is described and applied to known drugs. High throughput screening (HTS) leads tend to have higher MWT and Log P and lower turbidimetric solubility than leads in the pre-HTS era. In the development setting, solubility calculations focus on exact value prediction and are difficult because of polymorphism. Recent work on linear free energy relationships and Log P approaches are critically reviewed. Useful predictions are possible in closely related analog series when coupled with experimental thermodynamic solubility measurements.
journal_name
Adv Drug Deliv Revjournal_title
Advanced drug delivery reviewsauthors
Lipinski CA,Lombardo F,Dominy BW,Feeney PJdoi
10.1016/s0169-409x(00)00129-0subject
Has Abstractpub_date
2001-03-01 00:00:00pages
3-26issue
1-3eissn
0169-409Xissn
1872-8294pii
S0169-409X(00)00129-0journal_volume
46pub_type
杂志文章,评审abstract：:The biological clock of mammals is under the control of external factors, social life and the environment, and of internal genetic factors. When the biological clock of an individual is no longer in phase with its environment, either because there is no longer any harmony (desynchronization) between the two systems (s...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2010.06.005
更新日期：2010-07-31 00:00:00
abstract：:Biodegradable nanoparticles formulated from poly (D,L-lactide-co-glycolide) (PLGA) have been extensively investigated for sustained and targeted/localized delivery of different agents including plasmid DNA, proteins and peptides and low molecular weight compounds. Research about the mechanism of intracellular uptake o...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/s0169-409x(02)00228-4
更新日期：2003-02-24 00:00:00
abstract：:Antiepileptic drugs are commonly given orally for chronic treatment of epilepsy. The treatment of epilepsy requires administration of medications for both acute and chronic treatment using multiple types of formulations. Parenteral routes are used when the oral route is unavailable or a rapid clinical response is requ...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章
doi：10.1016/j.addr.2012.01.017
更新日期：2012-07-01 00:00:00
abstract：:Current treatment of human immunodeficiency virus type-1 (HIV-1) infection involves a combination of antiretroviral drugs (ARVs) that target different stages of the HIV-1 life cycle. This strategy is commonly referred to as highly active antiretroviral therapy (HAART) or combined antiretroviral therapy (cART). Membran...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2016.05.001
更新日期：2016-08-01 00:00:00
abstract：:Toll-like receptor 9 (TLR9) agonists have demonstrated substantial potential as vaccine adjuvants, and as mono- or combination therapies for the treatment of cancer and infectious and allergic diseases. Commonly referred to as CpG oligodeoxynucleotides (ODN), TLR9 agonists directly induce the activation and maturation...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2008.12.008
更新日期：2009-03-28 00:00:00
abstract：:Two-photon excitation imaging is the least invasive optical approach to study living tissues. We have established two-photon extracellular polar-tracer (TEP) imaging with which it is possible to visualize and quantify all exocytic events in the plane of focus within secretory tissues. This technology also enables esti...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章
doi：10.1016/j.addr.2006.07.008
更新日期：2006-09-15 00:00:00
abstract：:Small interfering RNA (siRNA) that silence genes by the process of RNA interference offers a new therapeutic modality for disease treatment. Polycation-based nanoparticles termed polyplexes have been developed to maximise extracellular and intracellular siRNA delivery, a key requirement for enabling the clinical trans...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2012.07.004
更新日期：2012-12-01 00:00:00
abstract：:Mitochondria represent both the main source and target of reactive oxygen and nitrogen species (RONS). In view of the large energy expenditure made by neurons during neurotransmission, an intact mitochondrial function is of paramount importance for the correct function of the brain. Accordingly, the search of therapeu...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2009.05.009
更新日期：2009-11-30 00:00:00
abstract：:Recreating the beating heart in the laboratory continues to be a formidable bioengineering challenge. The fundamental feature of the heart is its pumping action, requiring considerable mechanical forces to compress a blood filled chamber with a defined in- and outlet. Ventricular output crucially depends on venous loa...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2015.09.001
更新日期：2016-01-15 00:00:00
abstract：:Intramammary infections (IMIs) represent a major feature in bovine pathology. The treatment of IMIs concern antimicrobial substances. Therapeutic strategies involve administration of immediate release formulations during lactation with or without long-acting formulations during the dry period. Current treatments are n...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/s0169-409x(01)00160-0
更新日期：2001-09-01 00:00:00
abstract：:The great interest in mucosal vaccine delivery arises from the fact that mucosal surfaces represent the major site of entry for many pathogens. Among other mucosal sites, nasal delivery is especially attractive for immunization, as the nasal epithelium is characterized by relatively high permeability, low enzymatic ac...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2008.09.005
更新日期：2009-02-27 00:00:00
abstract：:Antibodies can have exquisite specificity of target recognition and thus generate highly selective outcomes following their systemic administration. While antibodies can have high specificity, the doses required to treat patients, particularly for a chronic condition, are typically large. Fortunately, advances in prod...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2006.03.011
更新日期：2006-08-07 00:00:00
abstract：:Molecular imaging is an emerging technology that allows the visualization of interactions between molecular probes and biological targets. Molecules that either direct or are subject to homeostatic controls in biological systems could be labeled with the appropriate radioisotopes for the quantitative measurement of se...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2010.09.007
更新日期：2010-08-30 00:00:00
abstract：:Progress in gene therapy has produced promising results that translate experimental research into clinical treatment. Gene modification has been extensively employed in cell transplantation. The main barrier is an effective gene delivery system. Several viral vectors were utilized in end-stage differentiated cells. Re...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2007.08.039
更新日期：2008-01-14 00:00:00
