Nanoparticles (NPs) use for drug delivery or vaccines is highly successful. Given this, optimizing a NP's biological identity for maximal therapeutic benefit remains challenging. Macromolecules absorption from biofluids by NPs forms a layer called the protein corona. Herein, we examined a corona's influence on the uptake of polymeric NPs, made with a hyperbranched polyester polymer (HBPE), by breast cancer cells. Moreover, a corona's ability to increase cancer killing through improved paclitaxel (taxol) drug delivery was evaluated. Normal and influenza A virus (IAV)-infected mice sera were employed as coronal protein sources. Pre-coating NPs with sera may enrich NP surfaces with proteins that favor cancer interaction. In turn, a NP's ability to reach tumors may be enhanced by exploiting normal or IAV sera content. For normal and IAV sera studies, polyethylene glycol (PEG), a gold-standard NP surface modification for in vivo delivery, served as a control to sera-incubated HBPE-NPs. Sera pre-coated HBPE-NPs exhibited enhanced breast cancer cell uptake and tumor localization, over PEGylated HBPE-NPs. Additionally, breast cancer treatment with sera pre-coated HBPE-NPs resulted in greater taxol-mediated killing compared to PEGylated HBPE-NP treatment. Sera pre-coated HBPE-NPs additionally demonstrated greater uptake in cancer cells in an in vitro transwell system. The transwell system involved NP treatment in an upper chamber containing endothelial cells and assaying NP uptake in a lower chamber containing cancer cells. IAV sera coating enhanced NP localization to breast cancer tumors, while lowering liver and spleen accumulation in mice. We show HBPE-NPs incubation with normal and immune response-derived IAV sera can form coronas with unique proteins. Our findings suggest that sera collected during an immune response to infection are a rich source of coronal proteins that could form the basis of a preformed protein corona that ensures the optimal biological identify for targeted cancer cell uptake as described herein.

This research aims to evaluate two new pharmaceuticals on the market. Rimegepant and Lasmiditan target the trigeminovascular system and respectively, are characterized in the gepant and ditan classes of pharmaceuticals. Based on a review of studies, Rimegepant was determined to be the advantageous acute treatment. This is not conclusive due to inequivalent comparison in sample size and amount of research completed. It is encouraged for additional research to be imposed before a conclusive determination of the advantageous acute treatment can be distinguished.

Διάχυτη είναι η γνώμη ότι έχουμε εισέλθει σε μια νέα εποχή, η οποία προσδιορίζεται ως εποχή της παγκοσμιοποίησης. Όπως δείχνουν οι διάφορες μελέτες και αναλύσεις, την παγκοσμιοποίηση την ωθούν και προσπαθούν να την επιβάλλουν οι πολυεθνικές και οι υπερεθνικές εταιρίες και οι θυγατρικές τους σε διάφορες χώρες, που στοχεύουν στη διάθεση των προϊόντων τους, στην διατήρηση του ανταγωνιστικού πλεονεκτήματός τους αλλά και στη μεγιστοποίηση των κερδών τους. Στα πλαίσια της δηµιουργίας της Ευρωπαϊκής Κοινότητας, (ΕΚ) δηµιουργήθηκε και η ανάγκη ύπαρξης µιας κοινής εσωτερικής αγοράς, που θα είχε ελευθερία κινήσεων, δηλαδή ελευθερία στην κυκλοφορία των εργαζομένων, των αγαθών, των υπηρεσιών και των κεφαλαίων. Οι συνθήκες που έχουν διαμορφωθεί διεθνώς και δεδομένου της παγκόσμιας πλέον νέας οικονομίας τις τελευταίες δεκαετίες, είχαν σαν αποτέλεσμα την έντονη επιθυμία των επιχειρήσεων να επεκταθούν και να κατακτήσουν μια από τις κορυφαίες θέσεις σε παγκόσμιο επίπεδο με τη βοήθεια στρατηγικών ανάπτυξης. Μέσα σ’ αυτό το περιβάλλον της παγκοσμιοποίησης λειτουργεί και η φαρμακευτική βιομηχανία, που αποτελεί το αντικείμενο της εργασίας μας. Σκοπός μας είναι η αποτύπωση των πλεονεκτημάτων και μειονεκτημάτων του τρόπου λειτουργίας της για την ασφάλεια των πολιτών, καθώς ο τομέας της υγείας είναι πολύ σοβαρός. Θα αναφερθούμε στις προκλήσεις από τις παγκόσμιες εξελίξεις στον τομέα της υγείας, που είναι οι κάτωθι: - Η ορθολογική χρήση και η ασφάλεια της υγείας των ασθενών - Η προσπελασιμότητα, η διαθεσιμότητα και η ποιότητα των φαρμάκων - Η καινοτομία, η πληροφόρηση και η διαφάνεια και πως αυτές υιοθετούνται από τις φαρμακευτικές εταιρείες κατά τις διεθνείς συνεργασίες που συνάπτονται, αλλά και στο παγκόσμιο εμπόριο φαρμάκων. Οι παράγοντες καθορισμού στρατηγικών ανάπτυξης, ο κώδικας δεοντολογίας, η κατοχύρωση πνευματικών δικαιωμάτων (πατέντα), οι επενδύσεις στην έρευνα και ανάπτυξη φαρμάκων, αποτελούν τους σημαντικότερους παράγοντες για την ανάπτυξη της φαρμακοβιομηχανίας. Μέσω αυτών η φαρμακευτική βιομηχανία θα διαδραματίσει σημαντικό ρόλο στον παγκόσμιο χάρτη υγείας των λαών και στις μελλοντικές οικονομικές εξελίξεις για την ανάπτυξη τόσο της ίδιας όσο και των κρατών που δραστηριοποιείται. / Diffuse is the opinion that we have entered in a new season, which is defined as the season of globalization. As shown by various studies and analysis, push globalization and try to impose her the multinational and transnational companies and their subsidiaries in different countries that aim exclusively in the maximization of their profits. As part of creating the European Community (EC, created the need for a common internal market, which would have freedom of movement, namely freedom of movement for workers, goods, services and capital. The conditions that have emerged internationally and in most of the new global economy in recent decades, resulted in the strong desire of the enterprises to expand and conquer one of the top positions at global level through development strategies. In this environment of globalization is functioning also the pharmaceutical industry, that is the subject of our work. Our aim is to reflect the advantages and disadvantages of her operation for the citizens safety, as the sector of health is serious. We will refer the challenges of global developments in health, which are the following: - The rational use and security of patient health - The accessibility, availability and quality of medicines - Innovation, information and transparency and how they are adopted by pharmaceutical companies, not only in international cooperation agreements, but also to the global medicines trade. The determining factors of development strategies, the code of ethics, the ensure of intellectual property (patent), the investments in the research and drugs development, are the major factors for the development of pharmaceutical industry. Through them, the pharmaceutical industry will play an important role on the world map in the future economic trends, not only for her own development but also the development of the states that is been activated.

Ziel dieser Arbeit war die Herstellung fluoreszent markierter Präpolymere sowie deren Optimierung, die kontrollierte und reproduzierbare Synthese von redox-sensitiven und nicht redox-sensitiven NG mit und ohne Fluoreszenzmarkierung in einem durchschnittlichen Partikelgrößenbereich von 150 – 300 nm und mit einer Konzentration > 10*10 Partikel/ml, die Charakterisierung der NG, ihre Untersuchung bezüglich ihrer Stabilität und des Assoziationsverhaltens zu BSA sowie die Erlangung von Erkenntnissen bezüglich des Aufnahmemechanismus der NG in Abhängigkeit vom Transportpeptid Tat. Abschließend kann zusammenfassend gesagt werden: 1. Das große Potential von PG-basierten NG für biologische bzw. medizinische Einsatzgebiete konnte weiter untermauert werden. 2. Das mit Cy5-Alkin markierte PG PG-SH-Cy5 erscheint aufgrund des relativ hohen erreichten Markierungsgrades bei der Herstellung als aussichtsreichster Kandidat für weitere Untersuchungen. Diese Umsetzung besitzt noch Optimierungspotentiale bezüglich einer Verringerung des Polymerverlusts bei der Aufarbeitung, des erreichbaren Markierungsgrades und der Markierungsausbeute. Möglichkeiten, dies zu erreichen, wurden diskutiert. 3. Klare Aussagen über den Einfluss des esterhaltigen bzw. esterfreien Ausgangspolymers PG-SH auf die Konzentration und die Partikelgröße konnten aufgrund einer nicht ausreichenden Datenlage nicht getroffen werden. 4. Die esterhaltigen PG-SH-Moleküle erscheinen aufgrund ihrer Labilität gegenüber Hydrolyse für die NP-Synthese weniger geeignet (geringere Stabilität). 5. Die Charakterisierung der aus den markierten und unmarkierten Ausgangspolymeren hergestellten NG, welche teilweise zusätzlich mit dem Transportpeptid Tat funktionalisiert wurden, erfolgte mittels NTA und zeigt für die meisten Spezies relativ schmale, gut definierte, monomodale Größenverteilungen mit einem Maximum um 100-200 nm im Bereich von ca. 40 – max. 400 nm mit Partikelkonzentrationen im Bereich von 1010 - 1011 Partikeln/ml. 6. Insgesamt konnte gezeigt werden, dass der untersuchte, von PG-SH abgeleitete NP-Typ (z. B. NG_3, redox-sensitiv unmarkiert) aufgrund seiner Einheitlichkeit, Partikelgröße und der Reproduzierbarkeit der Herstellung als gut geeignet für den geplanten Einsatz in biologischen Systemen erscheint. Von den weiter derivatisierten NG erscheinen die folgenden aufgrund der oben geschilderten Kriterien als besonders geeignet für den geplanten Einsatz in biologischen Systemen und weiterer Untersuchungen wert: NG680_(TAT)_1-4 (redox-sensitiv, markiert), NGCy5_(TAT)_1 (redox-sensitiv, markiert), NG_MA_2 (nicht redox-sensitiv, unmarkiert), NGCy7_MA_1 (nicht redox-sensitiv, markiert). Aufgrund des relativ hohen erreichbaren Markierungsgrades bei der Markierung der Ausgangspolymere erscheinen die mit Cy5-markierten Verbindungen als besonders vorteilhaft. 