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1.
Anticancer Res ; 40(1): 109-119, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892559

RESUMO

BACKGROUND/AIM: Although molecular targeting therapy is an attractive treatment for cancer, resistance eventually develops in most cases. Here, we evaluated chemotherapeutic efficacy on non-small cell lung cancer (NSCLC) with acquired resistance to epidermal growth factor receptor inhibitors mechanistically. MATERIALS AND METHODS: Antitumor effects of taxotere were evaluated using multiple models, including xenograft, and patient-derived models developed from adenocarcinoma cancer patients. Protein expressions were analyzed after drug treatment. RESULTS: Taxotere inhibited tumor growth of NSCLC cells harboring drug resistance, and reduced the expression of phosphorylated MET proto-oncogene, receptor tyrosine kinase (MET). A tumor-inhibitory effect of taxotere was also demonstrated in vivo in xenografts in mice, patient-derived primary lung tumor cells and patient-derived xenograft with concomitant repression of phosphorylated MET expression. Chemotherapeutic and MET-targeting drug exhibited a synergistic cell growth-inhibitory effect. CONCLUSION: These results suggest that the anticancer drug taxane may be an adjuvant for lung tumors exhibiting enhanced signaling of MET networks.


Assuntos
Antineoplásicos/farmacologia , Docetaxel/farmacologia , Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Animais , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Adv Exp Med Biol ; 1232: 145-153, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893405

RESUMO

The aim of the paper is to discuss what currently is feasible clinically to measure the level of oxygen and how that measurement can be clinically useful. Because oxygen in tissues is quite heterogeneous and all methods of measurement can only provide an average across heterogeneities at some spatial and temporal resolution, the values that are obtained may have limitations on their clinical utility. However, even if such limitations are significant, if one utilizes repeated measurements and focuses on changes in the measured levels, rather than 'absolute levels', it may be possible to obtain very useful clinical information. While these considerations are especially pertinent in cancer, they also pertain to most other types of pathology.


Assuntos
Oximetria , Oxigênio , Espectroscopia de Ressonância de Spin Eletrônica , Humanos , Neoplasias/metabolismo , Oximetria/métodos , Oxigênio/análise , Oxigênio/metabolismo
3.
Adv Exp Med Biol ; 1232: 155-168, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893406

RESUMO

The success of treatment for malignancies, especially those undergoing radiation therapy or chemotherapy, has long been recognized to depend on the degree of hypoxia in the tumor. In addition to the prognostic value of knowing the tumor's initial level of hypoxia, assessing the tumor oxygenation during standard therapy or oxygen-related treatments (such as breathing oxygen-enriched gas mixtures or taking drugs that can increase oxygen supply to tissues) can provide valuable data to improve the efficacy of treatments. A series of early clinical studies of tumors in humans are ongoing at Dartmouth and Emory using electron paramagnetic resonance (EPR) oximetry to assess tumor oxygenation, initially and over time during either natural disease progression or treatment. This approach has the potential for reaching the long-sought goal of enhancing the effectiveness of cancer therapy. In order to effectively reach this goal, we consider the validity of the practical and statistical assumptions when interpreting the measurements made in vivo for patients undergoing treatment for cancer.


Assuntos
Neoplasias , Oximetria , Oxigênio , Hipóxia Tumoral , Espectroscopia de Ressonância de Spin Eletrônica , Humanos , Neoplasias/metabolismo , Oxigênio/metabolismo
4.
J Enzyme Inhib Med Chem ; 35(1): 265-279, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31790602

RESUMO

Benzothiazole (BTA) belongs to the heterocyclic class of bicyclic compounds. BTA derivatives possesses broad spectrum biological activities such as anticancer, antioxidant, anti-inflammatory, anti-tumour, antiviral, antibacterial, anti-proliferative, anti-diabetic, anti-convulsant, analgesic, anti-tubercular, antimalarial, anti-leishmanial, anti-histaminic and anti-fungal among others. The BTA scaffolds showed a crucial role in the inhibition of the metalloenzyme carbonic anhydrase (CA). In this review an extensive literature survey over the last decade discloses the role of BTA derivatives mainly as anticancer agents. Such compounds are effective against various types of cancer cell lines through a multitude of mechanisms, some of which are poorly studied or understood. The inhibition of tumour associated CAs by BTA derivatives is on the other hand better investigated and such compounds may serve as anticancer leads for the development of agents effective against hypoxic tumours.


