Organic Chemistry Commons^™

Reversible, Light-Controlled Inhibition Of Stim1-Mediated Calcium Signaling Using Photoswitchable Ml-9 Derivatives In Jurkat-Lucia Nfat Reporter T Cells, José L. Matute Gálvez

Honors Scholar Theses

Store-operated calcium entry (SOCE) through calcium release-activated

calcium (CRAC) channels is the dominant pathway for sustained Ca2+ influx in

non-excitable cells and is essential for T cell activation, driving downstream

signaling through the calcineurin-NFAT transcriptional axis. Dysregulation of

SOCE produces multi-systemic disease phenotypes, establishing that precise,

spatiotemporally controlled modulation of this pathway is a fundamental

therapeutic requirement. ML-9 is one of the only characterized small molecules

capable of targeting SOCE upstream at the level of STIM1 localization, but lacks

the selectivity, pharmacokinetic properties, and spatiotemporal control necessary

for therapeutic development.

This work describes the design, synthesis, and biological evaluation of …

Synthesis And Characterization Of Succinate Dehydrogenase Inhibitors H2/Z14 And C6/Z96 In Order To Combat Small Cell Lung Cancer, Lauren M. Graves

Honors Undergraduate Theses

The use of ubiquinone inhibitors to combat cancer is a recent development in medicinal science and procedures to efficiently synthesize these drugs remain limited. C6/Z96 and H2/Z14, two succinate dehydrogenase inhibitors, have been previously tested in vitro against NSCLC with positive results. Their similarity to ubiquinone is what makes them a strong candidate for a succinate dehydrogenase inhibitor at the ubiquinone binding site. The heterocyclic scaffolds and substituents are proposed to bind strongly through a combination of electronics, hydrogen-bonding, and fit, allowing them to bind well and prove to be more favorable than ubiquinone when competing for the Q-site. By …

Design, Syntheses And Biological Applications Of Fluorescent Probes For Nad(P)H, Hsa And Cellular Microenvironment Sensing, Adenike M. Olowolagba

Dissertations, Master's Theses and Master's Reports

Fluorescent probes have emerged as powerful tools for investigating complex biological processes due to their high sensitivity, selectivity, and capability for real-time, non-invasive imaging. In particular, the detection of key biomolecules such as NAD(P)H, viscosity-related parameters, human serum albumin (HSA), and pH is essential for understanding cellular metabolism, redox homeostasis, and disease progression. In Chapter 2, three coumarin-based fluorescent probes (A–C) were designed, synthesized, and characterized for monitoring NAD(P)H levels in living cells. Probes A and B feature coumarin–cyanine hybrid structures linked via vinyl and thiophene bridges to 3-quinolinium acceptors, respectively, while probe C incorporates a dicyano moiety to replace …

Determination Of Structural Factors Contributing To Protection Of Zinc Fingers In Estrogen Receptor Α Through Molecular Dynamic Simulations, Patricia B. Lutz, Wesley R. Coombs, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

The ERα transcription factor that induces tumor growth is a potential target for breast cancer treatment. Each monomer of the ERα DNA-binding domain (ERαDBD) homodimer has two conserved (Cys)₄-type zinc fingers, ZF1 (N-terminal) and ZF2 (C-terminal). Electrophilic agents release Zn²⁺ by oxidizing the coordinating Cys of the more labile ZF2 to inhibit dimerization and DNA binding. Microsecond-length molecular dynamics (MD) simulations show that greater flexibility of ZF2 in the ERαDBD monomer leaves its Cys more solvent accessible and less shielded from electrophilic attack by sulfur-centered hydrogen bonds than ZF1 which is buried in the protein. In the …

Killing Cancer: Manipulating Hydrophobic Vanadium Complexes To Improve Anti-Cancer Activity, Levi Ausherman, Debbie C. Crans, Peter A. Lay, Maggi Braasch-Turi