7. Die esterfreien, redox-sensitiven NP erwiesen sich bei 14-tägiger Lagerung unter physiologischen Bedingungen als stabil. Ihre Konzentration nahm über 14 Tage um ca. 60 % vom Ausgangswert ab. Gleichzeitig nahm der Teilchendurchmesser während des Beobachtungszeitraums um ca. 25 % zu. Die Abnahme der Teilchenzahl ist - zumindest teilweise - durch eine Vergrößerung des mittleren Teilchendurchmessers und mögliche Adsorptionseffekte an die Gefäßwände des Versuchsaufbaus zu erklären. 8. Die Konzentration der esterfreien, nicht redox-sensitiven NP verringert sich bei 14-tägiger Inkubation unter physiologischen Bedingungen deutlich auf ca. 10 % des Ausgangswerts. Der mittlere Durchmesser der Partikel bleibt innerhalb des Untersuchungszeitraums innerhalb der Fehlergrenzen konstant. Die starke Abnahme der Partikelkonzentration ist wahrscheinlich auf die Hydrolyse des verwendeten esterhaltigen Crosslinkers PEGDA zurückzuführen. Desweiteren sind Adsorptionsphänomene an Oberflächen des Versuchsaufbaus nicht auszuschließen. Insgesamt hervorzuheben ist die wesentlich höhere Stabiliät der redox-sensitiven NP unter den Versuchsbedingungen. Diese Substanzklasse sollte daher weiter verfolgt werden. 9. Es wurde gezeigt, dass sowohl die NG, die das Aufnahmeprotein Tat enthalten, als auch die NG ohne Tat mit Fluoreszenz-markiertem BSA (8,3 µg/ml) wechselwirken und zusammen mit diesem bei der Zentrifugation abgeschieden werden. Über die Art der Wechselwirkung kann keine Aussage getroffen werden. 10. Durch in vitro Zellaufnahmeuntersuchungen an Hela-Zellen konnte gezeigt werden, dass die mit Tat funktionalisierten, redox-sensitiven, Fluoreszenz-markierten NP von den Zellen aufgenommen werden. Die Aufnahme erfolgt über eine deutlich erkennbare Vesikelbildung, die an der Plasmamembran verstärkt beobachtet werden kann. Im Gegensatz hierzu konnte bei den nicht mit Tat funktionalisierten NP keine vergleichbare in vitro Zellaufnahme beobachtet werden. Die Ergebnisse dieser Arbeit bestätigen insgesamt das große Potential der von Thiol-funktionalisierten PG abgeleiteten NG für die medizinische Forschung und zukünftige Anwendungen in der Diagnostik und Therapie. Es wird eine Reihe von Ansatzpunkten aufgezeigt, auf deren Basis weitere vertiefende Untersuchungen zur Charakterisierung und Optimierung sowie zu zukünftigen nutzbringenden Anwendungen vorgenommen werden sollten. / Summary: Fluorescent Poly(glycidol)-based Nanogels - Synthesis, characterization and their interactions in vitro

Apixaban is a novel oral anticoagulant that prevents clotting by directly inhibiting Factor Xa in the coagulation cascade. Due to its different pharmacokinetics, previous standards for testing anticoagulant concentrations are ineffective at measuring apixaban. In this study, Hyphen Biomed Biophen Direct Xa Inhibitor and Biophen Heparin chromogenic kits from Aniara Diagnostica were used along with a NanoDrop™ One/OneC Microvolume UV-Vis Spectrophotometer to see if either of these kits provide acceptable precision and accuracy for the quantification of apixaban in plasma samples, as well as if there is a significant difference in these two kits at varying concentrations of apixaban. Apixaban is a novel oral anticoagulant that prevents clotting by directly inhibiting Factor Xa in the coagulation cascade. Due to its different pharmacokinetics, previous standards for testing anticoagulant concentrations are ineffective at measuring apixaban. In this study, Hyphen Biomed Biophen Direct Xa Inhibitor and Biophen Heparin chromogenic kits from Aniara Diagnostica were used along withused witha NanoDrop™ One/OneC Microvolume UV-Vis Spectrophotometer to see if either of these kits provide acceptable precision and accuracy for the quantification of apixaban in plasma samples,as well as and to evaluate if there is a significant difference in these two kits at varying concentrations of apixaban.