Assuntos
Antineoplásicos/farmacologia , Benzotiazóis/farmacologia , Neoplasias/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Benzotiazóis/síntese química , Benzotiazóis/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Neoplasias/metabolismo , Neoplasias/patologia , Relação Estrutura-Atividade
5.
Biosci Biotechnol Biochem ; 84(1): 31-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31794330

RESUMO

4-(2-Hydroxyphenethyl)-2,6-dimethoxyphenol, a bibenzyl, was isolated from the leaves of Empetrum nigrum var. japonicum, collected from Mount Tateyama. Japanese rock ptarmigans frequently eat the leaves and fruits of this plant. The structure of the bibenzyl was confirmed by NMR spectroscopic analysis and fully characterized. A synthesis of this compound was accomplished by coupling 2-hydroxyphenylacetic acid with syringaldehyde, decarboxylation of the resultant isoaurones, and hydrogenation of the double bond in the corresponding stilbene. This compound displayed cytotoxic activity against human cancer cells (HCT116 and Hela cells) and leukemia cells (HL-60 cells). The present study suggests that this plant serves as a source of biologically active natural products. Also, our findings provide information on the secondary metabolites in the diet of Japanese rock ptarmigans.


Assuntos
Bibenzilas/síntese química , Bibenzilas/farmacologia , Ericaceae/química , Extratos Vegetais/síntese química , Extratos Vegetais/farmacologia , Bacillus subtilis/efeitos dos fármacos , Bibenzilas/química , Bibenzilas/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Células HCT116 , Células HL-60 , Células HeLa , Humanos , Japão , Espectroscopia de Ressonância Magnética , Conformação Molecular , Neoplasias/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Pirogalol/análogos & derivados , Pirogalol/química
6.
Cell Physiol Biochem ; 53(S1): 52-62, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31854954

RESUMO

Kv1.3 is a voltage gated potassium channel located in the plasma membrane, as well as at intracellular levels, such as mitochondria (mitoKv1.3), nucleus and Golgi apparatus. The plasma membrane channel has been shown to be important for cell proliferation, while the mitochondrial counterpart has been related to modulation of cell death. Moreover, altered expression of Kv1.3 was observed in various tumors and Kv1.3 seems to be involved in development and progression of various cancerous forms. Recent experimental evidences have proved that pharmacological inhibition of the mitoKv1.3 succeeded in reducing up to 90% of tumor volume in vivo in orthotopic mouse model. Furthermore, mitoKv1.3 modulation could impact on cell proliferation as well as on regulation of intracellular signaling pathways. Indeed, the treatment with sub-lethal doses of mitoKv1.3 inhibitors can downregulate Wnt-ß catenin signaling by reducing mitochondrial ATP production and triggering ER-stress. In this review, we describe the role of the mitoKv1.3 in cell death, cancer and intracellular signaling. We will discuss how pharmacological modulation of mitochondrial potassium fluxes impact on mitochondrial membrane potential, reactive oxygen species production and ATP synthesis. All these changes in mitochondrial fitness are related to cell proliferation as well as to cell death and finally on cancer development and progression, so Kv1.3 (and mitoKv1.3) could be now considered a new oncological target.


Assuntos
Canal de Potássio Kv1.3/metabolismo , Mitocôndrias/metabolismo , Neoplasias/metabolismo , Animais , Apoptose , Proliferação de Células , Estresse do Retículo Endoplasmático , Canal de Potássio Kv1.3/antagonistas & inibidores , Canal de Potássio Kv1.3/genética , Neoplasias/patologia , Interferência de RNA , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
7.
Cell Physiol Biochem ; 53(S1): 63-78, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31860207

RESUMO

Mitochondria play a central role in cancer development, by contributing to most of the classical hallmarks of cancer, including sustained proliferation, metabolic re-programming, apoptosis resistance, invasion and induction of angiogenesis [1]. In addition, mitochondria affect also the function of anti- and pro-tumoral immune cells in the tumor microenvironment. Mitochondria harbor a plethora of regulated ion channels whose function is related to ion/ metabolite transport and to fine-tuning of mitochondrial membrane potential as well as of reactive oxygen species release. As a consequence, growing evidence link ion channels located both in the outer and inner mitochondrial membranes to several cancer hallmarks. The present review summarizes our recent knowledge about the participation and role of mitochondrial channels leading to acquisition of cancer hallmarks and thus to cancer progression.