SACAD: Scholarly Activities

Hydrophobic vanadium complexes have recently shown improved anti-cancer activities compared to cisplatin. The hydrophobicity and anti-proliferative activity of [VO(Hshed)(dtb)] ([Hshed= N-(salicylideneaminato)-N’-(2-hydroxyethyl)-1,2-ethanediamine and dtb= 3,5-di(tert-butyl)catechol)]) have inspired the development of a library of hydrophobic vanadium complexes. Increasing the steric bulk of the catechol ligand has been shown to have a direct impact on hydrophobicity and anti-proliferative activities. Currently at Fort Hays State University, the Braasch-Turi group is synthesizing VO(HSHED)(dtb) to build up material to support the chemical analysis and biological assay performed by our collaborators at Colorado State University and the University of Sydney, Australia, respectively. In the future, we plan …

Synthesis Of Novel 5-Aryl 2’-Deoxyuridine And 2’-Deoxycytidine Analogues, Kevin E. Persaud

Dissertations and Theses

Briefly, the following report details a synthetic route to prepare 5-phenyl-2’-deoxycytidine analogues. This multistep synthesis began with silyl protection of the 3’- and 5’-hydroxyl groups of 5-iodo-2’-deoxyuridine. Next, the installation of a phenyl ring at the C5 position of the nucleobase via a Suzuki-Miyaura cross-coupling reaction, yielding 5-phenyl-2’-deoxyuridine (5-PdU). After that, modification of the obtained 5-PdU at the C4 position was performed with benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP, a peptide-coupling agent) and a base (cesium carbonate) to activate the amide group of the uridine nucleobase for subsequent displacement with a variety of amines. Modification of the C4 position resulted in protected 5-phenyl-2’-deoxycytidine …

Synthesis Of Long Oligodeoxynucleotides, Yipeng Yin

Dissertations, Master's Theses and Master's Reports

Synthetic long oligodeoxynucleotides (ODNs) have found wide applications in diverse fields such as chemical biology, synthetic biology, and genes and genomes synthesis. Those applications leading to a significant demand for their production. However, traditional methods for purifying synthetic ODNs present notable drawbacks, particularly their inability to purify long ODNs, rendering long ODN synthesis challenging. To address these issues, chemical synthesis techniques for long ODNs coupled with non-chromatographic purification methods have been developed. This technology makes the purification of long synthetic ODNs feasible and offers a viable pathway for producing genes and genomes with extensive repeats or stable secondary structures, which …

Development And Biological Evaluation Of Selective Small-Molecule Inhibitors Of The Human Cytochrome P450 1b1, Austin Hachey

Theses and Dissertations--Chemistry

The human cytochrome P450 1B1 (CYP1B1) is an emerging target for small- molecule therapeutics. Several solid tumors overexpress CYP1B1 to the degree that it has been referred to as a universal tumor antigen. Conversely, its expression is low in healthy tissues. CYP1B1 may drive tumorigenesis through promoting the formation of reactive toxins from environmental pollutants or from endogenous hormone substrates. Additionally, the expression of CYP1B1 in tumors is associated with resistance to several common chemotherapies and with poor prognoses in cancer patients. However, inhibiting CYP1B1 with small molecules has been demonstrated in cellular and murine model systems to reverse this …

Telp Theory: Elucidating The Major Observations Of Rieger Et Al. 2021 In Mitochondria, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

The transmembrane-electrostatically localized protons (TELP) theory may represent a complementary development to Mitchell's chemiosmotic theory. The combination of the two together can now excellently explain the energetics in mitochondria. Our calculated transmembrane-attractive force between an excess proton and an excess hydroxide explains how TELP may stay within a 1-nm thin layer at the liquid-membrane interface. Consequently, any pH sensor (sEcGFP) located at least 2–3 nm away from the membrane surface will not be able to see TELP. This feature as predicted from the TELP model was observed exactly in the experiment of Rieger et al., 2021. In contrast to their …

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …

A Study On Interactions Between Metal-Organic Frameworks And Biological Materials, Josh Phipps

Graduate Theses and Dissertations

Metal-organic frameworks or MOFs are an extremely useful tool in many areas of applications. Their popularity in recent years has arisen from their high efficiency in catalytic chemical reactions. This is made possible due to their porous interior and the ability of the MOFs components to be functionalized. These same traits make MOFs excellent for use in protein encapsulation or immobilization and have the potential to become excellent drug carriers. Their development in this utilization has been limited dramatically compared to MOFs chemical applications. This is due in part to the nature of biological processes taking longer to study, but …

Ferrocenium Salt Aided Substitution Reactions And Synthesis Of Glycosylated Curcumin Derivatives, Deva Saroja Talasila

Dissertations

Organic synthesis has been significantly advanced with the employment of transition metal complexes. The discovery of transition metal catalysts provided the synthetic community with powerful tools for accelerating reactions and making them more selective and efficient. Many chemical reactions do not happen without a catalyst.