The adenosine system has become a promising target for the treatment of schizophrenia due to its unique relationship with dopamine D2 receptors. Dopamine D2 receptors display heightened sensitivity in schizophrenia, and inhibition of these receptors has been shown to alleviate some of the psychotic symptoms of the disorder. Inhibition of adenosine A(2A) receptors has been shown to decrease dopamine D2 receptor sensitivity, making this receptor a potential target for treatment of the disorder. This effect occurs because adenosine A(2A) receptors form a mutually inhibitory heterodimeric complex with dopamine D2 receptors. The present study looked at the effects of an adenosine agonist on prepulse inhibition (PPI) and cyclic-AMP response binding element protein (CREB) concentrations in the nucleus accumbens (NAc) using a rodent model of schizophrenia (NQ model) that presents with increased D2 receptor sensitivity. Results showed that the A(2A) agonist was effective in improving PPI in NQ-treated animals. The agonist was also effective in reducing increased CREB concentrations in the NAc of NQ-treated animals to control levels. The effectiveness of the agonist suggests that the adenosine system may be a viable target for the treatment of some of the psychotic symptoms associated with schizophrenia.

Pulmonary fibrosis (PF) is a serious lung disease, as its life expectancy is only 3-5 years upon occurrence and more than 50 % of the cases are idiopathic, i.e., unknown cause. Two drugs, pirfenidone (PIR) and nintedanib, have recently been approved; however, their efficacies are moderate without evidence of prolonged survival. While this is primarily due to our insufficient knowledge about key PF pathogenesis, inductions of oxidative stress and transforming growth factor-b1 (TGF-b1) have been suggested in PF lungs. Hence, anti-oxidative melatonin (MEL) and curcumin (CUR) have been studied yet their efficacies remain moderate without clear understanding about the mechanisms of action. Accordingly, this project hypothesized that a novel hybrid molecule of MEL and CUR, AM24, was a more potent inhibitor against oxidative stress and TGF-b1 induced PF pathobiologic events than MEL or CUR, so that its pulmonary delivery enabled therapeutic intervention in an animal model of PF. Free radical scavenging activity and various in vitro lung cell-based anti-fibrotic activities of AM24 were determined and compared with those of MEL and CUR as well as their admixture (MEL+CUR) and PIR. Pulmonary administration of AM24 was then examined for therapeutic intervention in a rat model of bleomycin (BLM)-induced experimental PF. AM24 was equipotent to MEL, but less potent than CUR in the hydrogen peroxide-induced free radical (ABTS) scavenging assay, ranked with the half-maximal inhibitory concentration (IC50) of 25.7, 32.0 and 11.4 uM, respectively. However, in the in vitro human lung fibroblast systems, AM24 was shown to be more potent than MEL or CUR and notably than MEL+CUR or PIR in the TGF-b1 induced 1) collagen synthesis by the picrosirius red assay, 2) proliferation by the MTT assay; and 3) differentiation to myofibroblast by western blot analysis of a myofibroblast marker, a-smooth muscle actin (a-SMA). In detail, at 10 uM, AM24 inhibited TGF-b1 induced 1) collagen synthesis by 90 %; 2) proliferation by ~72 %; and 3) differentiation to myofibroblast completely, while MEL, CUR, MEL+CUR and PIR resulted in 30-55 % or insignificant inhibition. In addition, in the in vitro human lung alveolar epithelial cell system, AM24 at 10 uM almost completely inhibited TGF-b1 induced epithelial-mesenchymal transition (EMT), as measured with western blot expressions of an epithelial marker, E-cadherin, and a mesenchymal marker, vimentin. Again, MEL, CUR, MEL+CUR and PIR exerted much less inhibitory activities. Hence, all these results consistently suggested that AM24 was a unique hybrid molecule of MEL and CUR and possessed highly potent anti-fibrotic activities in addition to the free radical scavenging activity. AM24 was then examined for therapeutic intervention in an in vivo rat model of BLM-induced PF. BLM was orotracheally spray-dosed to the lungs at 0.6 mg/kg on day 1 to develop experimental PF in 14 days. Lung administrations of AM24 at 0.1 mg/kg commenced at 6 hours of BLM induction on day 1 and continued thrice