abstract：:Pulmonary arterial hypertension (PAH) is a rare, but severe and life-threatening disease characterized by vasoconstriction and remodeling of the pulmonary arterioles, leading to progressive increase in pulmonary vascular resistance and ultimately to right-heart failure. In the last two decades, significant progress in...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2018.06.003
更新日期：2018-08-01 00:00:00
abstract：:Lack of approved pharmaceutical agents and/or pharmacokinetic data in the literature for exotic, wildlife, and zoo species is a major issue for veterinarians. These practitioners must take approved agents (veterinary or human) and extrapolate their use to non-approved species with little or no scientific basis to supp...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/s0169-409x(02)00068-6
更新日期：2002-10-04 00:00:00
abstract：:Type 1 diabetes is an autoimmune disease marked by the destruction of insulin-producing beta cells in the pancreatic islets. Strategies to delay onset or prevent the autoimmune recognition of beta cell antigens or T cell-mediated killing of beta cells have mainly focused on systemic immunomodulation and antigen-specif...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2017.06.007
更新日期：2017-05-15 00:00:00
abstract：:Oral delivery is the most common method for drug administration. However, poor solubility, stability, and bioavailability of many drugs make achieving therapeutic levels via the gastrointestinal (GI) tract challenging. Drug delivery must overcome numerous hurdles, including the acidic gastric environment and the conti...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2011.12.009
更新日期：2012-05-01 00:00:00
abstract：:A "microdose clinical trial" (microdosing) is one kind of early phase exploratory clinical trial, administering the compound at doses estimated to have no pharmacological or toxicological effects, aimed at screening candidates for further clinical development. This article's objective is to clarify the ethical, legal,...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2011.01.002
更新日期：2011-06-19 00:00:00
abstract：:Transferrin receptor has been an important protein for many of the advances made in understanding the intricacies of the intramolecular sorting pathways of endocytosed molecules. The unique internalization and recycling functions of transferrin receptor have also made it an attractive choice for drug targeting and del...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2003.07.004
更新日期：2003-11-14 00:00:00
abstract：:Most antifolate drugs are efficiently transported by the reduced-folate carrier (RFC). However, several also bind with high affinity to the alpha-isoform of the folate receptor (alpha-FR) and there is evidence to suggest that this transport mechanism may contribute to their activity when the receptor is highly overexp...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2004.01.003
更新日期：2004-04-29 00:00:00
abstract：:Safe and effective hemoglobin-based blood substitutes may be advantageous over conventional therapies for certain clinical settings requiring short term blood replacement such as emergency resuscitation and hemodilution in surgery. Many advances have been made in developing these oxygen therapeutics, however safety co...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/s0169-409x(99)00050-2
更新日期：2000-02-28 00:00:00
abstract：:High affinity antibodies are crucial both for the discovery and validation of biomarkers for human health and disease and as clinical diagnostic and therapeutic reagents. This review describes some of the latest technologies for the design, mutation and selection of high affinity antibodies that provide a paradigm for...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2006.01.025
更新日期：2006-08-07 00:00:00
abstract：:Prior to the introduction of troglitazone, it had been more than 30 years since the last significant improvement in antidiabetic therapy. In view of the pressing need for more effective oral agents for the treatment of Type 2 diabetes mellitus, troglitazone was granted priority review by the FDA and was launched in th...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/s0169-409x(02)00093-5
更新日期：2002-11-05 00:00:00
abstract：:Patients with critical limb ischemia constitute a potential target population for therapeutic angiogenesis. Because the growth of new collateral vessels can be achieved in a time interval of 1 month or less, these patients are suitable candidates for treatment with non-viral vectors intended to yield short-term gene e...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章
doi：10.1016/s0169-409x(97)00115-4
更新日期：1998-03-02 00:00:00
abstract：:Hepatocellular carcinoma (HCC) remains one of the most lethal forms of cancer in the world. In this arena, utilities of microRNA (miRNA) as a sophisticated tool, in therapeutics and diagnostics, remains a prime focus among the leading researchers. It is well known that viral hepatitis, chronic alcoholism and metabolic...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2014.10.029
更新日期：2015-01-01 00:00:00
abstract：:Islet transplantation has the potential to cure type 1 diabetes. Despite recent therapeutic success, it is still not common because a large number of transplanted islets get damaged by multiple challenges including instant blood mediated inflammatory reaction, hypoxia/reperfusion injury, inflammatory cytokines, and im...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2010.11.003
更新日期：2011-01-01 00:00:00
abstract：:The objective of this review is to summarize the critical steps in intracellular trafficking and the principal factors involved in transgene expression by a comparison of viral and non-viral gene vectors. Intracellular trafficking of viral and non-viral gene vectors are reviewed kinetically as well as from the mechani...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/s0169-409x(01)00216-2
更新日期：2001-11-19 00:00:00
abstract：:An essential element of tissue homeostasis is the response to injuries, cutaneous wound healing being the most studied example. In the adults, wound healing aims at quickly restoring the barrier function of the skin, leading however to scar, a dysfunctional fibrotic tissue. On the other hand, in fetuses a scarless tis...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2018.04.011
更新日期：2019-06-01 00:00:00
abstract：:A site-directed method of joining proteins to poly(ethylene glycol) is presented which allows for the preparation of essentially homogeneous PEG-protein derivatives with a single PEG chain conjugated to the amine terminus of the protein. This selectivity is achieved by conducting the reductive alkylation of proteins w...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/s0169-409x(02)00023-6
更新日期：2002-06-17 00:00:00