Iron-based catalysts have several advantages for the chemical industry because it is a non-toxic and ecologically friendly metal. Our group previously found that ferrocenium cations with a 3+ oxidation state of iron-catalyzed propargylic substitution reactions at low temperatures. The sandwich structure of ferrocenes allows substituents to be introduced on the cyclopentadienyl rings, which allows for …

Effects Of Dibutyltin Exposures On Translation Regulatory Factor S6 In Human Immune Cells, Meaghan Lewis, Amanda Ruff, Margaret Whalen

Student Research

Dibutyltin is an organotin contaminating the environment through its use as a stabilizer in polyvinylchloride, PVC plastics. DBT has been found in drinking water and beverages, such as beer and wine, due to leaching from the PVC plastics used during the distribution of these drinks. Along with PVC plastics, DBT has been used as a deworming agent in poultry, infiltrating additional food products and increasing the exposure of the toxin to humans. Due to its multiple uses, it has entered the food chain and has been detected in human blood at levels as high as 0.3μM. Inflammatory cytokines are important …

Antimicrobial Activity Of Bacterial Virus Components: An Empirical Investigation Of The Killing Capacity Of Toxins From Burkholderia, Kyle Walny

Honors Projects

Given the growing issue in healthcare of antibiotic resistance, effective and safe alternative treatment methods are required. One of these possible alternative treatment methods is bacteriotoxins including bacteriocins and tailocins. The focus of this study is a bacteriotoxin from Burkholderia cenocepacia (ATCC 25608), which was induced for toxin using a modified UV light induction procedure and tested against a variety of Pseudomonas and Burkholderia for its killing capacity. Various other pathogenic strains were then induced with UV light and tested. The results showed that the toxin from ATCC 25608 was very effective against most of the Burkholderia tested and warrants …

Engineering Fluorescently Labeled Human Fibroblast Growth Factor One Mutants And Characterizing Their Photophysics Properties Towards Designing Fret Assays, Mamello Mohale

Graduate Theses and Dissertations

Human fibroblast growth factor one (hFGF1) belongs to a family of 22 FGF members produced by fibroblast cells. Cell signaling during physiological processes of angiogenesis and wound healing occurs when hFGF1 binds to its receptor (FGFR). However, when heterogenous homeostasis is not maintained, fibroblast cells exhibit excessive proliferation which can lead to a myriad of cancers. smFRET is an ultrasensitive distant dependent (1-10 nm) technique capable of resolving such heterogeneity in structural dynamics and binding affinities (Kd). Therefore, we successfully designed and characterized fluorescently labeled hFGF1 tracers which span the visible light region of the electromagnetic spectrum for use in …

Advancing The Preclinical Development Of Secondary Metabolites From Cacospongia Mycofijiensis For The Treatment Of Cancer, Joseph Morris

Natural Sciences and Mathematics | Biological Sciences Master's Theses

The marine sponge Cacospongia mycofijiensis from the Indo-Pacific has proven to be a source of structurally diverse secondary metabolites that are biologically active against a variety of distinct targets. Current interest in the secondary metabolites of C. mycofijiensis largely stems from a) their potent and preferential cytotoxicity for cancer cell lines versus normal cells, making many of them promising leads as cancer therapeutics and b) the novel mechanisms of action responsible for their impressive cytotoxicity. However, limited compound availability has resulted in a paucity of studies aimed at advancing the preclinical development of these secondary metabolites from C. mycofijiensis for …

Biomedical Applications And Syntheses Of Selected Anthraquinone Dyes, Richard Sirard

