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Small Molecule Therapeutics

The Power of Small Molecules and its Potential Targets.

Many small molecules can work as therapeutic agents. Novel synthetic compounds and endogenous molecules, such as metabolites, can influence biology by modifying its availability within a cell. New and effective molecular therapeutics capitalize on these findings and are being further developed at UMassMed. In addition, there is research into identifying the critical molecular targets that may enable further discoveries of therapeutic targets.




Browse Our Small Molecule Therapeutics Inventions:




Title: Lanatoside C Inhibition of Zika Virus Infection. UMMS16-60; Patent Pending. 

  • This new discovery has found that cardiac glycoside Lanatoside C - an inhibitor of dengue virus, flavivirus Kunjin, alphavirus Chickingunya, and enterovirus 71 - also effectively stops replication of the Zika virus. This invention discloses treatment of Zika virus with Lanatoside C alone and in combination with ribavirin or ivermectin.

Title: Topical Application of Agents to Affect Neutrophil Migration Across Polarized Epithelial Barriers. UMMS16-46; Patent Pending.

  • A newly discovered efflux pump, MRP2, secretes lipids that attract neutrophils and initiate inflammation. Inhibition of MRP2 or inactivation of the secreted lipids can safely and effectively reduce inflammation at local tissues. This invention reduces inflammation by opposing the pro-inflammatory MRP2 system also by utilizing an endocannabinoid system that acts through the CB2 receptor. Increasing the activity of the CB2 endocannabinoid pathway can suppress local neutrophil migration consequentially result in anti-inflammation.

Title: Anthelmintic Compositions and Methods. UMMS16-43; Patent Pending. 

  • This technology is based on the novel discovery that crystal proteins are highly potent anthelmintics. The invention comprises compositions and methods to treat a parasitic worm infection by administering to a subject a recombinant gram-positive bacterium expressing a crystal protein. The invention further discloses combination therapies wherein the recombinant bacteria is combined with a nicotinic acetylcholine receptor agonist.

Title: A New Generation of Antihelminthic Medications that Trigger Aberrant Immune Responses in Pathogenic Nematodes. UMMS16-25; Patent Pending. 

  • The present invention is related to the treatment and prevention of nematode infection in mammals. In general, the present invention provides small organic compounds and RNAi molecules targeting the p38 mitogen activated protein kinase pathway in xenobiotic-resistant nematodes. Further, the present invention combines an immunostimulatory small molecule with a pharmacologic inducer of an endoplasmic reticulum unfolded protein response to provide a synergistic therapy for human pathogenic nematode infection.

Title: Identification of Epigenetic Modifiers of the Silenced FMR1 Gene: Potential Targets for Fragile X Syndrome Therapeutics. UMMS16-03; Patent Pending.  

Title: Improving Efficacy of VEGF-Targeted Therapy in Prostate Cancer. UMMS16-02; Patent Pending. 

  • This invention discloses methods to improve the response to VEGF/VEGFR-targeted therapy in patients resistant to bevacizumab and sunitinib. Our critical finding is that inhibition of Rac1 activity using a commercially available compound renders resistant cells sensitive to bevacizumab and sunitinib and can therefore be used as an adjuvant to treat aggressive forms of prostate cancer.

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Title: New XCI Inhibitors as Potential Rett Syndrome Therapeutics. UMMS15-53; Patent Pending.

Title: Targeting GDF6 and BMP Signaling for Anti-cancer Therapy. UMMS15-21; Patent Pending. 

  • A method of treating a melanoma in a subject, comprising administering to a subject an effective amount of an inhibitor of GDF6/BMP13 activity.

Title: Hedgehog Signaling in Bipolar Affective Disorder. UMMS15-02; Patent Pending. Related Publication

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  • Invention encompasses a new strategy to combat drug-resistant gonorrhea. This technology manipulates the lipooligosacchride capping of gonococci, thereby decreasing it’s fitness and virulence. By interrupting the sialic acid mediated pathogenesis that contributes to drug-resistance, this intervention can render gonorrhoeae sensitive to killing by the innate immunity system.

Title: A Method to Treat Chronic Myelogenous Leukemia (CML) Patients who have Developed BCR-ABL-Independent Imatinib Resistance and to Eradicate CML Stem Cells. UMMS14-47; Patent Pending.

  • This new innovation addresses the issues associated drug resistance of chronic myeloid leukiemia (CML) cells to imatinib mesylate (IM). IM improves patient survival and are used widely to treat early stages of CML, but the efficacy is known to drop when drug resistance is developed. This new invention builds on the finding that in IM resistant CML cells, RAF/MEK/ERK pathway is activated that is not subjected to IM targeting. Remarkably, when FDA approved MEK inhibitor, trametinib is treated in conjunction with IM, they synergistically kill CML cells and improve survival in mouse models.

