Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy ...Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy for cancers has been developed and achieved enormous clinical effectiveness by transforming some previously deadly malignancies into chronically manageable conditions, but cure problem still remains. This mini review outlined the current status of anticancer drugs development and hinted the opinions of how to further increase the accuracy and efficacy of discovery for cancer treatment.展开更多
Off-label use is defined by the prescription of a marketed drug outside the conditions described in the summary of product characteristics.In oncology,off-label prescribing of targeted therapies may occur in patients ...Off-label use is defined by the prescription of a marketed drug outside the conditions described in the summary of product characteristics.In oncology,off-label prescribing of targeted therapies may occur in patients with other tumor types expressing the same target.Agents associated to phenotypic approaches such as therapies against the tumoral vasculature(anti-angiogenic drugs) and new immunotherapies(checkpoint inhibitors) also carry the potential of alternative indications or combinations.Off-label use of targeted therapies is little documented and appears to be in the same range than that regarding older drugs with wide variations among agents.When compared with older agents,off-label use of targeted therapies is probably more rational through tumoral genotyping but is faced with a limited clinical support,reimbursement challenges related to the very high pricing and the cost of genotyping or molecular profiling,when applicable.展开更多
Dihydroorotate dehydrogenase(DHODH)is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune diseases.This study presents the identifi...Dihydroorotate dehydrogenase(DHODH)is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune diseases.This study presents the identification of a potent DHODH inhibitor by proteomic profiling.Cell-based screening revealed that NPD723,which is reduced to H-006 in cells,strongly induces myeloid differentiation and inhibits cell growth in HL-60 cells.H-006 also suppressed the growth of various cancer cells.Proteomic profiling of NPD723-treated cells in ChemProteoBase showed that NPD723 was clustered with DHODH inhibitors.H-006 potently inhibited human DHODH activity in vitro,whereas NPD723 was approximately 400 times less active than H-006.H-006-induced cell death was rescued by the addition of the DHODH product orotic acid.Moreover,metabolome analysis revealed that H-006 treatment promotes marked accumulation of the DHODH substrate dihydroorotic acid.These results suggest that NPD723 is reduced in cells to its active metabolite H-006,which then targets DHODH and suppresses cancer cell growth.Thus,H-006-related drugs represent a potentially powerful treatment for cancer and other diseases.展开更多
In the last few decades numbers of review and research articles have been published on niosomes. This shows the relevant interest of academias & researchers in niosomes because of the advantages sponsored by them ...In the last few decades numbers of review and research articles have been published on niosomes. This shows the relevant interest of academias & researchers in niosomes because of the advantages sponsored by them over other colloidal drug delivery systems. Niosomes formation occurs when non-ionic surfactant vesicles assemble themselves. Various antineoplastic agents are used in chemotherapy, but they have some drawbacks that these agents cause cell death in normal tissues as well. There are two approaches to overcome this limitation. First, to modify the structure of existing drugs, but this will not possible because it changes the properties of drugs. Second, the development of nano-carriers like liposomes, dendrimers, nanoparticles, niosomes et al. Among all, niosomes (non-ionic surfactant vesicles) have more advantages besides all nano-carriers. Drugs either hydrophilic in nature or hydrophobic in nature, both can be incorporated in niosomes. And by embedding specific ligands over vesicular surface enables us to target the drug to specific cancer cells.展开更多
丝/苏氨酸蛋白激酶Akt(又名prote in k inase B)在多种人类肿瘤中存在表达或活性失调,并且Akt在调节肿瘤细胞生长、增殖,促进细胞侵袭和转移,促进新生血管生成,以及肿瘤细胞产生化疗、放疗耐受性中起着重要作用,因此,Akt已成为抗肿瘤药...丝/苏氨酸蛋白激酶Akt(又名prote in k inase B)在多种人类肿瘤中存在表达或活性失调,并且Akt在调节肿瘤细胞生长、增殖,促进细胞侵袭和转移,促进新生血管生成,以及肿瘤细胞产生化疗、放疗耐受性中起着重要作用,因此,Akt已成为抗肿瘤药物的潜在靶点。以Akt为靶点的药物开发已成为当前研究的热点。目前已开发出多种针对Akt,具有抗肿瘤活性的化合物,如API-2、Akt-I-1、Akt-I-2、DC IEL。这些化合物有可能对Akt异常的肿瘤有高选择性和高疗效,具有良好的应用前景。展开更多
文摘Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy for cancers has been developed and achieved enormous clinical effectiveness by transforming some previously deadly malignancies into chronically manageable conditions, but cure problem still remains. This mini review outlined the current status of anticancer drugs development and hinted the opinions of how to further increase the accuracy and efficacy of discovery for cancer treatment.