Senior Honors Theses

Anthraquinones are aromatic organic compounds that have multiple applications in the biomedical field. Some anthraquinone-based compounds are used as fluorophores to contrast cell nuclei while others act as chemotherapeutic agents. However, there are not many fluorescent anthraquinone cell stains currently available. In this study, commercially available anthraquinone dyes, in addition to other dye families and compounds, were reviewed for their unique properties, advantages, and drawbacks. The development and characterization of three novel anthraquinone fluorophores revealed promising photophysical characteristics, like large Stokes shifts. One of the compounds, RBS3, was chosen for fixed and live cell staining and exhibited desirable biomedical properties. …

Pegylated Block Copolymer For Cancer Imaging And Treatment, Sweety Singh

Dissertations

Gene theranostics have emerged as an important tool for the treatment of cancer as well as other diseases. Among the challenges in this field is the lack of effective vectors to chaperone plasmids into cells while the vector itself exhibits minimal toxicity. Herein, the synthesis, cellular uptake, and gene delivery using a biocompatible norbornene-based block copolymer is reported. This block copolymer, bearing polyethylene glycol moieties along with primary amines is functionalized with both a boron dipyrromethene (BODIPY) fluorophore for fluorescence tracking and a folic acid derivative for cancer cell targeting.

Stoichiometry control afforded residual unreacted amine functional groups available to …

Toxicity Analysis Of 2’-Deoxyguanosine-N2-6-Aminopyrene And 2’-Deoxyguanosine-N2-8-Aminopyrene In Escherichia Coli, Emily Janeiro

Honors Scholar Theses

Cancer is a disease that stems from genomic errors that are not corrected properly by cellular repair mechanisms. Errors are more likely to form when organisms are subjected to DNA damage by mutagenic compounds. 1-Nitropyrene, a nitrated polycyclic aromatic hydrocarbon (nitro-PAH), has been shown to be a potent mutagen that causes cancer. Nitro-PAHs can arise from diesel exhaust products in the environment. Out of all nitro-PAHs, 1-nitropyrene is found in largest quantities in the environment. This poses a great need to study its effects biochemically in order to address its toxicity in DNA. Other nitropyrene derivatives, including 1,6-dinitropyrene and 1,8-dinitropyrene, …

Design, Synthesis, And Characterization Of Chemical Tools To Study Peroxisomal Import, Jhalak N. Timilsena

Masters Theses

Peroxisomes are dynamic and interconnected single lipid membrane bound organelles found in the eukaryotic cells which are involved in various biochemical processes including the b-oxidation of very long chain and branched chain fatty acids, metabolism of reactive oxygen and nitrogen species, and reduction of hydrogen peroxide among others. These organelles are known to host numerous proteins and enzymes depending on the cellular environment. All of the proteins needed in the peroxisomes are encoded in the nucleus and synthesized in the cytosol which are then transported to the peroxisomes with the help of a sophisticated protein-transport machinery. Pex5 is one of …

Conformationally-Controlled Late-Stage Modifications For Sar Studies Of The C-3-Glcp Moiety Of Ipomoeassin F, Lucas Whisenhunt

Graduate Theses and Dissertations

The resin glycoside, ipomoeassin F has been shown to be extremely potent against multiple cancer lines (IC50 = 4.2-36 nM). However, the mechanism of action of this potent and complex natural product is still not fully understood. The α,β-unsaturated esters of the glucosyl moiety have been shown to be vital for the overall cytotoxicity of ipomoeassin F. Nevertheless, the importance of the tigloyl ester of the glucosyl moiety is still largely unknown. This work aimed to study the pharmacophore importance of the tigloyl ester by creating, an efficient, scalable, and flexible synthesis route for various analogs. The 18-linear step synthesis …

Do Paraben Derivatives Alter T Cell Immunity?, Hailey Kintz

Spring Presentation of Undergraduate Research

T cells immunity is linked to a complex system of cytokines that determine differentiation of naïve T cells into Th1, Th2, Th17, and Treg cells. Estrogen production or periods of elevated production have been correlated with an anti-inflammatory state in which Th2 and Treg cells are up-regulated. Such responses in the immune system are capable of supporting pre-cancerous activity. We are investigating the tie between the xenoestrogen compounds found in cosmetics, parabens, and their ability to regulate T cell immunity. Testing parabens and paraben derivatives with weaker estrogen receptor association will allow for a better understanding of the interplay between …

