This technology includes the use of JTV-519 and oxidized form of JTV-519, as a novel treatment for Wolfram syndrome and other diseases associated with endoplasmic reticulum (ER). JTV-519 can prevent the leakage of ER calcium to the cytosol and abnormal activation of a pro-apoptotic enzyme, calpain 2, in cell models of Wolfram syndrome. Further, these compounds can prevent cell death in beta cell models of these diseases.

This technology includes the utility of the novel small molecule inhibitors of ALDH1A1 (RALDH1) in combination with immunotherapy for the treatment of hepatocellular carcinoma (HCC). Recently it was shown that the ALDH1A1 catalyzed production of retinoic acid (RA) in tumor cells promotes their differentiation into immunosuppressive antigen-presenting cells. Therefore, blocking RA production by tumor cells and/or blocking RA signaling in monocytes using our ALDH1A1 inhibitors can alleviate immunosuppression and engender anti-tumor immune responses.

This technology includes compounds which are selective inhibitors of anaplastic lymphoma kinases (ALK1, ALK2, ALK3 and ALK6), which inhibit these ALKs with low nanomolar potency. These compounds could be developed as a treatment of Fibrodysplasia ossificans progressiva (FOP) and other BMP-related diseases. FOP is a rare congenital disease with no current treatment options. Since the disease is driven by constitutively active ALK2, inhibition of ALK2 would be like hitting the Achilles’ heel of the disease and would potentially be an efficacious therapy for FOP patients.

This technology includes a series of novel benzene-1,4-disulfonamides that activate TRPML1 receptor. The TRPML1 receptor is a lysosomal Ca2+ channel that has been shown to be involved in controlling lysosome functions, among then the maintenance of the integrity of the plasma membrane and the modulation of autophagosome-lysosome fusion. The improved ability of the receptor to deliver Ca2+ ions to the cytosol had been correlated with its capacity to modulate autophagy and lysosome exocytosis.

This technology includes a new Zika virus NS-1 assay which was used for a compound screen. Because the NS-1 protein is synthesized only in the Zika virus replication stage, the inhibition of NS-1 protein level by compounds determined in this NS-1 assay indicates the inhibition of Zika virus replication in human cells. A total of 256 compounds have been identified as active compounds that inhibited NS-1 production in human cells that have the potential to be developed as new therapeutics for the treatment of infection with Zika virus.

This technology includes small molecule inhibitors of the cdc2-like kinase (Clk) and Dyrk kinase which can restore splicing outcomes within many dysregulated splicing events potentially reversing phenotypes associated with diseases associated with abnormal splicing. The Clks regulate the alternative splicing of microtubule-associated protein tau and are implicated in frontotemporal dementia and Parkinson's disease through the phosphorylation of splicing factors (SF).

This technology includes a variety of structures that can effectively target the c-Abl myristate binding pocket with increased potency and brain permeability. C-Abl is a ubiquitous non-receptor tyrosine kinase involved in signal transduction. In addition to its classic function in leukemia pathogenesis, c-Abl kinase is also thought to play a role in neuronal health, whereby deregulation of c-Abl could be related to early neuronal dysfunction and cytoskeletal alterations.

This technology includes compounds, pharmaceutical compositions and methods of treating or preventing neurological or psychiatric disorders for which inhibiting KCNH2-3.1 containing potassium channels provides a therapeutic effect. Polymorphisms in the KCNH2 gene have been associated with altered cognitive function and schizophrenia. The KCNH2 gene encodes the protein which forms the human ether-a-go-go related (hERG) voltage-gated potassium channel 4, 5.

This technology includes a method to facilitate identification of drug targets that can prevent SARS-related viruses from entering human cells with ACE2 receptors on the plasma membrane. Surface binding to cellular ACE2 of the SARS-CoV-2 virus is the first step of infection for the disease COVID-19. The invention allows for visualization of cell binding and entry of a “quantum dot conjugated virus spike protein” (hereafter referred to as either a ‘QD-Spike conjugate’ or a ‘pseudo-virion’) and can be used to screen libraries of drugs that prevent/inhibit this cell entry.

This technology includes a new chemical series of substituted bicyclic heteroaryl small molecules as potent bromodomain-containing protein BRD4 inhibitors used for the treatment of cancer and inflammatory diseases. The optimization led to compounds with good potency in enzymatic assay ( 100 nM) and in MV4-11 cell-based assay ( 1000 nM) as well as excellent early ADME properties. We also identified N-methyl 2 pyridone and N-methyl pyrrolopyridone are great replacements of di-methylisoxazole. This chemical series also exhibited good ADME profiles, including PK.