Novel Furoquinolinediones as Inhibitors of TDP2 and Their Potential Use to Treat Cancer

Tyrosyl-DNA phosphodiesterase 2 (TDP2) is an enzyme that playings a critical role in repairing nucleic acid lesions, namely by repairing trapped DNA cleavage complexes. TDP2 repairs topoisomerase (TOP2)-mediated DNA damage induced by chemotherapeutic agents and removes endogenous TOP2-DNA cleavage complexes. Further, TDP2 deficiency potentiates the antiproliferative activity of TOP2 inhibitors. This suggest that combination therapies consisting of TDP2 and TOP2 inhibitors have a synergistic effect on tumor tissues.

T-Cell Immunotherapy that Targets Aggressive Epithelial Tumors

Metastatic cancers cause up to 90% of cancer deaths, yet few treatment options exist for patients with metastatic disease. Adoptive transfer of T cells that express tumor-reactive T-cell receptors (TCRs) has been shown to mediate regression of metastatic cancers in some patients. Unfortunately, identification of antigens expressed solely by cancer cells and not normal tissues has been a major challenge for the development of T-cell based immunotherapies. Thus, it is essential to find novel target antigens differentially expressed in cancer versus normal tissues.

Thyclotide Peptide Conjugates With Cell Permeability And Inhibitory Activity

Thyclotides are oligomeric molecules with chiral tetrahydrofuran (THF) diamine units consisting of either R,R or
S,S stereochemistry. Thyclotide sequences with R,R stereochemistry bind to complementary DNA and RNA
sequences with strong affinity and sequence specificity, while thyclotides with S,S stereochemistry have a helical
handedness that does not allow binding to DNA or RNA. Thyclotides are cell permeable and can be used to
suppress microRNA activity in cells. Peptides are oligomeric molecules consisting of amino acids found in

Improved Antibodies Against ERBB4/HER4

The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Molecular Neurobiology is seeking statements of capability or interest from parties interested in collaborative research to further evaluate or commercialize specific rabbit monoclonal antibodies generated against the ErbB4 receptor (also known as HER4) that have been validated for specificity using tissue sections and extracts from ErbB4 knockout mice.

Sidechain Functionalized S-Acylbenzamides With Anti-HIV Activity

HIV infection remains a major medical problem, with approximately 38 million people worldwide living with HIV. Nipamovir and SAMT-247 are simple and inexpensive small molecules that inactivate HIV virus by interference with final maturation steps of the virus. This mechanism provides a high barrier for HIV to develop resistance. In fact, lab experiments designed to encourage HIV to develop resistance to Nipamovir and SAMT-247 have all failed. In animal tests, Nipamovir and SAMT-247 do not display toxic side effects.

Single Domain Antibodies (Nanobodies) Targeting SARS-CoV-2 for treating COVID-19

The COVID-19 pandemic is a worldwide public health crisis with over 100 million confirmed cases and 2.4 million deaths as of February 2021. COVID-19 is caused by a novel coronavirus called SARS-CoV-2. SARS-COV-2 infects hosts via its spike (S) protein. The S protein contains the receptor binding domain (RBD) that binds to the angiotensin converting enzyme 2 (ACE2) receptor on human cells to facilitate viral entry and infection. There are few therapeutics available for COVID-19 patients that directly target SARS-CoV-2.

Optical Trap Methods to Determine the Viscoelastic Properties of Biological Materials

Optical traps (optical tweezers) have a focused laser beam able to trap a small bead at its focus, and are used to measure the microrheology of gels and other materials. They have recently been used to characterize properties of living cells, however issues of image spatial resolution and limited depth of interrogation have prevented application of an optical trap to measure microrheological (flow of matter) properties in complex (non-uniform) materials, such as multi-cellular systems or living organisms. 

Nanobodies Neutralizing Lassa Virus

Lassa Hemorrhagic Fever (LHF) is a serious disease caused by infection with Lassa virus (LASV) – highly prevalent in West Africa and spreading globally. LASV is associated with high morbidity and mortality rates, annually infecting 100,000 to 300,000 individuals and causing 5,000 deaths. Developing prophylactics and treatment for LASV is difficult due to challenges in inducing neutralizing antibodies and producing their target, the LASV glycoprotein trimer (GPC).

High-Affinity Rabbit Monoclonal Antibodies for Cancer Treatment

Mesothelin is a cell surface protein that is highly expressed in aggressive cancers, such as malignant mesothelioma, ovarian cancer and pancreatic cancer, lung cancer, breast cancer, cholangiocarcinoma, bile duct carcinoma and gastric cancer.  Because of this selective expression, mesothelin is an excellent candidate for targeted therapeutics, such as monoclonal antibodies (mAbs) and chimeric molecules.  Current anti-mesothelin therapeutic mAb candidates bind to an epitope in Region I of mesothelin.  Unfortunately, Region I contains the interaction site MUC16/CA125, a mesothe