Review Of Ligand Specificity Factors For Cyp1a Subfamily Enzymes From Molecular Modeling Studies Reported To-Date, Jayalakshmi Sridhar, Navneet Goyal, Jiawang Liu, Maryam Foroozesh

Faculty and Staff Publications

The cytochrome P450 (CYP) family 1A enzymes, CYP1A1 and CYP1A2, are two of the most important enzymes implicated in the metabolism of endogenous and exogenous compounds through oxidation. These enzymes are also known to metabolize environmental procarcinogens into carcinogenic species, leading to the advent of several types of cancer. The development of selective inhibitors for these P450 enzymes, mitigating procarcinogenic oxidative effects, has been the focus of many studies in recent years. CYP1A1 is mainly found in extrahepatic tissues while CYP1A2 is the major CYP enzyme in human liver. Many molecules have been found to be metabolized by both of …

Micro-Spectroscopy Of Bio-Assemblies At The Single Cell Level, Jeslin Kera

Honors Undergraduate Theses

In this thesis, we investigate biological molecules on a micron scale in the ultraviolet spectral region through the non-destructive confocal absorption microscopy. The setup involves a combination of confocal microscope with a UV light excitation beam to measure the optical absorption spectra with spatial resolution of 1.4 μm in the lateral and 3.6 μm in the axial direction. Confocal absorption microscopy has the benefits of requiring no labels and only low light intensity for excitation while providing a strong signal from the contrast generated by the attenuation of propagating light due to absorption. This enables spatially resolved measurements of single …

Oleanolic Acid Inhibits High Salt-Induced Exaggeration Of Warburg-Like Metabolism In Breast Cancer Cells, Suneetha Amara, Mu Zheng, Venkataswarup Tiriveedhi

Chemistry Faculty Research

Cancer cells have a proliferative advantage by utilizing intermediates of aerobic glycolysis (Warburg effect) for their macromolecule synthesis. Although the exact causes of this Warburg effect are unclear, high osmotic stress in solid tumor microenvironment is considered one of the important factors. Oleanolic acid (OA) is known to exert anti-inflammatory and anti-cancer effect. In our current studies, using breast cancer cell lines, we determined the protective role of OA in high salt-mediated osmotic stress-induced cancer growth. Hypertonic (0.16 M NaCl) culture conditions enhanced the cancer cell growth (26 %, p < 0.05) and aerobic glycolysis as marked by increased glucose consumption (34 %, p < 0.05) and lactate production (25 %, p < 0.05) over untreated cells. This effect was associated with increased expression and activity of key rate-limiting enzymes of aerobic glycolysis, namely hexokinase, pyruvate kinase type M2, and lactate dehydrogenase A. Interestingly, this high salt-mediated enhanced expression of aerobic glycolytic enzymes was efficiently reversed by OA along with the decreased cancer cell proliferation. In cancer cells, enhanced aerobic glycolysis is associated with the decreased mitochondrial activity and mitochondrial-associated caspase activity. As expected, high salt further inhibited the mitochondrial related cytochrome oxidase and caspase-3 activity. However, OA efficiently reversed the high salt-mediated inhibition of cytochrome oxidase, caspase activity, and pro-apoptotic Bax expression, thus suggesting that OA induced mitochondrial activity and enhanced apoptosis. Taken together, our data indicate that OA efficiently reverses the enhanced Warburg-like metabolism induced by high salt-mediated osmotic stress along with potential application of OA in anti-cancer therapy.

Anticancer, Biophysical And Computational Investigations Of Half-Sandwich Ruthenium(Ii) Thiosemicarbazone Complexes: The Effect Of Arene Versus Thiacrown Face-Cap, Floyd A. Beckford, Alyssa Stott, P. Canisius Mbarushimana, Marc-Andre Leblanc, Kinsey Hall, Samantha Smith, Jimmie L. Bullock, Dennis J. Houghton, Alvin A. Holder, Nikolay Gerasimchuk, Antonio Gonzalez-Sarrías