文摘Off-label use is defined by the prescription of a marketed drug outside the conditions described in the summary of product characteristics.In oncology,off-label prescribing of targeted therapies may occur in patients with other tumor types expressing the same target.Agents associated to phenotypic approaches such as therapies against the tumoral vasculature(anti-angiogenic drugs) and new immunotherapies(checkpoint inhibitors) also carry the potential of alternative indications or combinations.Off-label use of targeted therapies is little documented and appears to be in the same range than that regarding older drugs with wide variations among agents.When compared with older agents,off-label use of targeted therapies is probably more rational through tumoral genotyping but is faced with a limited clinical support,reimbursement challenges related to the very high pricing and the cost of genotyping or molecular profiling,when applicable.
基金supported by AMED Grants(Nos.JP16cm0106112 and JP16cm0106002)JSPS KAKENHI Grants(Nos.JP17H06412,18H05503,JP19K05744,JP20K05857,JP20H05620,JP21H04720,JP22H04922,and JP22K05363).
文摘Dihydroorotate dehydrogenase(DHODH)is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune diseases.This study presents the identification of a potent DHODH inhibitor by proteomic profiling.Cell-based screening revealed that NPD723,which is reduced to H-006 in cells,strongly induces myeloid differentiation and inhibits cell growth in HL-60 cells.H-006 also suppressed the growth of various cancer cells.Proteomic profiling of NPD723-treated cells in ChemProteoBase showed that NPD723 was clustered with DHODH inhibitors.H-006 potently inhibited human DHODH activity in vitro,whereas NPD723 was approximately 400 times less active than H-006.H-006-induced cell death was rescued by the addition of the DHODH product orotic acid.Moreover,metabolome analysis revealed that H-006 treatment promotes marked accumulation of the DHODH substrate dihydroorotic acid.These results suggest that NPD723 is reduced in cells to its active metabolite H-006,which then targets DHODH and suppresses cancer cell growth.Thus,H-006-related drugs represent a potentially powerful treatment for cancer and other diseases.
文摘In the last few decades numbers of review and research articles have been published on niosomes. This shows the relevant interest of academias & researchers in niosomes because of the advantages sponsored by them over other colloidal drug delivery systems. Niosomes formation occurs when non-ionic surfactant vesicles assemble themselves. Various antineoplastic agents are used in chemotherapy, but they have some drawbacks that these agents cause cell death in normal tissues as well. There are two approaches to overcome this limitation. First, to modify the structure of existing drugs, but this will not possible because it changes the properties of drugs. Second, the development of nano-carriers like liposomes, dendrimers, nanoparticles, niosomes et al. Among all, niosomes (non-ionic surfactant vesicles) have more advantages besides all nano-carriers. Drugs either hydrophilic in nature or hydrophobic in nature, both can be incorporated in niosomes. And by embedding specific ligands over vesicular surface enables us to target the drug to specific cancer cells.
文摘丝/苏氨酸蛋白激酶Akt(又名prote in k inase B)在多种人类肿瘤中存在表达或活性失调,并且Akt在调节肿瘤细胞生长、增殖,促进细胞侵袭和转移,促进新生血管生成,以及肿瘤细胞产生化疗、放疗耐受性中起着重要作用,因此,Akt已成为抗肿瘤药物的潜在靶点。以Akt为靶点的药物开发已成为当前研究的热点。目前已开发出多种针对Akt,具有抗肿瘤活性的化合物,如API-2、Akt-I-1、Akt-I-2、DC IEL。这些化合物有可能对Akt异常的肿瘤有高选择性和高疗效,具有良好的应用前景。
