Global ETD Search

1	A comparison of safety and efficacy of cytotoxic versus molecularly targeted agents in pediatric phase I solid tumor oncology trials Dorris, Kathleen 19 April 2012 (has links) No description available. Surgery pediatric oncology solid tumor molecularly targeted drugs developmental therapeutics
2	Leishmanicidas potenciais: estudo da síntese de fármacos dirigidos dendriméricos de primeira geração com hidroximetilnitrofural / Potencial leishmanicides: synthesis study of first generation dendrimer targeted drugs with hydroxymethylnitrofurazone Soraya da Silva Santos 12 September 2012 (has links) A leishmaniose é considerada uma doença tropical extremamente negligenciada, que afeta regiões de extrema pobreza. Trata-se de doença emergente com alta morbidade e mortalidade. Aproximadamente 20 diferentes espécies de parasitas intracelulares obrigatórios do gênero Leishmania têm sido identificadas como patogênicas. Estes protozoários são transmitidos ao hospedeiro humano por meio da picada de insetos hematófagos, conhecidos como flebotomíneos. A quimioterapia é escassa, limitada e muito cara. Os fármacos disponíveis apresentam elevada toxicidade, bem como suscitam número elevado de casos de resistência. Considerando-se que a descoberta e o desenvolvimento de novos agentes leishmanicidas são extremamente necessários o objetivo deste trabalho foi contribuir com essa busca utilizando-se o método de modificação molecular, a latenciação. Tendo em vista que os dendrímeros têm sido muito utilizados como transportadores de fármacos, propôs-se a síntese de fármacos dirigidos dendriméricos de primeira geração de hidroximetilnitrofural (NFOH), composto que apresenta potencial atividade leishmanicida. Assim, pretendeu-se desenvolver fármacos dirigidos de NFOH, que apresentem ação seletiva nos macrófagos, devido à presença de manose na estrutura, além de fármacos dirigidos, que apresentem ação seletiva no parasita, devido à presença de inositol em sua estrutura. Variedade de métodos sintéticos foi utilizada com o intuito de obter os dendrímeros dirigidos propostos. Os estudos sintéticos desenvolvidos indicam a provável obtenção dos dendrímeros dirigidos de manose e de inositol, embora os produtos estejam impuros e sem o agente bioativo incorporado. A maior dificuldade encontrada foi a purificação dos compostos obtidos. Em adição, métodos de modelagem molecular foram empregados para compreender os mecanismos de liberação dos fármacos dendriméricos dirigidos de primeira geração. Características moleculares, tais como disponibilidade espacial e potencial eletrostático, foram avaliadas para predizer a região mais suscetível à ação enzimática com vistas à liberação do composto ativo. / Leishmaniasis is considered a superneglected tropical disease and affects primarily areas of extreme poverty. It represents an emergent illness with high morbidity and mortality. About 20 different species of intracellular parasites of Leishmania spp. have been identified as pathogenic. Those protozoans are transmitted to human hosts by means of the female phlebotomine sandflies bite. The chemotherapy is scarce, limited, and expensive. The drugs available can cause undesirable side effects and there are already reports of the increased number of drug resistance. Considering that, the discovery and the development of new leishmanicide agents are urgently needed, the objective of this work as to contribute to this search using the method of molecular modification, prodrug design. Taken into account that dendrimers can be used as drug carriers, the purpose of this work was the synthesis of first generation dendrimer targeted drugs of hydroxymethylnitrofurazone (NFOH), that shows potential leishmanicide activity. Thus, we designed NFOH targeted drugs with selective action in macrophages, due to the presence of mannose in the structure, and also NFOH targeted drugs that present selectivity for the parasite, due to the presence of inositol in the structure. Several synthetic methods have been used with the aim of synthesizing the targeted dendrimers with NFOH. Synthetic studies suggested the targeted