Assuntos
Canais Iônicos/metabolismo , Mitocôndrias/patologia , Neoplasias/patologia , Animais , Apoptose , Proliferação de Células , Progressão da Doença , Humanos , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Membranas Mitocondriais/patologia , Neoplasias/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia
9.
Biochemistry (Mosc) ; 84(11): 1233-1246, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31760914

RESUMO

Cellular redox homeostasis involves a combination of redox processes and corresponding regulatory systems and represents an important factor ensuring cell viability. Redox-dependent regulation of cellular processes is a multi-level system including not only proteins and enzyme complexes, but also non-coding RNAs, among which an important role belongs to microRNAs. The review focuses on the involvement of miRNAs in the redox-dependent regulation of both ROS (reactive oxygen species)-generating enzymes and antioxidant enzymes with special emphasis on the effects of miRNAs on redox-dependent processes in tumor cells. The impact of ROS on the miRNA expression and the role of the ROS/miRNA feedback regulation in the cell redox state are discussed.


Assuntos
MicroRNAs/metabolismo , Animais , Humanos , MicroRNAs/química , Neoplasias/metabolismo , Neoplasias/patologia , Oxirredução , Estresse Oxidativo , Oxirredutases/metabolismo , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo
10.
Biochemistry (Mosc) ; 84(9): 1047-1056, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31693464

RESUMO

Plant hormones produce cytotoxic effect on human cells and can trigger the processes unrelated to cell death, e.g., biosynthetic system stress. The goal of this study was to investigate activation of the endoplasmic reticulum (ER) stress by jasmonic acid (JA) and to distinguish between the responses of cultured immortalized non-tumorigenic HaCaT cells and epidermoid carcinoma A431 cells to this plant hormone. JA was used in the concentration of 2 mM, as it suppressed cell proliferation in both cell lines. We analyzed expression of genes associated with the activation of ER stress (GRP78, ATF4, CHOP), the structure of the ER and Golgi complex, and synthetic processes in the HaCaT and A431 cell lines. JA induced expression of genes responsible for the activation of ER stress and caused hypertrophic changes in the Golgi complex in both cell lines. However, the patterns of gene expression in the HaCaT and A431 cells were different, and higher levels of involucrin synthesis were observed in A431 but not in HaCaT cells, suggesting that JA activated differentiation of the tumor A431 cells only. Therefore, JA induced ER stress in both cell lines, but the consequences of ER stress were different for the epidermal immortalized non-tumorigenic and tumor cells.


Assuntos
Ciclopentanos/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Epidérmicas/efeitos dos fármacos , Células Epidérmicas/patologia , Neoplasias/patologia , Oxilipinas/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Células Epidérmicas/citologia , Humanos , Neoplasias/metabolismo , Relação Estrutura-Atividade
11.
Biochemistry (Mosc) ; 84(10): 1117-1128, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31694508

RESUMO

According to modern concepts, tumor formation is associated with impairments in the structure of protooncogenes and/or deactivation of suppressor genes, regardless of the nature of carcinogenic factor. As a consequence, unregulated oncoproteins activate extracellular proteases, resulting in the destruction of the extracellular matrix, which facilitates cell invasion, deterioration of the cell-cell contacts, and metastasis. Tumor development requires activation of certain transcription factors; however, many oncoproteins are not transcription factors. It can be assumed that these oncoproteins are not the ultimate effectors of tumor development, but rather transmitters of the carcinogenic signal to the transcription factors promoting tumorigenesis. Here, we describe the mechanisms of carcinogenesis caused by various oncogenes/oncoproteins. We conclude that the common feature of these mechanisms is stimulation of aerobic glycolysis (Warburg effect) regulated, as a rule, through the activation of the HIFα transcription factor. The role of aerobic glycolysis at the early stages of carcinogenesis is discussed.


Assuntos
Carcinogênese/metabolismo , Glicólise , Neoplasias/metabolismo , Proteínas Oncogênicas/metabolismo , Animais , Carcinogênese/genética , Humanos , Neoplasias/genética , Proteínas Oncogênicas/genética
12.
Biochemistry (Mosc) ; 84(10): 1129-1142, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31694509

RESUMO

Metabolic reprogramming is one of the central features of transformed cells. Elucidation of interactions between oncogenic signaling and cell metabolic processes has become the basis for extensive studies of metabolism reprogramming in tumor tissue. The review summarizes the key results of studies on the catabolic and anabolic rearrangements in tumor cells with special emphasis on carbohydrate, lipid, amino acid, and acetate metabolism determining the cancer phenotype of cells.


