Synthesis, Structure–Activity Relationships, and in Vivo Efficacy of the Novel Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor 5-Chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) Currently in Phase 1 and Phase 2 Clinical Trials

2013 ◽  
Vol 56 (14) ◽  
pp. 5675-5690 ◽  
Author(s):  
Thomas H. Marsilje ◽  
Wei Pei ◽  
Bei Chen ◽  
Wenshuo Lu ◽  
Tetsuo Uno ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase 1 ◽  
The Novel ◽  
Phase 2 ◽  
In Vivo Efficacy ◽  
Anaplastic Lymphoma ◽  
Alk Inhibitor ◽  
Structure Activity ◽  
Phase 2 Clinical Trials

scholarly journals GNOSIS: Guidelines for neuro-oncology: Standards for investigational studies—reporting of phase 1 and phase 2 clinical trials

2005 ◽  
Vol 7 (4) ◽  
pp. 425-434 ◽  
Author(s):  
Susan M. Chang ◽  
Sharon L. Reynolds ◽  
Nicholas Butowski ◽  
Kathleen R. Lamborn ◽  
Jan C. Buckner ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase 1 ◽  
Phase 2 ◽  
Phase 2 Clinical Trials

scholarly journals Alzheimer’s disease: An overview of the current treatments

Bionatura ◽  
2019 ◽  
Vol 02 (Bionatura Conference Serie) ◽  
Author(s):  
Carolina Serrano-Larrea ◽  
David Clavijo-Calderón
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Therapy ◽  
Clinical Trials ◽  
Nerve Growth Factor ◽  
Phase 1 ◽  
Phase 2 ◽  
Adeno Associated Virus ◽  
The World ◽  
Phase 2 Clinical Trials

Alzheimer’s disease (AD) affects millions of people around the world and although there are treatments that help control symptoms and slow down the progress of the disease, there is still no cure. Current treatments include three acetylcholine inhibitors, a glutamate inhibitor and a combination of the two. Due to the failure of hundreds of clinical trials with monotherapies, multitarget treatments are currently being investigated that consider both brain and peripheral factors. Gene therapy is one of the most promising therapies to treat and prevent the development of AD. Nowadays, there is no available medical treatment based on gene therapy to treat AD; however, there are treatments in phase 1 and phase 2 clinical trials with promising results. In this review, we will focus on the most important gene therapy treatments, CERE-110 (adeno-associated virus AAV2-Nerve Growth Factor), Intracerebral AAV gene delivery of APOE2 and gene therapy using PPARγ-coactivator-1α(PGC-1α)

scholarly journals Immunogenicity of clinically relevant SARS-CoV-2 vaccines in nonhuman primates and humans

2021 ◽  
Vol 7 (12) ◽  
pp. eabe8065 ◽  
Author(s):  
P. J. Klasse ◽  
Douglas F. Nixon ◽  
John P. Moore
Keyword(s):  
Clinical Trials ◽  
Nonhuman Primates ◽  
Phase 1 ◽  
Phase 2 ◽  
Press Releases ◽  
Phase 3 ◽  
Virus Challenge ◽  
Efficacy Trials ◽  
Phase 2 Clinical Trials ◽  
Do So

Multiple preventive vaccines are being developed to counter the coronavirus disease 2019 pandemic. The leading candidates have now been evaluated in nonhuman primates (NHPs) and human phase 1 and/or phase 2 clinical trials. Several vaccines have already advanced into phase 3 efficacy trials, while others will do so before the end of 2020. Here, we summarize what is known of the antibody and T cell immunogenicity of these vaccines in NHPs and humans. To the extent possible, we compare how the vaccines have performed, taking into account the use of different assays to assess immunogenicity and inconsistencies in how the resulting data are presented. We also review the outcome of challenge experiments with severe acute respiratory syndrome coronavirus 2 in immunized macaques, while noting variations in the protocols used, including but not limited to the virus challenge doses. Press releases on the outcomes of vaccine efficacy trials are also summarized.