dendrimers of D-mannose and of myo-inositol have been obtained, although impure and without the bioactive agent. The major difficulty was the purification of the compounds. In addition, molecular modeling methods were applied to understand the bioactive compound releasing from the first generation leishmanicide targeted dendrimers. Molecular features as spatial hindrance and electrostatic potential were evaluated to predict which region would be the most available to an enzymatic action regarding the bioactive compound release. Fármacos (Síntese) Fármacos dirigidos Leishmanicidas Quimioterápicos Chemoterapheutic Drugs synthesis Leishmanicides Targeted drugs
3	Leishmanicidas potenciais: estudo da síntese de fármacos dirigidos dendriméricos de primeira geração com hidroximetilnitrofural / Potencial leishmanicides: synthesis study of first generation dendrimer targeted drugs with hydroxymethylnitrofurazone Santos, Soraya da Silva 12 September 2012 (has links) A leishmaniose é considerada uma doença tropical extremamente negligenciada, que afeta regiões de extrema pobreza. Trata-se de doença emergente com alta morbidade e mortalidade. Aproximadamente 20 diferentes espécies de parasitas intracelulares obrigatórios do gênero Leishmania têm sido identificadas como patogênicas. Estes protozoários são transmitidos ao hospedeiro humano por meio da picada de insetos hematófagos, conhecidos como flebotomíneos. A quimioterapia é escassa, limitada e muito cara. Os fármacos disponíveis apresentam elevada toxicidade, bem como suscitam número elevado de casos de resistência. Considerando-se que a descoberta e o desenvolvimento de novos agentes leishmanicidas são extremamente necessários o objetivo deste trabalho foi contribuir com essa busca utilizando-se o método de modificação molecular, a latenciação. Tendo em vista que os dendrímeros têm sido muito utilizados como transportadores de fármacos, propôs-se a síntese de fármacos dirigidos dendriméricos de primeira geração de hidroximetilnitrofural (NFOH), composto que apresenta potencial atividade leishmanicida. Assim, pretendeu-se desenvolver fármacos dirigidos de NFOH, que apresentem ação seletiva nos macrófagos, devido à presença de manose na estrutura, além de fármacos dirigidos, que apresentem ação seletiva no parasita, devido à presença de inositol em sua estrutura. Variedade de métodos sintéticos foi utilizada com o intuito de obter os dendrímeros dirigidos propostos. Os estudos sintéticos desenvolvidos indicam a provável obtenção dos dendrímeros dirigidos de manose e de inositol, embora os produtos estejam impuros e sem o agente bioativo incorporado. A maior dificuldade encontrada foi a purificação dos compostos obtidos. Em adição, métodos de modelagem molecular foram empregados para compreender os mecanismos de liberação dos fármacos dendriméricos dirigidos de primeira geração. Características moleculares, tais como disponibilidade espacial e potencial eletrostático, foram avaliadas para predizer a região mais suscetível à ação enzimática com vistas à liberação do composto ativo. / Leishmaniasis is considered a superneglected tropical disease and affects primarily areas of extreme poverty. It represents an emergent illness with high morbidity and mortality. About 20 different species of intracellular parasites of Leishmania spp. have been identified as pathogenic. Those protozoans are transmitted to human hosts by means of the female phlebotomine sandflies bite. The chemotherapy is scarce, limited, and expensive. The drugs available can cause undesirable side effects and there are already reports of the increased number of drug resistance. Considering that, the discovery and the development of new leishmanicide agents are urgently needed, the objective of this work as to contribute to this search using the method of molecular modification, prodrug design. Taken into account that dendrimers can be used as drug carriers, the purpose of this work was the synthesis of first generation dendrimer targeted drugs of hydroxymethylnitrofurazone (NFOH), that shows potential leishmanicide activity. Thus, we designed NFOH targeted drugs