Assuntos
Neoplasias/metabolismo , Neoplasias/patologia , Humanos , Fenótipo
13.
Medicine (Baltimore) ; 98(45): e17529, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702612

RESUMO

BACKGROUND: A number of studies have attempted to determine the prognostic value of T-cell lymphoma invasion and metastasis-inducing factor 1 (Tiam1) in patients with solid cancers, but the reported results were of inconsistency. Thus, we performed a systematic review and meta-analysis to exhaustively evaluate the prognostic role of Tiam1 expression in patients with solid cancers. METHODS: We retrieved literature published in between 1994 and April 22th, 2019 through searching PubMed, Web of Science and China national knowledge infrastructure (CNKI). Hazard ratios (HRs) coupled with 95% confidence intervals (95% CIs) were used to assess the relationship of Tiam1 expression and overall survival (OS), and disease-free survival (DFS). RESULTS: A total of 2647 patients with solid cancers in 20 studies were enrolled in our meta-analysis eventually. The pooled results showed that Tiam1 high expression was closely correlated with poor OS (HR = 2.17, 95% CI: 1.80-2.61, P = .000) and DFS (pooled HR = 1.95, 95% CI = 1.58-2.40, P = .000). Moreover, our subgroup analysis and sensitivity analysis demonstrated the reliability and stability of our pooled results. CONCLUSION: In conclusion, this meta-analysis confirmed that Tiam1 higher expression positively correlated with OS and DFS, suggesting that Tiam1 may act as a valuable prognostic predictor and therapeutic target for patients with solid cancers. Nevertheless, in future more homogeneous and prospective studies should be performed to further support our findings.


Assuntos
Neoplasias/metabolismo , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T/metabolismo , Regulação para Cima , Biomarcadores Tumorais/metabolismo , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Estudos Prospectivos
15.
Life Sci ; 237: 116952, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31622608

RESUMO

Cancer stem cells (CSC) constitute a small area of the tumor mass and are characterized by self-renewal, differentiation and the ability to promote the development of secondary chemo-resistant tumors. Self-renewal of CSCs is regulated through various signaling pathways including Hedgehog, Notch, and Wnt/ß-catenin pathways. A few surface markers have been identified, which provide a means of targeting CSCs according to tumor type. Depending on the proximity of CSCs to the tumor hypoxic niche, hypoxia-inducible factors (HIFs) can play a critical role in modulating several CSC-related characteristics. For instance, the upregulation of HIF-1 and HIF-2 at tumor sites, which correlates with the expansion of CSCs and poor cancer prognosis, has been demonstrated. In this review, we will discuss the mechanisms by which hypoxia enhances the development of CSCs in the tumor microenvironment. Targeting HIFs in combination with other common therapeutics is pre-requisite for effective eradication of CSCs.


Assuntos
Antineoplásicos/farmacologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Hipóxia/fisiopatologia , Neoplasias/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Animais , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia
16.
Cell Biochem Biophys ; 77(4): 293-308, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31598831

RESUMO

Appropriate mechanical forces on cells are vital for normal cell behaviour and this review discusses the possibility that tumour initiation depends partly on the disruption of the normal physical architecture of the extracellular matrix (ECM) around a cell. The alterations that occur thence promote oncogene expression. Some questions, that are not answered with certainty by current consensus mechanisms of tumourigenesis, are elegantly explained by the triggering of tumours being a property of the physical characteristics of the ECM, which is operative following loading of the tumour initiation process with a relevant gene variant. Clinical observations are consistent with this alternative hypothesis which is derived from studies that have, together, accumulated an extensive variety of data incorporating biochemical, genetic and clinical findings. Thus, this review provides support for the view that the ECM may have an executive function in induction of a tumour. Overall, reported observations suggest that either restoring an ECM associated with homeostasis or targeting the related signal transduction mechanisms may possibly be utilised to modify or control the early progression of cancers. The review provides a coherent template for discussing the notion, in the context of contemporary knowledge, that tumourigenesis is an alliance of biochemistry, genetics and biophysics, in which the physical architecture of the ECM may be a fundamental component. For more definitive clarification of the concept there needs to be a phalanx of experiments conceived around direct questions that are raised by this paper.