Clinical Drug Development for the Treatment of Pulmonary Arterial Hypertension: Collaboration With the Pharmaceutical Industry and Regulatory Agencies

2010 ◽  
Vol 9 (4) ◽  
pp. 214-219
Author(s):  
Robyn J. Barst
Keyword(s):  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
Drug Development ◽  
Phase 1 ◽  
Preclinical Studies ◽  
Phase 2 ◽  
Phase 3 ◽  
Preclinical Testing ◽  
New Drug ◽  
Pulmonary Arterial

Drug development is the entire process of introducing a new drug to the market. It involves drug discovery, screening, preclinical testing, an Investigational New Drug (IND) application in the US or a Clinical Trial Application (CTA) in the EU, phase 1–3 clinical trials, a New Drug Application (NDA), Food and Drug Administration (FDA) review and approval, and postapproval studies required for continuing safety evaluation. Preclinical testing assesses safety and biologic activity, phase 1 determines safety and dosage, phase 2 evaluates efficacy and side effects, and phase 3 confirms efficacy and monitors adverse effects in a larger number of patients. Postapproval studies provide additional postmarketing data. On average, it takes 15 years from preclinical studies to regulatory approval by the FDA: about 3.5–6.5 years for preclinical, 1–1.5 years for phase 1, 2 years for phase 2, 3–3.5 years for phase 3, and 1.5–2.5 years for filing the NDA and completing the FDA review process. Of approximately 5000 compounds evaluated in preclinical studies, about 5 compounds enter clinical trials, and 1 compound is approved (Tufts Center for the Study of Drug Development, 2011). Most drug development programs include approximately 35–40 phase 1 studies, 15 phase 2 studies, and 3–5 pivotal trials with more than 5000 patients enrolled. Thus, to produce safe and effective drugs in a regulated environment is a highly complex process. Against this backdrop, what is the best way to develop drugs for pulmonary arterial hypertension (PAH), an orphan disease often rapidly fatal within several years of diagnosis and in which spontaneous regression does not occur?

scholarly journals Bleeding by Bruton Tyrosine Kinase-Inhibitors: Dependency on Drug Type and Disease

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1103
Author(s):  
Philipp von Hundelshausen ◽  
Wolfgang Siess
Keyword(s):  
Clinical Trials ◽  
Tyrosine Kinase ◽  
B Cell ◽  
Kinase Inhibitors ◽  
Phase 1 ◽  
The Novel ◽  
B Cell Malignancies ◽  
Bruton Tyrosine Kinase ◽  
Dermatological Disorders ◽  
Reversible Covalent

Bruton tyrosine kinase (Btk) is expressed in B-lymphocytes, myeloid cells and platelets, and Btk-inhibitors (BTKi) are used to treat patients with B-cell malignancies, developed against autoimmune diseases, have been proposed as novel antithrombotic drugs, and been tested in patients with severe COVID-19. However, mild bleeding is frequent in patients with B-cell malignancies treated with the irreversible BTKi ibrutinib and the recently approved 2nd generation BTKi acalabrutinib, zanubrutinib and tirabrutinib, and also in volunteers receiving in a phase-1 study the novel irreversible BTKi BI-705564. In contrast, no bleeding has been reported in clinical trials of other BTKi. These include the brain-penetrant irreversible tolebrutinib and evobrutinib (against multiple sclerosis), the irreversible branebrutinib, the reversible BMS-986142 and fenebrutinib (targeting rheumatoid arthritis and lupus erythematodes), and the reversible covalent rilzabrutinib (against pemphigus and immune thrombocytopenia). Remibrutinib, a novel highly selective covalent BTKi, is currently in clinical studies of autoimmune dermatological disorders. This review describes twelve BTKi approved or in clinical trials. By focusing on their pharmacological properties, targeted disease, bleeding side effects and actions on platelets it attempts to clarify the mechanisms underlying bleeding. Specific platelet function tests in blood might help to estimate the probability of bleeding of newly developed BTKi.

ChemInform Abstract: Structure-Activity Relationships of 1,3-Benzoxazole-4-carbonitriles as Novel Antifungal Agents with Potent in vivo Efficacy.

ChemInform ◽  
2011 ◽  
Vol 42 (35) ◽  
pp. no-no
Author(s):  
Jun-ichi Kuroyanagi ◽  
Kazuo Kanai ◽  
Takao Horiuchi ◽  
Hiroshi Takeshita ◽  
Shozo Kobayashi ◽  
...  
Keyword(s):  
Antifungal Agents ◽  
In Vivo Efficacy ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Abstract Structure

scholarly journals Cerebral atrophy as outcome measure in short-term phase 2 clinical trials in multiple sclerosis

2010 ◽  
Vol 52 (10) ◽  
pp. 875-881 ◽  
Author(s):  
I. J. van den Elskamp ◽  
B. Boden ◽  
V. Dattola ◽  
D. L. Knol ◽  
M. Filippi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Outcome Measure ◽  
Cerebral Atrophy ◽  
Phase 2 ◽  
Short Term ◽  
Phase 2 Clinical Trials
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