with selective action in macrophages, due to the presence of mannose in the structure, and also NFOH targeted drugs that present selectivity for the parasite, due to the presence of inositol in the structure. Several synthetic methods have been used with the aim of synthesizing the targeted dendrimers with NFOH. Synthetic studies suggested the targeted dendrimers of D-mannose and of myo-inositol have been obtained, although impure and without the bioactive agent. The major difficulty was the purification of the compounds. In addition, molecular modeling methods were applied to understand the bioactive compound releasing from the first generation leishmanicide targeted dendrimers. Molecular features as spatial hindrance and electrostatic potential were evaluated to predict which region would be the most available to an enzymatic action regarding the bioactive compound release. Chemoterapheutic Drugs synthesis Fármacos (Síntese) Fármacos dirigidos Leishmanicidas Leishmanicides Quimioterápicos Targeted drugs
4	Flow-cytometrická analýza inhibičního vlivu nových cílených léčiv na aktivitu ABC lékových efluxních transportérů / Flow-cytometric analysis of inhibitory effect of novel targeted drugs on the activity of ABC drug efflux transporters Burianová, Gabriela January 2020 (has links) Charles University Faculty of Pharmacy in Hradec Kralove Department of Pharmacology & Toxicology Student: Gabriela Burianova Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Flow-cytometric analysis of inhibitory effect of novel targeted drugs on the activity of ABC drug efflux transporters Cancer is the second leading cause of death. Cancer treatment often combines conventional chemotherapy, radiation therapy and surgery. More recent approach to treatment is the use of targeted cancer therapy with a greater specificity towards cancer cells. Development of resistance is a major obstacle in the success of chemotherapy. Multidrug resistance (MDR) can be acquired through various mechanisms e.g. overexpression of efflux transporters. ATP binding cassette (ABC) transporters represents a large family of transmembrane proteins that use ATP to pump molecules across the membrane. The three main ABC proteins related to MDR are: P-glycoprotein (ABCB1), multidrug resistance-associated protein 1 (ABCC1) and breast cancer resistance protein (ABCG2). Use of ABC transporter inhibitors increases the amount of chemotherapeutical substrates accumulated within the cells. In this study we evaluated interactions of six synthetic small molecule inhibitors (alisertib, ensartinib, entrectinib, talazoparib,...
5	Combining doxorubicin and gemcitabine with targeted drugs as a treatment option for high-risk neuroblastoma Johannesson, Alexandra January 2023 (has links) Neuroblastom är en barncancer som uppstår ur det sympatiska nervsystemet och drabbar omkring 15 barn i Sverige varje år. Högriskvarianten är associerad med mycket hög dödlighet och risk för återfall, vilket tros ha att göra med att tumörernas ovanligt heterogena sammansättning tillåter resistenta subpopulationer att motstå konventionella behandlingsmetoder. Tidigare forskning har identifierat rubbade mekanismer för celldelning som ett tillvägagångssätt för tumörcellerna att överleva DNA-skador som kemoterapeutiska droger orsakar. I detta masterprojekt analyserades fem ultra-högrisk neuroblastomcellinjer i syfte att belysa deras progression genom celldelningen efter behandling med doxorubicin och/eller gemcitabin. Vidare identifierades ataxia telangesia mutated (ATM) serine/threonine kinase som ett essentiellt protein vid inhibering av celldelningen och i samband med reparation av DNA-skador, vilket bekräftades av förhöjt uttryck av fosforylerat ATM i alla fem cellinjer efter behandling med doxorubicin, gemcitabin, och/eller en kombination av båda. Återväxt av tumörcellerna efter inhibering av fosforylerat ATM i kombination med doxorubicin och gemcitabin analyserades sedan, och fördröjd återväxt noterades i en av cellinjerna efter kombinationsbehandling. Sammantaget har nya mekanismer för behandlingsresistens hos tumörceller identifierats och alternativa