Title: Surface Mineralization of Metal Alloys Grafted With Zwitterionic Polymer Brushes. UMMS14-36; Patent Pending. 

  • The invention provides a novel approach to hydrogels with predictable degradation/gelling kinetics, which is useful for many biomedical applications where appropriate gelling kinetics and the timely disintegration of the hydrogel (e.g., drug delivery, guided tissue regeneration) is required. Precisely controlling hydrogel degradation over a broad range in a predictable manner is achieved via a simple but versatile hydrogel platform that allows formulation of hydrogels with predictable disintegration time from within 2 days to >250 days yet comparable macroscopic physical properties.

Title: Alkylated Amphiphilic Polymer Networks for Bioactive Lipid Delivery. UMMS14-16; Patent Pending. 

  • The invention provides unique amphiphilic polymers may be employed as controlled delivery vehicles or tissue engineering scaffolds wherein the delivery of lipophilic or amphiphilic bioactive molecules can be achieved. An amphiphilic biodegradable polymer platform is disclosed herein for the stable encapsulation and sustained release of biomolecules, such as phospholipid spingosine 1-phosphate (SIP) which can be used to promote angiogenesis alone or in conjunction with VEGF.

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Title: Compositions and Methods for Recruitment and Activation of Macrophages in Injured Tissues and in Implanted Biomaterials Used for Tissue Engineering. UMMS13-62; Patent Pending. 

  • The present invention is related to the field of wound healing and regeneration and repair of injured internal tissues and tissue engineering by synthetic implants and implants of natural origin. In particular, the present invention provides compositions and methods comprising molecules (such as nanoparticles) with linked α-gal epitopes for induction of an inflammatory response localized within or surrounding damaged tissue, and rapid localized recruitment and activation of macrophages that promote regeneration and repair of a wide variety of internal tissues and organs injured as a result of various types of trauma as well as of tissues and organs treated with biomaterials.

Title: Construction of a Trifunctional and Completely Clearable Specific Targeting Agent. UMMS13-45; Patent Pending.

  • This invention provides a novel targeted delivery vehicle designed for enhanced clearing efficiency and reduced non-specific background. The invention discloses a unique pretargeting approach involving a trifunctional targeting construct and related compositions and methods that are useful in therapeutics and diagnosis (including imaging) of various biological and/or pathological conditions and diseases. The trifunctional targeting construct of the invention enables a much enhanced clearing mechanism and significantly reduced non-specific background via the completely clearable antibody construct.

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Title: Modulation of Ubiquitination of Synaptic Proteins for the Treatment of Neurodegenerative and Psychiatric Disorders. UMMS11-03; Patent Pending. 

  • This invention is a potential therapeutic for neurological and psychiatric disorders in which increased cell surface expression of AMPA, NMDA, and D1 dopamine receptors is desired. This technology is based on the discovery that inhibition of PSD-95, Mdm2, or Mdm4 decreases endocytosis of glutamate, NMDA, and dopamine receptors thereby modulating synaptic plasticity. The invention further provides screens for additional therapeutic agents targeting Mdm2, Mdm4, and PSD-95.

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Title: Arylthiazolyl Piperidines as Modulators of Survival Motor Neuron (SMN) Production. UMMS10-63; Patent Pending. 

  • This invention discloses aryl substituted thiazol-2-yl-piperidines and other related compounds that modulate production of the protein, Survival Motor Neuron (SMN), that plays a role in the treatment of spinal muscular atrophy. These newly identified compounds can modulate SMN2 protein levels and ultimately increase motor neuron survival. Pharmacological composition and methods for treating spinal muscular atrophy are further shown.

Title: SULFONATE COMPOUNDS. UMMS10-48; Patent 9,329,185.

  • This invention provides a new chemically-stable platform for delivering hydrophobic molecules in to cell cytoplasm. Sulfonates are used to impart water-solubility to hydrophobic molecules but does not readily cross cellular membrane to access cellular compartments. Thus, the TFA-labile sulfonate protection group helps to overcome the difficulty in delivering hydrophobic molecules to the intracellular environment. Currently existing protection molecules are complicated and expensive to produce while it also requires additional steps to remove its byproducts after TFA mediated deprotection. This new invention TFMB sulfonate esters are unique because they are 1) stable to nucleophilic attack (e.g. sodium iodide and piperidine), 2) synthesized in one step from commercially-available materials, and 3) easily removable with pig liver esterase (~2min). This new UMass Medical School sulfate protection group provides new opportunities for research molecule delivery of hydrophobic drugs to mammalian cells.