weekly over two weeks. Functional treadmill exercise endurance was measured on day 12 and 15; and lungs were harvested upon sacrifice on day 16. Overall, AM24 showed significant intervention activities as follows: 1) exercise endurance was reduced only ~20%, much lower than 78% of the untreated PF rats; 2) reduced fibrotic tissue area and alveolar structural destruction were seen by histological examinations; and 3) lung’s induced collagen deposition was inhibited by ~78 %. However, unlike the literature, the lung’s TGF-b1, PCNA (a cell proliferation marker), and a-SMA (a differentiation marker), were not largely induced in the BLM-induced PF model, so that the intervention activities of AM24 to these markers were not clearly shown. In contrast, induced EMT was seen in the BLM-induced model, represented by increased mesenchymal marker, vimentin, and by decreased epithelial marker, E-cadherin; and AM24 appeared to counter this induced EMT. Accordingly, while the BLM-induced PF model may need further optimizations for clearer pathogenic changes, AM24 exerted certain degree of in vivo efficacies with a lung dose of 0.1 mg/kg, which was much lower than the effective doses of MEL, CUR, PIR and nintedanib seen in the literature with BLM induced PF model. In conclusion, this thesis study has provided an early proof-of-concept for AM24, a novel MEL-CUR hybrid molecule, being potently anti-oxidative and anti-fibrotic in the in vitro lung cell-based assessments. As a result, AM24 enabled therapeutic intervention just with a lung dose of 0.1 mg/kg in the BLM-induced rat model of experimental PF.

Mergers and acquisitions (M&As) are one of the most important strategies for pharmaceutical and the biotechnology industry to gain access to valuable technological resources in recent years. The M&As activities and outcomes of famous pharmaceutical company ¡V Roche, and biotech leading company ¡V Genentech were investigated in this study. Thus, the innovation, product pipeline and financial performance were examined to elucidate the crucial strategies of M&As. Nowadays, the challenges of pharmaceutical company includes the growth rate of research and development (R&D) cost were higher than sales¡¦, new drugs development were slower than industry demand, licensing from other company and high profit patent drugs turned into generics. By innovative and vigorous development of biotechnology, biotech companies were devoted into niche products includes nucleic acid or protein drugs. However, large R&D expenditure and high risk product development result in capital shortage problems. The abundant working capital and well-experienced manufacture, marketing and sales characteristics of big pharma enable the M&As of pharma and biotech arise. This study case describe the M&A of an over a century pharmaceutical company ¡V Roche with a first IPO biotech company ¡V Genentech. To survey the process of licensing, merger, acquisition and public offerings, the motivation, strategies and outcomes were examined. In 2006, over the half of top ten sales of Roche were derived from Genentech; therefore, the global marketing and brand value of Roche contribute Genentech into the top one market value biotech company. The synergistic effect seems the M&A is a perfect integration. However, the majority equity owned by Roche and the oversea sales licensing to Roche were the further underlying problems for Genentech to expand to the top health care company in the world. The development of pharmaceutical company becoming more concentrated that the top ten pharmaceutics account for half of the global sales. Moreover, with the growing demand from the health care, aging and novel therapeutics and under the threatens of health insurance payment and patent drug expired, the tide of M&As for pharmaceutical and biotech companies will not decline. The weakness of Taiwan pharmaceutics is poor in innovation and generic drugs-oriented manufacture; furthermore, the biotech industry is still beyond maturity. Under the waves of M&As, the Taiwan pharmaceutical and biotech industry may prompt development by M&As. In this case study, the pharmaceutics and biotech background were first introduced and the case history, M&A process and strategies, product portfolio, R&D and financial issues were explored. Therefore, this study may fulfill and provide some suggestions and references for further pharmaceutical and biotech M&A activities in Taiwan.