kombinationsbehandlingar har visat effekt på en av fem testade neuroblastomcellinjer. / Neuroblastoma is a pediatric cancer of the sympathetic nervous system that afflicts around 15 children annually in Sweden. Despite aggressive treatment, high-risk neuroblastoma is associated with a mortality of 50% and relapse rate of up to 60%, emphasizing the need for novel treatment options. In this study, fluoresce activated cell sorting was used to analyze cell cycle progression in five ultra-high-risk neuroblastoma cell lines: BE(2)-C, Kelly, SK-N-AS, SK-N-DZ, and SK-N-FI, post-treatment with doxorubicin and gemcitabine. In line with previous research, doxorubicin primarily induced cell cycle arrest in G2/M-phase and gemcitabine in the S-phase. Combined, the compounds induced varied effects, with accumulation primarily in the G1-and S-phase. Immunoblotting revealed elevated levels of phosphorylated ATM (pATM), a key regulator of cell cycle arrest and DNA damage signaling, across all five cell lines post-treatment to doxorubicin, gemcitabine, and/or the combination, indicating its vital role in their survival. Kelly stood out in both cell cycle progression and ATM phosphorylation, exhibiting minimal to no changes in cell cycle accumulation or pATM expression when exposed to the combined treatment, despite reacting to both monotherapies. These results may indicate that Kelly might implement an alternative mechanism of regulation compared to the remaining cell lines. To explore targeted inhibition of pATM, we employed the ATM kinase inhibitor KU-55933, which in BE(2)-C cells reduced expression levels of pATM when combined with doxorubicin, but not gemcitabine or the combination. Regrowth assays showed increased efficacy of doxorubicin and gemcitabine upon addition of the ATM kinase inhibitor KU-55933 in one of the tested cell lines in comparison to doxorubicin alone. However, longer incubation time is needed before the effect can be fully evaluated. These findings shed light on the differential cell cycle behavior in high-risk neuroblastoma cell lines exposed to combination therapy and suggest a vital role of ATM in the DNA damage response following doxorubicin and gemcitabine treatment. Further investigations are warranted to explore alternative strategies for enhancing the effectiveness of doxorubicin and gemcitabine in the treatment of this aggressive cancer subtype. neuroblastoma doxorubicin gemcitabine targeted drugs ATM neuroblastom doxorubicin gemcitabin målinriktade läkemedel ATM Biochemistry and Molecular Biology Biokemi och molekylärbiologi
6	Stanovení inhibičního vlivu vybraných cílených protinádorových léčiv na aktivitu ABC lékových efluxních transportérů / The assessment of inhibitory effects of selected targeted anticancer drugs on the activity of ABC drug efflux transporters Jurčáková, Júlia January 2021 (has links) Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Júlia Jurčáková Supervisor: RNDr. Jakub Hofman PhD. Title of diploma thesis: The assessment of inhibitory effects of selected targeted anticancer drugs on the activity of ABC drug eflux trasporters. Lung cancer is the leading cause of death within oncological diseases. Non-small cell lung carcinoma (NSCLC) accounts for about 85% of all lung cancer, and its major subtypes include adenocarcinoma and squamous cell carcinoma. In addition to surgery, radiotherapy and chemotherapy, the use of targeted low-molecular substances, which target tumor cells with higher specificity, has recently been used in treatment. The two main causes of death in cancer patients are the formation of metastases and the development of multidrug resistance (MDR). This may also be caused by overexpression of the efflux transporters. ATP-binding cassette (ABC) transporters are groups of transmembrane pumps that use energy in the form of ATP to transfer a wide range of substrates. In particular, P-glycoprotein (ABCB1), breast cancer-resistance protein (ABCG2) and multidrug resistance-associated protein 1 (ABCC1) are associated with MDR. Inhibition of these transporters increases the amount of cytostatic substrate within the...