Title: A New Approach to Accelerate Antibiotic Action. UMMS10-30; Patent Pending.

  • This is a novel method to increase the efficacy of antibiotics by targeting bacterial central metabolism. The UMass Medical School inventors identified 38 metabolic targets, inhibition of which with concurrent antibiotic treatment can synergistically kill slow-growing dormant Mycobacterium tuberculosis (Mtb), the agent of human tuberculosis. These slow-growing bacterial populations are challenging to eradicate because they are refractory to antibiotic treatment. Inhibiting Mtb central metabolism enables more thorough treatment of tuberculosis infection and may be applicable to other infectious diseases.


  • The present invention improves upon previously described yeast-based microencapsulation methodologies, in particular, by providing for the incorporation of nanoparticles into and/or onto yeast cell wall particles (YCWPs), for example, yeast glucan particles (microparticles) (YGPs). The improved technologies provide for delivery of nanoparticles, the nanoparticles themselves having utility in biomedical applications, or the nanoparticles imparting one or more functionalities of use in various biomedical, e.g., drug delivery applications. 


  • This patented technology discloses pharmaceutical compositions consisting of L-argnine, tetrahydrobiopterin, and ascorbate to treat diseases of oxidative stress and improve the therapeutic properties of stem cells. 


  • Described are methods for treating glioblastoma by administering an inhibitor of Notch signalling, e.g., a gamma secretase inhibitor, in combination with a chemotherapeutic agent. Specifically provided are methods of administering to the subject a therapeutically effective amount of temozolomide and a gamma secretase inhibitor.

Title: Immunotherapy for T Cell-Mediated Autoimmune Diseases Using ITK Inhibitors. UMMS10-05; Patent Pending. 

  • The present disclosure is based, in part, on the discovery that interleukin-2-inducible T cell kinase (ITK) and CD28 signals regulate auto-reactive T cell trafficking and that organ-specific T cell mediated autoimmune diseases such as Type 1 diabetes and multiple sclerosis. Accordingly, the present specification provides methods of treating organ-specific T cell mediated autoimmune diseases by inhibiting ITK with a therapeutically effective amount of an ITK inhibitor, e.g., BMS509744, ibrutinib, 10n, 2-amino-5-(thioaryl)thiazole, 5 aminomethylbenzimidazole, 2-amino-5-[(thiomethyparyl]thiazole, and biaryl thiophene.

Title: Gamitrinibs Sensitize Cancer Cells to TRAIL-Mediated Cell Death. UMMS10-01; Patent Pending. 

  • This novel technology describes methods to enhance apoptosis via mitochondria-targeted anti-tumor agents, death receptor agonists, autophagy inhibitors, and NF-κB signaling pathway inhibitors, and methods of making and using the same for the treatment of disorders associated with unwanted cell proliferation.

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Title: Identification of Genes Preferentially Required for Growth of p53-Deficient Human Cancer Cells. UMMS09-56; Patent Pending. 

  • This invention discloses a novel cluster of genes discovered through a RNAi screen which could be a potential target of cancer treatment in p53 mutation cancers. p53 gene is mutated in numerous cancer therefore the newly discovered genes have potential for becoming a therapeutic target in wide range of cancers. The inventors performed a bias screen using p53 mutant cancer cells, p53-/- and +/- colorectal HCT116 cell lines and shRNA library. This screening yielded a selection of genes that are preferentially required for viability in p53 mutant cancer cells.  The verification experiments showed that a 24 gene-knockdown preferentially impaired growth of the p53 cell line. Using mice xenograft, 4 required genes were identified and show high potential for clinical use.

Title: COMPOUNDS FOR MODULATING TLR2. UMMS09-52 Patent 8,609,6639,271,972. 


  • This patented invention discloses small molecules that modulate the RNA binding protein, MEX5 to treat parasitic diseases.



  • This invention discloses an assay method for detecting anti-Neisseria antibodies. Human factor H (fH) is a virulence factor that helps Neisseria to resist complement-mediated killing, thus circumventing the host’s innate immune response. Higher serum fH levels may correlate to patient susceptibility to infection. Neisserial factor H binding protein (fHBp) can be hindered by a human amino acid sequence revealed in the present technology, to facilitate accurate detection of Neisseria that exceeds the capability of existing methods. A reaction mixture containing bactericidal anti-Neisseria antibodies, a fH polypeptide comprising an amino acid sequence of human Short Consensus Repeat 6 sources of non human complement (SCR), and a Neisseria bacterium. This invention additionally discloses an animal model of Neisseria infection.

Title: INTRACELLULAR DNA RECEPTORUMMS09-11; Patent 8,334,101.