Chemistry & Biochemistry Faculty Publications

A series of half-sandwich ruthenium complexes, two containing an arene face-cap and the other a thiacrown ether face-cap were synthesized to investigate the necessity of the arene for anticancer activity in this class of compounds. The complexes are formulated as [(h⁶-p-cymene)Ru(dmabTSC)Cl]PF₆, [(h⁶-benzene)Ru(dmabTSC)Cl]PF₆ (arene complexes), and [([9]aneS₃(dmabTSC)Cl]PF₆ (dmabTSC = dimethylaminobenzaldehye thiosemicarbazone). It was observed that none of the complexes showed good anticancer activity in vitro against HCT-116 and Caco-2 (colon adenocarcinoma) cells. All three complexes can bind strongly to calf-thymus DNA with binding constants on the order of 10 …

Effect Of Quercetin, Genistein And Kaempferol On Glutathione And Glutathione-Redox Cycle Enzymes In 3t3-L1 Preadipocytes, William Y. Boadi, Paul K. Amartey, Andrew Lo

Chemistry Faculty Research

Context and objective: Many studies have shown that cellular redox potential is largely determined by glutathione (GSH), which accounts for more than 90% of cellular nonprotein thiols. The aim of this study was to delineate the effect of three flavonoids – namely, quercetin, kaempferol and genistein – and exogenous GSH on oxidative damage by the Fenton’s pathway through the GSH and GSH-redox cycle enzymes in 3T3-L1 cells. Materials and methods: 3T3-L1 preadipocytes were exposed to each flavonoid and GSH at concentrations of 0, 5, 10, 15, 20 and 25 µM and then GSH levels and activities of glutathione peroxidase (GSH-Px), …

Violacein Induces P44/42 Mitogen-Activated Protein Kinase‑Mediated Solid Tumor Cell Death And Inhibits Tumor Cell Migration, Toral Mehta, Koen P. Vercruysse, Terrance Johnson, Anthony Okechukwu Ejiofor, Elbert Myles, Quincy A. Quick

Chemistry Faculty Research

Microbial secondary metabolites have emerged as alternative novel drugs for the treatment of human cancers. Violacein, a purple pigment produced by Chromobacterium violaceum, was investigated in the present study for its anti‑tumor properties in tumor cell lines. Clinically applicable concentrations of violacein were demonstrated to inhibit the proliferative capacity of tumor cell lines according to a crystal violet proliferation assay. The underlying mechanism was the promotion of apoptotic cell death, as indicated by poly(ADP ribose) polymerase cleavage and p44/42 mitogen‑activated protein kinase signaling determined by western blot analysis. Collectively, this provided mechanistic evidence that violacein elicits extracellular-signal regulated kinase‑induced apoptosis …

Inhalable Nanocomposites And Anticancer Agents For Cancer Therapy, Nathanael A. Stocke

Theses and Dissertations--Chemical and Materials Engineering

Cancer is designated as the leading cause of mortality worldwide and lung cancer is responsible for nearly 30% of all cancer related deaths. Over the last few decades mortality rates have only marginally increased and rates of recurrence remain high. These factors, among others, suggest the need for more innovative treatment modalities in lung cancer therapy. Targeted pulmonary delivery is well established for treating pulmonary diseases such as asthma and provides a promising platform for lung cancer therapy. Increasing local deposition of anticancer agents (ACAs) and reducing systemic exposure of these toxic moieties could lead to better therapeutic outcomes and …

Small Molecule Tyrosine Kinase Inhibitors Of Erbb2/Her2/Neu In The Treatment Of Aggressive Breast Cancer., Richard L. Schroeder, Cheryl L. Stevens, Jayalakshmi Sridhar

Faculty and Staff Publications

he human epidermal growth factor receptor 2 (HER2) is a member of the erbB class of tyrosine kinase receptors. These proteins are normally expressed at the surface of healthy cells and play critical roles in the signal transduction cascade in a myriad of biochemical pathways responsible for cell growth and differentiation. However, it is widely known that amplification and subsequent overexpression of the HER2 encoding oncogene results in unregulated cell proliferation in an aggressive form of breast cancer known as HER2-positive breast cancer. Existing therapies such as trastuzumab (Herceptin^®) and lapatinib (Tyverb/Tykerb^®), a monoclonal antibody inhibitor …