7	Antimaláricos potenciais: planejamento e síntese de fármacos dirigidos de antimetabólitos de serina / Potential antimalarials: planning and synthesis of drugs directed serine antimetabolites Guilherme Costa Matsutani 02 December 2008 (has links) De acordo com a Organização Mundial da Saúde, AIDS,malária e tuberculose são as três maiores doenças infectantes do mundo, atingindo principalmente crianças. Regiões paupérrimas e de clima tropical, como a África sub-saariana, são as mais atingidas. Este quadro agrava-se com a disseminação de cepas do Plasmodium falciparum resistentes à cloroquina e multi-resistentes.Além disso, alguns fármacos utilizados na terapêutica da malária apresentam vários efeitos adversos, comprometendo o tratamento. Trata-se de um grande desafio e o seu enfrentamento requer estratégias. O desenvolvimento de novos quimioterápicos deve fundamentar-se em diferenças bioquímicas e morfológicas entre as células do hospedeiro e do parasita. A biossíntese de fosfolipídeos de membrana em parasitas do grupo Apicomplexa é de extrema importância para a maturação e a reprodução do parasita e constitui-se em bom alvo para novos antimaláricos, uma vez que é encontrada somente em parasitas. Hemácias infectadas têm sua absorção modificada em relação aos eritrócitos não-infectados, conferindo seletividade a substâncias como lipídeos. O trabalho em questão propõe a síntese de antimetabólitos da serina, visando à inibição das enzimas fosfatidilserina síntase e serina descarboxilase, fundamentais para a biossíntese de fosfolipídeos de membrana desses parasitas.. Cinco derivados heterocíclicos da serine foram sintetizados: derivados diidroimidazólico, diidroxazólico, diidroxazínico, diidropirimidínico e diidrooxatiólico. Também, o transportador fosfolipídico com o ácido esteárico foi sintetizado. Os antimetabólitos serão acoplados a esse e outros fosfolipídeos, obtendo-se fármacos dirigidos específicos direcionados seletivamente a eritrócitos infectados. / According to the World Health Organization, Aids, malaria and tuberculosis are the three greatest infectious diseases in the world. Children are the most involved in those diseases. Extremely poor regions, as sub-Saharan, Africa, are the most affected. In the worst case scenario, one of the parasites that causes malaria, Plasmodium falciparum, become resistant to chloroquine and the current therapy. Besides, some drugs used in the mataria chemotherapy are very toxic, showing many side effects, and compromising the treatment. This is a big challenge and facing it requires new strategies.. The development of chemotherapeutic has been inspired in biochemical differences between the parasite and the host. Plasmodíum falciparum needs to biosynthesize phospholipids for their membrane. These phospholipids are very important to the maturation and reproduction of the parasite and occur only in it.. This makes the phospholipids biosynthesis a good target for new and specific antimalarial drug design. Infected red blood cell shows modified permeation, allowing the lipids to be freely transported, what is not usual in the non-infected red blood cells. This said, in the present work the design and synthesis of serine metabolic inhibitors, using the bioisosteric strategy, have been proposed. The inhibition of the phosphatidylserine biosynthesis, an important phospholipid, is expected. These inhibitors will be linked to phospholipids, to promote the selective permeation to the infected red-blood cell.. These inhibitors will be linked to phospholipids, to promote the selective permeation to the infected redblood cell. In the present work five heterocyclic serine inhibitors: diidroimidazolic, diidroxazolic, diidroxazinico, diidropyriminic and diidroxatiolic. Also synthesized a phospholipid to be connected to the heterocyclic inhibitors. Antimaláricos (Planejamento;Síntese) Antimetabólitos Fármacos dirigidos Fosfolipídieos Malária (Quimioterapia) Planejamento de fármacos Serina Antimalarials (Planning Antimetabolic drugs Malaria (Chemotherapy) Phospholipids Planning drugs Serine Synthesis) Targeted drugs
