Compounds that Interfere with the Androgen Receptor Complex

Investigators at the National Institutes of Health (NIH) have discovered compounds that have potential as novel anti-androgen therapeutics. The immunophilin protein FKBP52 is part of a protein complex that helps fold the androgen receptor (AR) protein, a target for treating prostate cancer, and enhances its activity. Disruption of the FKPB52-AR interaction greatly reduces the activity of the AR.

Treatment of GPR101-Related, Growth Hormone-Related Disorders Such as Gigantism, Dwarfism or Acromegaly

Microduplications of the GPR101 gene (located on chromosome Xq26.3 and encodes a G-protein coupled receptor) can result in an excess of growth hormone causing gigantism, that has an onset in early childhood. It is also associated with the growth of sporadic growth hormone producing adenomas in some patients with acromegaly.

SLCO1B3 Genotyping to Predict a Survival Prognosis of Prostate Cancer

Steroid hormones have been implicated to play a fundamental role in the pathogenesis of prostate cancer. Polymorphisms in the genes that code for enzymes, or hormones involved in androgen regulatory pathway, reportedly influence risk for developing prostate cancer. Since many membrane transporters are modulators of steroid hormones absorption and tissue distribution, genetic polymorphisms in genes encoding these transporters may account for the risk of prostate cancer and the predicting of survival.

A peptide hydrogel for use in vascular anastomosis

In collaboration with surgery specialists from Johns Hopkins University, researchers at the National Cancer Institute (NCI) developed novel hydrogel compositions and methods of using them in the microsurgical suturing of blood vessels, which is particularly beneficial for surgeons in whole tissue transplant procedures. The lead candidate electropositive hydrogels, called APC1, was demonstrated in anastomosis mice models to be well tolerated, biocompatible, and non-toxic.

Renal Selective Unsaturated Englerin Analogues

Englerin A, a natural product, has shown growth-inhibiting activity against renal cancer cell lines. The compound is an agonist of protein kinase C (PCK) theta, which results in cell cytotoxicity, insulin inhibition, and selective activation of viral replication in T cells.  Englerin A derivatives are promising treatment strategies for any diseases associated with PKC theta and/or ion channel proteins.

Aryl Hydantoin Heterocycle Compounds that Target the Androgen Receptor for Prostate Cancer Treatment

Prostate cancer is the most prevalent form of cancer among all men in the United States (US). It is also the second leading cause of cancer-related deaths in the US among men, largely due to the progressively treatment resistant nature of the disease. Treatment options for early stage prostate cancer include watchful waiting, radical prostatectomy, radiation therapy, and importantly androgen-deprivation therapy (ADT). Prostate cancer is dependent on androgen hormones, such as testosterone, for sustaining and promoting growth.

Topical Sodium Nitrate Ointment for Sickle Cell Disease

Chronic leg ulcers are a debilitating vasculopathic complication for some patients with sickle cell disease (SCD). Prevalence of leg ulcers varies based on age and geographic location; about 5-10% of all SCD patients may suffer leg ulcers. These leg ulcers are painful, result in infections, hospitalization, disability, and negatively impact the patient’s social and psychological wellbeing on an ongoing basis.

Transgenic Mice Expressing CNO-sensitive Gq- or Gs-coupled Designer Receptors Selectively in Pancreatic Beta Cells

Impaired functioning of pancreatic beta cells is a key hallmark of type 2 diabetes. Beta cell function is modulated by the actions of different classes of heterotrimeric G proteins. The functional consequences of activating specific beta cell G protein signaling pathways in vivo are not well understood at present, primarily due to the fact that beta cell G protein-coupled receptors (GPCRs) are also expressed by many other tissues.

Triazole Derivatives of 4,7-disubstituted 2 naphthoic acid (PPTN) as P2Y14 Receptor Antagonists

The Molecular Recognition Section of NIDDK announces the availability of a novel triazole-based probes, structures which act as antagonists at human P2Y14 receptors. Although the physiologic functions of this receptor remain undefined, recently it has been strongly implicated in immune and inflammatory responses. Prior work with a 4,7-disubstituted 2 naphthoic acid derivative (PPTN) established the ability to inhibit chemotaxis of human neutrophils in the lung and kidney.

Remotely Monitored Mouse Feeding Experimentation Device

How much does a mouse eat per day? If a researcher is conducting dietary studies, the answer is very important. For instance, obesity studies require accurate measures of feeding. Existing automated methods for taking feeding measurements are expensive and use specialized caging that is not compatible with typical vivarium colony racks. As a result, many researchers simply weigh food each day or two to determine how much food the mice ate. This is time-consuming, can be error prone, and provides a low temporal resolution view of feeding.