Current Approaches and Strategies Applied in First-in-class Drug Discovery.

First-in-class drug discovery (FICDD) offers novel therapies, new biological targets and mechanisms of action (MOAs) toward targeting various diseases and provides opportunities to understand unexplored biology and to target unmet diseases. Current screening approaches followed in FICDD for discovery of hit and lead molecules can be broadly categorized and discussed under phenotypic drug discovery (PDD) and target-based drug discovery (TBDD). Each category has been further classified and described with suitable examples from the literature outlining the current trends in screening approaches applied in small molecule drug discovery (SMDD).

Acquired cystic disease associated renal cell carcinoma: A clinicopathologic and molecular study of 31 tumors.

Acquired cystic disease associated renal cell carcinomas (ACD-RCC) are rare and their molecular and histopathological characteristics are still being explored. We therefore investigated the clinicopathologic and molecular characteristics of 31 tumors. The patients were predominantly male (n = 30), with tumors mainly left-sided (n = 17), unifocal (n = 19), and unilateral (n = 29) and a mean tumor size of 25 mm (range, 3-65 mm).

HIV-1 Escape from Small-Molecule Antagonism of Vif.

The HIV-1 accessory protein Vif, which counteracts the antiviral action of the DNA-editing cytidine deaminase APOBEC3G (A3G), is an attractive and yet unexploited therapeutic target. Vif reduces the virion incorporation of A3G by targeting the restriction factor for proteasomal degradation in the virus-producing cell. Compounds that inhibit Vif-mediated degradation of A3G in cells targeted by HIV-1 would represent a novel antiviral therapeutic.

Testicular cancer: The usage of central review for pathology diagnosis of orchiectomy specimens.

Background: Radical orchiectomy specimens present a unique set of challenges for pathology assessment owing to their rarity and complexity. This study compares second opinion pathology reports generated at a single, large academic institution to primary reports from outside hospitals.

Methods: A database search was conducted for orchiectomy cases that were sent to our institution for management of testicular cancer from 2014 to 2015.

Development of new NIR-spectroscopy method combined with multivariate analysis for detection of adulteration in camel milk with goat milk.

New NIR spectroscopy combined with multivariate analysis for detection and quantification of camel milk adulteration with goat milk was investigated. Camel milk samples were collected from Aldhahira and Sharqia regions of Sultanate of Oman and were measured using NIR spectroscopy in absorption mode in the wavelength range from 700 to 2500nm, at 2cm resolution and using a 0.2mm path length CaF sealed cell.

1,2,3-Triazoles as Amide Bioisosteres: Discovery of a New Class of Potent HIV-1 Vif Antagonists.

RN-18 based viral infectivity factor (Vif), Vif antagonists reduce viral infectivity by rescuing APOBEC3G (A3G) expression and enhancing A3G-dependent Vif degradation. Replacement of amide functionality in RN-18 (IC50 = 6 μM) by isosteric heterocycles resulted in the discovery of a 1,2,3-trizole, 1d (IC50 = 1.2 μM).

Handling and reporting of orchidectomy specimens with testicular cancer: areas of consensus and variation among 25 experts and 225 European pathologists.

Aims: The handling and reporting of testicular tumours is difficult due to their rarity.

Methods And Results: A survey developed by the European Network of Uro-Pathology (ENUP) and sent to its members and experts to assess the evaluation of testicular germ cell tumours. Twenty-five experts and 225 ENUP members replied.

SAR and Lead Optimization of an HIV-1 Vif-APOBEC3G Axis Inhibitor.

We describe structure-activity relationship and optimization studies of RN-18, an HIV-1 Vif-APOBEC3G axis inhibitor. Targeted modifications of RN-18 ring-C, ring-B, ring-A, bridge A-B, and bridge B-C were performed to identify the crucial structural features, which generated new inhibitors with similar ( and ) and improved (, , and ) activities. Two potent water-soluble RN-18 analogues, and are also disclosed, and we describe the results of pharmacological studies with compound The findings described here will be useful in the development of more potent Vif inhibitors and in the design of probes to identify the target protein of RN-18 and its analogues.

Aggressive angiomyxoma of male genital region. Report of 4 cases with immunohistochemical evaluation including hormone receptor status.

Aggressive angiomyxoma (AA), first described by Steeper and Rosai (Am J SurgPathol. 1983;7:463-475), is a rare locally infiltrative tumor that usually arises in the pelvic and perineal soft tissues of young women. Approximately 150 cases have been reported in women.