8	Antimaláricos potenciais: planejamento e síntese de fármacos dirigidos de antimetabólitos de serina / Potential antimalarials: planning and synthesis of drugs directed serine antimetabolites Matsutani, Guilherme Costa 02 December 2008 (has links) De acordo com a Organização Mundial da Saúde, AIDS,malária e tuberculose são as três maiores doenças infectantes do mundo, atingindo principalmente crianças. Regiões paupérrimas e de clima tropical, como a África sub-saariana, são as mais atingidas. Este quadro agrava-se com a disseminação de cepas do Plasmodium falciparum resistentes à cloroquina e multi-resistentes.Além disso, alguns fármacos utilizados na terapêutica da malária apresentam vários efeitos adversos, comprometendo o tratamento. Trata-se de um grande desafio e o seu enfrentamento requer estratégias. O desenvolvimento de novos quimioterápicos deve fundamentar-se em diferenças bioquímicas e morfológicas entre as células do hospedeiro e do parasita. A biossíntese de fosfolipídeos de membrana em parasitas do grupo Apicomplexa é de extrema importância para a maturação e a reprodução do parasita e constitui-se em bom alvo para novos antimaláricos, uma vez que é encontrada somente em parasitas. Hemácias infectadas têm sua absorção modificada em relação aos eritrócitos não-infectados, conferindo seletividade a substâncias como lipídeos. O trabalho em questão propõe a síntese de antimetabólitos da serina, visando à inibição das enzimas fosfatidilserina síntase e serina descarboxilase, fundamentais para a biossíntese de fosfolipídeos de membrana desses parasitas.. Cinco derivados heterocíclicos da serine foram sintetizados: derivados diidroimidazólico, diidroxazólico, diidroxazínico, diidropirimidínico e diidrooxatiólico. Também, o transportador fosfolipídico com o ácido esteárico foi sintetizado. Os antimetabólitos serão acoplados a esse e outros fosfolipídeos, obtendo-se fármacos dirigidos específicos direcionados seletivamente a eritrócitos infectados. / According to the World Health Organization, Aids, malaria and tuberculosis are the three greatest infectious diseases in the world. Children are the most involved in those diseases. Extremely poor regions, as sub-Saharan, Africa, are the most affected. In the worst case scenario, one of the parasites that causes malaria, Plasmodium falciparum, become resistant to chloroquine and the current therapy. Besides, some drugs used in the mataria chemotherapy are very toxic, showing many side effects, and compromising the treatment. This is a big challenge and facing it requires new strategies.. The development of chemotherapeutic has been inspired in biochemical differences between the parasite and the host. Plasmodíum falciparum needs to biosynthesize phospholipids for their membrane. These phospholipids are very important to the maturation and reproduction of the parasite and occur only in it.. This makes the phospholipids biosynthesis a good target for new and specific antimalarial drug design. Infected red blood cell shows modified permeation, allowing the lipids to be freely transported, what is not usual in the non-infected red blood cells. This said, in the present work the design and synthesis of serine metabolic inhibitors, using the bioisosteric strategy, have been proposed. The inhibition of the phosphatidylserine biosynthesis, an important phospholipid, is expected. These inhibitors will be linked to phospholipids, to promote the selective permeation to the infected red-blood cell.. These inhibitors will be linked to phospholipids, to promote the selective permeation to the infected redblood cell. In the present work five heterocyclic serine inhibitors: diidroimidazolic, diidroxazolic, diidroxazinico, diidropyriminic and diidroxatiolic. Also synthesized a phospholipid to be connected to the heterocyclic inhibitors. Antimalarials (Planning Antimaláricos (Planejamento;Síntese) Antimetabolic drugs Antimetabólitos Fármacos dirigidos Fosfolipídieos Malaria (Chemotherapy) Malária (Quimioterapia) Phospholipids Planejamento de fármacos Planning drugs Serina Serine Synthesis) Targeted drugs
9	TARGETED DELIVERY OF BONE ANABOLICS TO BONE FRACTURES FOR ACCELERATED HEALING Jeffery J H Nielsen (8787002) 21 June 2022 (has links) <div>Delayed fracture healing is a major health issue involved with aging. Therefore, strategies to improve the pace of repair and prevent non-union are needed in order to improve patient outcomes and lower healthcare costs. In order to accelerate bone fracture healing noninvasively, we sought to develop a drug delivery system that could safely and effectively be used to deliver therapeutics to the site of a bone fracture. We elected to pursue the promising strategy of using small-molecule drug conjugates that deliver therapeutics to bone in an attempt to increase the efficacy and safety of drugs for treating bone-related diseases.