  • The innate immune system recognizes non-self genetic material and mounts a defensive immune response. However, self cytosolic DNA at times gets targeted and the process by which this phenomenon occurs has been largely unknown. The inventors have discovered PISA (PYHIN protein stimulating ASC), a receptor found to be necessary for activation of the ACS/caspase-1 axis of innate immunity in response to recognition of self cytosolic DNA. This invention discloses methods for identification and compounds found to modulate the PISA receptor and it’s downstream immune response.


  • This invention reports the discovery of serum IgG of different individuals that block antibody (Ab) activity targeted against Neisseria membrane lipoprotein H.8. Blocking Ab activity may predispose such individuals to developing invasive disease with N. meningtitidis or decrease the efficacy of vaccines. This finding can explain the variability between individual susceptibility and provide new avenue for treatment and increasing efficacy of existing treatments.


  • This invention discloses a sequence of efficient cleavage point of F protein, of the respiratory syncytial virus (RSV) that causes infection. The cDNA has an optimized codon of F protein, which may be useful for developing a more effective RSV vaccine.


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Title: Co-evolved Protease Substrate Cleavage Site Mutations Enhance Protease Inhibitor Resistance. UMMS08-59; Patent Pending. 

  • This new invention predicates on the finding that drug resistance in HIV arises from evolution of HIV proteases and it’s associated substrates, and discloses mutation patterns of both proteases and substrates that can be used to predict the efficacy of particular therapy in HIV patients. Understanding these mutational combinations will greatly change the approach to optimizing a patient-centered approach to managing HIV therapy.

Title: Kratom and its Alkaloidal Components as Therapy for Withdrawal from Prescription Opioid Pharmaceuticals. UMMS08-53; Patent Pending. 

  • This invention utilizes natural products derived from Kratom, a medicinal herb native to Thailand, to treat opioid withdrawal from prescription opioid agents. Mitragynine is the predominant alkaloid isolated from Kratom and has been found to bind to opioid receptors. This finding suggests a mechanism by which Kratom and its derived molecules may reduce opioid craving. These findings introduce a novel potential for the development of a naturally derived agent for the treatment and management of opioid addiction and withdrawal.

Title: Use of Cathepsin B Inhibitors for the Treatment of IL-1 Related Diseases. UMMS08-51; Patent Pending. 

  • This innovation describes detailed mechanisms of how immune cells recognize microorganisms (non-self) from host (self). The cytoplasmic receptor complex NALP3 inflammasome has been found to react to a variety of crystals such as silica crystals or cholesterol crystals, all of which were found to require phagocytosis for activation. By inhibiting phagosomal acidification, the inventors were able to prevent activation of NALP3 in the presence of the crystal activators. Understanding these mechanisms may be valuable to research into IL-1 related diseases of sterile inflammation including atherlosclerosis, amyloidosis, Alzheimer silicosis, asbestosis and others. 

Title: HIV-1 Protease Inhibitors: Part 6. UMMS08-41. 

  • This invention provides new therapeutic agents to treat HIV using protease inhibitors that are less prone to resistance stemming from drug resistant mutations. Using computational and organic chemistry techniques, the inventors designed these new molecules by carefully considering nature of the HIV protease and it’s ability to detect substrates. This invention contains several sets of HIV protease inhibitors and unique drug combinations that have not yet been previously tested. 

Title: WFS1: A Master Negative Regulator of Endoplasmic Reticulum Stress Signaling and an Effective Inducer of Insulin-Producing Cells. UMMS08-40; Patent Pending.

  • This new discovery provides a potential therapeutic target for type 1 and 2 diabetes. WFS1 has been identified as a master regulator of the endoplasmic reticulum (ER) stress response pathway and helps maintain ER homeostatsis and consequently protection of beta cell insulin production. High levels of ER stress have been associated with premature death of pancreatic cells. Lentivirus-mediated WFS1 introduction has been developed to convert exocrine cells into insulin-producing cells in patients with type 1 and 2 diabetes. This innovation application may also prove to be beneficial to other diseases that arise from ER including neurodegenerative diseases.


  • This new invention predicates on the finding that midbody (MB), a singular organelle formed between daughter cells during cytokinesis required for separation, are inherited asymeetrically by daughter cell of stem cells and cancer ‘stem cells’. The new methods disclosed in this invention can modulate degradation.

Title: Use of TRAIL Protein as Antiviral Agent. UMMS08-01; Patent Pending. 

  • This new invention discloses an antiviral molecule, TRAIL, which reduces cellular antiviral effects, and may provide an opportunity for treatment of RNA virus infection.  Blocking of TRAIL significantly reduces cellular antiviral effects, thus the invention proposes the use of TRAIL as therapy to reduce viral burden.