NIH assistance for new therapeutic development: NIH-RAID Pilot Program

2009 ◽  
Vol 15 (1) ◽  
Author(s):  
David G Badman
Keyword(s):  
Gene Therapy ◽  
Monoclonal Antibodies ◽  
Natural Product ◽  
Small Molecule ◽  
Recombinant Proteins ◽  
Therapeutic Agents ◽  
Preclinical Development ◽  
Non Profit ◽  
Data Services ◽  
Therapeutic Development

The National Institutes of Health (NIH) wishes to alert the biotech/medical research community to an opportunity to obtain assistance in the development of new therapeutic agents. The NIH Roadmap has established a pilot programme, the NIH-Rapid Access to Interventional Development (RAID) Pilot, to make available, on a competitive basis, critical resources needed for the development of new small-molecule or natural product-derived therapeutic agents. This programme, part of the Translational Research component of Reengineering the Clinical Research Enterprise, uses resources of NCI's Developmental Therapeutics Program. Services provided depend upon the project and strength of the preliminary data. Services potentially available include bulk supply, GMP manufacturing, formulation, assay development suitable for pharmacokinetic testing, and animal toxicology. Assistance can also be provided in the regulatory process. Currently, animal efficacy studies and synthesis of recombinant proteins, monoclonal antibodies, or reagents for gene therapy are not supported. The NIH-RAID Pilot will, however, consider requests for services to support later-stage preclinical development of monoclonal antibodies, recombinant proteins, and gene therapy agents. Additionally, the NIH-RAID Pilot will now consider requests for the manufacture of small-molecule or natural product material for any clinical study. Proposals must originate from academic or non-profit investigators, but collaboration with industry partners is encouraged.

Pharmacotherapeutics of Biotechnology-Derived Products

1998 ◽  
Vol 11 (1) ◽  
pp. 54-71
Author(s):  
Peggy Bush
Keyword(s):  
Gene Therapy ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Small Molecules ◽  
Orphan Drug ◽  
Recombinant Proteins ◽  
Human Disease ◽  
Drug Status ◽  
Small Patient ◽  
Biotechnology Products

Biotechnology has contributed to important advances in the healthcare field. Products include various hormones, enzymes, cytokines, vaccines, and monoclonal antibodies, with use in diverse therapeutic areas. The majority of approved biotechnology-derived therapeutic products are recombinant proteins. Many have orphan drug status and, therefore, are used in relatively small patient populations. Newer generation biotechnology products are likely to include small molecules, gene therapy products, and increased numbers of vaccines and monoclonal antibody products. Biotechnology provides the means to develop diverse, innovative, and effective approaches to the prevention, treatment, and cure of human disease.

scholarly journals Monoclonal antibodies as therapeutic agents in oncology and antibody gene therapy

Cell Research ◽  
2007 ◽  
Vol 17 (2) ◽  
pp. 89-99 ◽  
Author(s):  
Qi Zhang ◽  
Guihua Chen ◽  
Xinyuan Liu ◽  
Qijun Qian
Keyword(s):  
Gene Therapy ◽  
Monoclonal Antibodies ◽  
Therapeutic Agents ◽  
Antibody Gene

scholarly journals Suprachoroidal Delivery of Small Molecules, Nanoparticles, Gene and Cell Therapies for Ocular Diseases

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 288
Author(s):  
Chen-rei Wan ◽  
Leroy Muya ◽  
Viral Kansara ◽  
Thomas A. Ciulla
Keyword(s):  
Drug Delivery ◽  
Gene Therapy ◽  
Small Molecules ◽  
Small Molecule ◽  
Viral Vector ◽  
Choroidal Melanoma ◽  
Therapeutic Agents ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Age Related

Suprachoroidal drug delivery technology has advanced rapidly and emerged as a promising administration route for a variety of therapeutic candidates, in order to target multiple ocular diseases, ranging from neovascular age-related macular degeneration to choroidal melanoma. This review summarizes the latest preclinical and clinical progress in suprachoroidal delivery of therapeutic agents, including small molecule suspensions, polymeric entrapped small molecules, gene therapy (viral and nonviral nanoparticles), viral nanoparticle conjugates (VNCs), and cell therapy. Formulation customization is critical in achieving favorable pharmacokinetics, and sustained drug release profiles have been repeatedly observed for multiple small molecule suspensions and polymeric formulations. Novel therapeutic agents such as viral and nonviral gene therapy, as well as VNCs, have demonstrated promise in animal studies. Several of these suprachoroidally-administered therapies have been assessed in clinical trials, including small molecule suspensions of triamcinolone acetonide and axitinib, viral vector RGX-314 for gene therapy, and VNC AU-011. With continued drug delivery research and optimization, coupled with customized drug formulations, suprachoroidal drug delivery may address large unmet therapeutic needs in ophthalmology, targeting affected tissues with novel therapies for efficacy benefits, compartmentalizing therapies away from unaffected tissues for safety benefits, and achieving durability to relieve the treatment burden noted with current agents.

scholarly journals Use of Transgenic Animals in Biotechnology: Prospects and Problems