</div><div>This strategy also opened the door for new methods of administering drugs. Traditionally, administering bone anabolic agents to treat bone fractures has relied entirely on local surgical application. However, because it is so invasive, this method’s use and development has been limited. By conjugating bone anabolic agents to bone-homing molecules, bone fracture treatment can be performed through minimally invasive subcutaneous administration. The exposure of raw hydroxyapatite that occurs with a bone fracture allows these high-affinity molecules to chelate the calcium component of hydroxyapatite and localize primarily to the fracture site.</div><div>Many bone-homing molecules (such as bisphosphonates and tetracycline targeting) have been developed to treat osteoporosis. However, many of these molecules have toxicity associated with them. We have found that short oligopeptides of acidic amino acids can localize to bone fractures with high selectivity and with very low toxicity compared to bisphosphonates and tetracyclines.</div><div>We have also demonstrated that these molecules can be used to target peptides of all chemical classes: hydrophobic, neutral, cationic, anionic, short, and long. This ability is particularly useful because many bone anabolics are peptidic in nature. We have found that acidic oligopeptides have better persistence at the site of the fracture than bisphosphonate-targeted therapeutics. This method allows for a systemic administration of bone anabolics to treat bone fractures, which it achieves by accumulating the bone anabolic at the fracture site. It also opens the door for a new way of treating the prevalent afflictions of broken bones and the deaths associated with them.</div><div>We further developed this technology by using it to deliver anabolic peptides derived from growth factors, angiogenic agents, neuropeptides, and extracellular matrix fragments. We found several promising therapeutics that accelerated the healing of bone fractures by improving the mineralization of the callus and improving the overall strength. We optimized the performance of these molecules by improving their stability, targeting ligands, linkers, dose, and dosing frequency.</div><div>We also found that these therapeutics could be used to accelerate bone fracture repair even in the presence of severe comorbidities (such as diabetes and osteoporosis) that typically slow the repair process. We found that, unlike the currently approved therapeutic for fracture healing (BMP2), our therapeutics improved functionality and reduced pain in addition to strengthening the bone. These optimized targeted bone anabolics were not only effective at healing bone fractures but they also demonstrated that they could be used to speed up spinal fusion. Additionally, we demonstrated that acidic oligopeptides have potential to be used to treat other bone diseases with damaged bone.</div><div>With these targeted therapeutics, we no longer have to limit bone fracture healing to casts or invasive surgeries. Rather, we can apply these promising therapeutics that can be administered non-invasively to augment existing orthopedic practices. As these therapeutics move into clinical development, we anticipate that they will be able to reduce the immobilization time that is the source of so many of the deadly complications associated with bone fracture healing, particularly in the elderly.</div> Genetics not elsewhere classified Nanobiotechnology Animal behaviour Clinical microbiology Endocrinology Nanomedicine Regenerative medicine (incl. stem cells) Solid state chemistry Molecular medicine Proteins and peptides Solution chemistry Radiation and matter Biomaterials Biomechanical engineering bone fracture healing Anabolic Agents/pharmacology Targeted Drug DeliveryDesign Bone fracture targeted drugs Bone theapeutics targeted therapies Growth factors Neuropepetides Extracellular matrix Extracellular matrix fragments spinal fusion Angiogensis Acidic oligopeptides osteoporosic fractures diabetic bone fractures Integrin alpha 5 Acelerated Bone fracture healing Hydroxyapatite Hydroxyapatite targeting Targeting peptides Peptide drugs osteomyelitis (OM) Rheumatoid arthritis Bone fractures osteogenic therapies osteotropic osteotropic nanomedicines osteoinductive capacity Molecular Medicine Organic Chemistry Proteins and Peptides Radiochemistry Solid State Chemistry Solution Chemistry Biochemistry Animal Behaviour Biological Engineering Biotechnology Genetics Medicine Pharmacology Biomaterials Biomechanical Engineering Biomechanics Endocrinology Nanobiotechnology Nanomedicine

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