PSMA-targeted small-molecule drug-conjugates with valine-citrulline and phosphoramidate cleavable linkers.

In this study, we present a modular synthesis and evaluation of two prostate-specific membrane antigen (PSMA) targeted small molecule drug conjugates (SMDCs) incorporating the potent chemotherapeutic agent monomethyl auristatin E (MMAE). These SMDCs are distinguished by their cleavable linker modules: one utilizing the widely known valine-citrulline linker, susceptible to cleavage by cathepsin B, and the other featuring a novel acid-labile phosphoramidate-based (PhosAm) linker. Both SMDCs maintained nanomolar affinity to PSMA.

Phosphorus containing analogues of SAHA as inhibitors of HDACs.

Histone deacetylases (HDACs) are a family of enzymes responsible for regulating DNA transcription by modulating its binding to histone proteins. HDACs are overexpressed in several types of cancers and are recognised as drug targets. Vorinostat, or suberanilohydroxamic acid (SAHA), is an histone deacetylase (HDAC) inhibitor with a hydroxamic acid as a zinc-binding group (ZBG), and it has been FDA approved for the treatment of T-cell lymphoma.

Corrigendum to "A click-ready pH-triggered phosphoramidate-based linker for controlled release of monomethyl auristatin E" [Tetrahedron Lett. Volume 61, Issue 41, 8 October 2020, 152398].

[This corrects the article PMC7665082.].

A click-ready pH-triggered phosphoramidate-based linker for controlled release of monomethyl auristatin E.

In this work, we developed a novel "click"-ready pH-cleavable phosphoramidate linker for controlled-release of monomethyl auristantin E (MMAE) in antibody- and small molecule-drug conjugates application. This water-soluble linker was found to have tremendous stability at physiological pHs while rapidly releasing its payload at acidic pH. The linker can also be tailored to release payloads of diverse functional groups, broadening its applications.

Phosphoramidate derivates as controlled-release prodrugs of l-Dopa.

l-Dopa has continued to be a mainstay in the symptomatic treatment of Parkinson's disease (PD). However, extensive peripheral metabolism, a short systemic circulation half-life and development of motor complications called dyskinesia prevents its long-term utilization as a PD therapeutic. Herein, we report a series of phosphoramidate derivatives of l-Dopa and controlled release of l-Dopa at pH 7.

Selected aspects of the epidemiology of psychoses in Croatia, Yugoslavia. IV. Representative sample of Croatia and results of the survey.

This is the fourth paper in a series on the epidemiology of psychoses in Croatia, Yugoslavia. Data collected from 1960-1975 on a representative sample of the population of the study area, including the Istrian Peninsula and the northern Adriatic littoral, and the control area, the rest of Croatia, indicate that functional psychotic illnesses are more frequent in the study area, with the highest rates in older population groups. The finding is not associated with coastal or inland residence, with educational level, or with occupational group.

Design and methodology of the Zagreb preliminary study: response rates at the study stages.

A procedure for recruitment of a trial cohort from a demographically defined population is described. Provision was made by means of a prescreening survey to determine demographic and attitudinal characteristics in the group invited to screening before the invitation was extended, thus providing information on non-participants as well as participants. Men who satisfied the criteria for borderline levels of one or more of the three risk factors on at least two of possible three occasions were invited to participate in a radomized multifactor treatment trial either being treated by medication for the appropriate risk factor [or factors], or observed during the same intervals in the same fashion as those treated.

Effect of repetitive health examinations on blood sugar levels: the Zagreb preliminary study.

In this study recruitment rates of subjects with borderline glucose tolerance were investigated (using the specific procedure described below) and were shown to be 1.8% of the population approached and 2.5% of the population screened.

Repetitive health examinations as an intervention measure.

A cohort of 107 men aged 51-53 years with borderline levels of blood pressure, serum cholesterol, or glucose tolerance was recruited from a general population in central Zagreb, Yugoslavia, and randomized into two groups; one was treated with drugs and the other observed in a similar fashion but not treated. Ninety-five men appeared regularly for the check-ups over a 2-year period. Levels of systolic blood pressure, cholesterol, and glucose showed a substantial decrease over a period of 2 years in both treated and control groups.