Assuntos
Carcinogênese/metabolismo , Neoplasias/patologia , Envelhecimento , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Humanos , Mutação , Neoplasias/metabolismo , Transdução de Sinais , Estresse Mecânico
18.
Cancer Immunol Immunother ; 68(11): 1881-1889, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31595324

RESUMO

Adoptive cell transfer (ACT) using T cell receptor (TCR) gene-modified T cells is an exciting and rapidly evolving field. Numerous preclinical and clinical studies have demonstrated various levels of feasibility, safety, and efficacy using TCR-engineered T cells to treat cancer and viral infections. Although evidence suggests their use can be effective, to what extent and how to improve these therapeutics are still matters of investigation. As TCR affinity has been generally accepted as the central role in defining T cell specificity and sensitivity, selection for and generation of high affinity TCRs has remained a fundamental approach to design more potent T cells. However, traditional methods for affinity-enhancement by random mutagenesis can induce undesirable cross-reactivity causing on- and off-target adverse events, generate exhausted effectors by overstimulation, and ignore other kinetic and cellular parameters that have been shown to impact antigen specificity. In this Focussed Research Review, we comment on the preclinical and clinical potential of TCR gene-modified T cells, summarize our contributions challenging the role TCR affinity plays in antigen recognition, and explore how structure-guided design can be used to manipulate antigen specificity and TCR cross-reactivity to improve the safety and efficacy of TCR gene-modified T cells used in ACT.


Assuntos
Citotoxicidade Imunológica/imunologia , Genes Codificadores dos Receptores de Linfócitos T/imunologia , Imunoterapia , Neoplasias/terapia , Linfócitos T/imunologia , Linfócitos T/transplante , Animais , Especificidade de Anticorpos , Reações Cruzadas , Genes Codificadores dos Receptores de Linfócitos T/genética , Humanos , Neoplasias/imunologia , Neoplasias/metabolismo , Especificidade do Receptor de Antígeno de Linfócitos T , Linfócitos T/metabolismo
19.
Medicine (Baltimore) ; 98(40): e17439, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577764

RESUMO

BACKGROUND: Speckle-type POZ protein (SPOP) has recently been reported as a prognostic tumor biomarker. However, the predictive value of SPOP remains controversial in human cancers. The current meta-analysis was performed to obtain a comprehensive evaluation of the relationship between SPOP expression and prognosis of cancer patients. METHODS: Embase, Pubmed, Web of Science, and Chinese Biomedical Literature database were systematically searched up to January 2, 2019. The pooled hazard ratios (HRs) and/or pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to quantitatively assess the relationship of SPOP expression with prognosis and lymph node metastasis (LNM). RESULTS: A total of 9 studies with 928 patients were included in this meta-analysis. The results showed that low SPOP expression was significantly related to poor overall survival (high/low: HR = 0.55; 95% CI: 0.38-0.79, P = .001), especially for digestive system cancers (high/low: HR = 0.46; 95% CI: 0.27-0.78, P = .003). However, SPOP expression did not affect progression-free survival in cancer patients (high/low: HR = 2.07; 95% CI: 0.16-26.70, P = .578). Additionally, the association between SPOP overexpression and LNM was positive in patients with clear cell renal cell carcinoma (ccRCC) (OR = 5.26; 95% CI: 1.66-16.68, P = .005) but negative in cancer patients without ccRCC (OR = 0.36; 95% CI: 0.21-0.62, P < .001). CONCLUSION: Decreased SPOP expression could predict poor prognosis of cancer patients, suggesting that SPOP protein may be a useful prognostic biomarker in cancer patients.


Assuntos
Metástase Linfática/diagnóstico , Neoplasias/diagnóstico , Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Humanos , Neoplasias/mortalidade , Valor Preditivo dos Testes , Prognóstico
20.
Curr Top Med Chem ; 19(19): 1712-1733, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31659944

RESUMO

During the early preclinical phase, from hit identification and optimization to a lead compound, several medicinal chemistry strategies can be used to improve potency and/or selectivity. The conformational restriction is one of these approaches. It consists of introducing some specific structural constraints in a lead candidate to reduce the overall number of possible conformations in order to favor the adoption of a bioactive conformation and, as a consequence, molecular recognition by the target receptor. In this work, we focused on the application of the conformational restriction strategy in the last five years for the optimization of hits and/or leads of several important classes of therapeutic targets in the drug discovery field. Thus, we recognize the importance of several kinase inhibitors to the current landscape of drug development for cancer therapy and the use of G-protein Coupled Receptor (GPCR) modulators. Several other targets are also highlighted, such as the class of epigenetic drugs. Therefore, the possibility of exploiting conformational restriction as a tool to increase the potency and selectivity and promote changes in the intrinsic activity of some ligands intended to act on many different targets makes this strategy of structural modification valuable for the discovery of novel drug candidates.


Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Antineoplásicos/química , Química Farmacêutica , Descoberta de Drogas , Humanos , Estrutura Molecular , Neoplasias/metabolismo , Neoplasias/patologia , Receptores Acoplados a Proteínas-G/metabolismo
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