Acta Naturae ◽  
2013 ◽  
Vol 5 (1) ◽  
pp. 33-46 ◽  
Author(s):  
O. G. Maksimenko ◽  
A. V. Deykin ◽  
Yu. M. Khodarovich ◽  
P. G. Georgiev
Keyword(s):  
Monoclonal Antibodies ◽  
Recombinant Proteins ◽  
Transgenic Animals ◽  
Therapeutic Agents ◽  
C1 Inhibitor ◽  
The Past ◽  
Human Proteins ◽  
Near Future

During the past two decades, there have been numerous attempts at using animals in order to produce recombinant human proteins and monoclonal antibodies. However, it is only recently that the first two therapeutic agents isolated from the milk of transgenic animals, C1 inhibitor (Ruconest) and antithrombin (ATryn), appeared on the market. This inspires hope that a considerable number of new recombinant proteins created using such technology could become available for practical use in the near future. In this review, the methods applied to produce transgenic animals are described and the advantages and drawbacks related to their use for producing recombinant human proteins and monoclonal antibodies are discussed.

Metabolism and Distribution of Novel Tumor Targeting Drugs In Vivo

2020 ◽  
Vol 21 (13) ◽  
pp. 996-1008
Author(s):  
Mengli Wang ◽  
Qiuzheng Du ◽  
Lihua Zuo ◽  
Peng Xue ◽  
Chao Lan ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Small Molecule ◽  
High Efficiency ◽  
Tumor Therapy ◽  
Research Progress ◽  
Future Research ◽  
Pharmacokinetic Parameters ◽  
Molecular Characteristics ◽  
Targeted Drugs

Background: As a new tumor therapy, targeted therapy is becoming a hot topic due to its high efficiency and low toxicity. Drug effects of targeted tumor drugs are closely related to pharmacokinetics, so it is important to understand their distribution and metabolism in vivo. Methods: A systematic review of the literature on the metabolism and distribution of targeted drugs over the past 20 years was conducted, and the pharmacokinetic parameters of approved targeted drugs were summarized in combination with the FDA's drug instructions. Targeting drugs are divided into two categories: small molecule inhibitors and monoclonal antibodies. Novel targeting drugs and their mechanisms of action, which have been developed in recent years, are summarized. The distribution and metabolic processes of each drug in the human body are reviewed. Results: In this review, we found that the distribution and metabolism of small molecule kinase inhibitors (TKI) and monoclonal antibodies (mAb) showed different characteristics based on the differences of action mechanism and molecular characteristics. TKI absorbed rapidly (Tmax ≈ 1-4 h) and distributed in large amounts (Vd > 100 L). It was mainly oxidized and reduced by cytochrome P450 CYP3A4. However, due to the large molecular diameter, mAb was distributed to tissues slowly, and the volume of distribution was usually very low (Vd < 10 L). It was mainly hydrolyzed and metabolized into peptides and amino acids by protease hydrolysis. In addition, some of the latest drugs are still in clinical trials, and the in vivo process still needs further study. Conclusion: According to the summary of the research progress of the existing targeting drugs, it is found that they have high specificity, but there are still deficiencies in drug resistance and safety. Therefore, the development of safer and more effective targeted drugs is the future research direction. Meanwhile, this study also provides a theoretical basis for clinical accurate drug delivery.

Targeting p53-MDM2 Interaction Using Small Molecule Inhibitors and the Challenges Needed to be Addressed

2019 ◽  
Vol 20 (11) ◽  
pp. 1091-1111 ◽  
Author(s):  
Maryam Zanjirband ◽  
Soheila Rahgozar
Keyword(s):  
Clinical Trials ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Tp53 Gene ◽  
Therapeutic Agents ◽  
Negative Regulator ◽  
Mdm2 Protein ◽  
Independent Effects ◽  
Small Hydrophobic ◽  
Targeted Therapeutic

MDM2 protein is the core negative regulator of p53 that maintains the cellular levels of p53 at a low level in normal cells. Mutation of the TP53 gene accounts for 50% of all human cancers. In the remaining malignancies with wild-type TP53, p53 function is inhibited through other mechanisms. Recently, synthetic small molecule inhibitors have been developed which target a small hydrophobic pocket on MDM2 to which p53 normally binds. Given that MDM2-p53 antagonists have been undergoing clinical trials for different types of cancer, this review illustrates different aspects of these new cancer targeted therapeutic agents with the focus on the major advances in the field. It emphasizes on the p53 function, regulation of p53, targeting of the p53-MDM2 interaction for cancer therapy, and p53-dependent and -independent effects of inhibition of p53-MDM2 interaction. Then, representatives of small molecule MDM2-p53 binding antagonists are introduced with a focus on those entered into clinical trials. Furthermore, the review discusses the gene signatures in order to predict sensitivity to MDM2 antagonists, potential side effects and the reasons for the observed hematotoxicity, mechanisms of resistance to these drugs, their evaluation as monotherapy or in combination with conventional chemotherapy or with other targeted therapeutic agents. Finally, it highlights the certainly intriguing questions and challenges which would be addressed in future studies.

An overview on interactions between natural product-derived β-glucan and small-molecule compounds

2021 ◽  
Vol 261 ◽  
pp. 117850
Author(s):  
Xiao-Hui Fang ◽  
Ming-Yue Zou ◽  
Fu-Quan Chen ◽  
Hui Ni ◽  
Shao-Ping Nie ◽  
...  
Keyword(s):  
Natural Product ◽  
Small Molecule
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