Metal catalysis of symmetric and asymmetric carbene transfer reactions has been widely applied in natural product synthesis and material science over years. Metal carbene can be easily generated from the extrusion of nitrogen under the catalysis of metal complexes to further undergo various organic reactions, O/N/C-H insertions, cycloadditions, and ylide formations. Currently, the dominant effective catalysts for carbene reactions are built with expensive precious metal, for example, rhodium, ruthenium, palladium, gold. Notably, the effective reactivity and enantioselectivity of the dirhodium(II) catalysts are researched and established over the decades. However, the use of precious metal catalysts is the major source of metal residues in pharmaceutical products; thus, it becomes a concerning safety factor towards the environment. Iron, instead, to our interest, is an economical and ecofriendly element. Iron has been used in different catalytic reactions but achieved moderate reactivity and low enantioselectivity towards carbene transfer reactions. Within, the electronic environment and the mechanism of iron catalysts are underdeveloped. A new series of ligands named bis(imino)pyridine family has been found to be able to offer coordinate sites for transition metals to build effective metal complexes can be used for different organic reactions. This type of ligand can be easily synthesized in relatively short steps and the structure of the substituents can be facially tuned. These advantages show the great potential of bis(imino)pyridine ligands in organic catalysis. In this project, bis(imino)pyridine ligands were applied as the backbone structure to construct a series of achiral and chiral iron catalysts that were investigated in catalytic metal carbene reactions in terms of reactivity and selectivity. By manipulating the structure of the ligands, the high reactivity of the achiral iron(II) complexes towards various carbene reactions was achieved, while moderate enantioselectivity was observed by the catalysis of chiral iron(II) complexes. To our delight, the bis(imino)pyridine iron(II) complex, for the first time, is shown as an effective metal carbene catalyst for carbene transfer reactions of donor–acceptor diazo compounds. Its broad catalytic capability is demonstrated by a range of metal carbene reactions, from cyclopropanation, cyclopropenation, epoxidation, and Doyle–Kirmse reaction to O–H insertion, N–H insertion, and C–H insertion reactions. The asymmetric cyclopropanation of styrene and methyl phenyldiazoacetate was successfully achieved by the new chiral bis(imino)pyridine iron catalyst, which delivers a new gateway for the development of chiral iron catalysis for metal carbene reactions.

The small Molecule Drug Discovery field has been heavily dependent on suppressor discovery by structural binding prediction. Despite all successes in targeting different types of molecular targets in cells, many are considered undruggable. Over 85% of proteins and over 99% of RNAs are still considered hard to drug in cancer. The main challenge in suppressing their activity would be their unknown or super complicated structures. In addition, many of them present a dynamic 3D structure with no pocket. Since computational structural-based drug discovery has been developed for proteins with rigid structures and obvious pockets, it has not been successful in discovering small molecule candidate drugs against dynamic or unknown structures. In addition, structurally binding to some targets like RNAs does not guarantee their activity inhibition. Therefore, there has been a need for a computational approach to discover drugs against hard-to-drug targets with no structural information involved. I introduce a new small molecule drug discovery approach using Artificial Intelligence (AI), specifically Deep Learning (DL). This method does not require any input data from the sequence or the 3D structure of the target. Rather than targeting biomolecules' structure, AI models learn the biology of suppressing the target's activity called functional-based modeling. In three different projects, we prove the efficiency of AI-based functional-based drug discovery compared to traditional computational drug discovery. First, the collection of one of the biggest molecular datasets for molecular machine learning. MolData is one of the biggest categorized molecular datasets ever published for AI drug discovery. Second, I introduce RiboStrike, an AI-based model capable of discovering candidate drugs against micro RNAs. RiboStrike is the state-of-the-art model capable of discovering small molecule candidate drugs against RNA regardless of their size, structure, and coding functionality. We successfully discovered three candidate drugs against the functionality of miR21. Third, I introduce AMPdeep, an AI-based approach to discovering the hydrolysis of Anti-microbial Peptides (AMPs).