Molecular Design

MARCH 31, 2019

Drug design is a multi-objective endeavor. Other objectives such as controllability of exposure are much less easily defined and this means that drug design is indirect. Some objectives such as maximization of affinity against target(s) and minimization of affinity against anti-targets are easily defined.

Pharmacokinetics 52

Pharmacokinetics Treatment Drugs 52

ASPET

SEPTEMBER 7, 2023

Awareness of drug interactions involving opioids is critical for patient treatment as they are common therapeutics used in numerous care settings including both chronic and disease related pain. Not only do opioids have narrow therapeutic indexes and are extensively used, but they have the potential to cause severe toxicity.

Pharmacokinetics 100

Pharmacokinetics Drugs Treatment Disease 100

Broad Institute

JULY 17, 2024

Still, more than 90 percent of drug candidates fail in clinical trials, with even more that never make it to the clinical stage. Many drugs fail because they simply aren’t safe. Seal began this work after wondering if more toxicology insights could be gleaned from a drug candidate’s chemical structure.

Pharmacokinetics 84

Pharmacokinetics Molecular Biology Drugs FDA 84

ASPET

SEPTEMBER 16, 2024

PF-06952229 (MDV6058) selected using rational drug design is a potent and selective TGFβRI inhibitor (TGFβRIi) with a relatively clean off-target selectivity profile and good pharmacokinetic properties across species.

Pharmacokinetics 100

Pharmacokinetics Packaging Drugs 100

ASPET

AUGUST 8, 2024

Lenacapavir (LEN), a long-acting injectable, is the first approved human immunodeficiency virus type 1 capsid inhibitor and one of a few FDA-approved drugs that exhibit atropisomerism. The volume of distribution was moderate in nonclinical species and consistent with the tissue distribution observed by whole body autoradiography in rats.

Pharmacogenetics 100

Pharmacogenetics Pharmacokinetics FDA Approval Virus 100

Alta Sciences

JUNE 24, 2023

Design and Validation of a Bioanalytical Method to Support a Clinical Pharmacokinetic Study Involving the Use of Multiple Lots of the Biological Therapeutic Drug lperez Sat, 06/24/2023 - 08:07 Publication Altasciences_WRIB_2023_Design_and_Validation_of_a_Bioanalytical_Method_to_Support_a_Clinical_Pharmacokinetic_Study.pdf Tags Bioanalysis Date of publication (..)

Pharmacokinetics 40

Pharmacokinetics Drugs 40

ASPET

AUGUST 5, 2024

Proinflammatory cytokines, elevated during inflammation caused by infection and/or autoimmune disorders, result in reduced clearance of drugs eliminated primarily by cytochrome P450 enzymes (CYPs). However, the effect of cytokines on hepatic drug transporter expression or activity has not been well-studied. or 1 ng/mL).

Pharmacogenetics 100

Pharmacogenetics Pharmacokinetics Drugs 100

ASPET

SEPTEMBER 16, 2024

GBM has a poor prognosis despite aggressive treatment, in part due to lack of adequate drug permeability at the BBB. CNS distribution of elimusertib is partially limited by P-gp efflux at the BBB, and high binding to CNS tissues leads to low levels of pharmacologically active (unbound) drug in the brain.

Pharmacogenetics 100

Pharmacogenetics DNA Pharmacokinetics Treatment 100

ASPET

AUGUST 21, 2024

ICH established S7B and E14 guidelines in 2005 to prevent drug-induced torsade de pointes (TdP), effectively preventing the development of high-risk drugs. However, those guidelines unfortunately hampered the development of some potentially valuable drug candidates despite not being proven to be proarrhythmic.

Compliance 100

Compliance Pharmacokinetics Drugs Engineering 100

SCIENMAG: Medicine & Health

NOVEMBER 1, 2023

A small clinical trial with a pharmacokinetic sub-study, led by a world-renowned pharmacologist at the University of Houston, has demonstrated the promising effectiveness of the drug Riluzole for improving functionality in people with acute spinal cord injuries (SCI) if the drug is taken within 12 hours post-injury.

Clinical Trials 86

Clinical Trials Trials Pharmacokinetics Drugs 86

Broad Institute

OCTOBER 29, 2024

New drug triggers rapid cell death in cancer models By Karen Zusi-Tran October 29, 2024 Breadcrumb Home New drug triggers rapid cell death in cancer models BRD-810 inhibits the MCL1 protein and reactivates apoptosis in tumor cells, displaying therapeutic potential in animal models. The result was the compound named BRD-810.

Drugs 133

Drugs Small Molecule Pharmacokinetics Clinical Trials 133

ASPET

JUNE 27, 2024

Furthermore, we evaluated the in vivo pharmacokinetics of the analogs following single dose IV and oral administration. Surprisingly, and at odds with their pharmacokinetic and in vitro human activity data, most analogs potently induced uterotrophic effects in estrogen-naïve female mice.

Pharmacokinetics 100

Pharmacokinetics Drug Development Disease Drugs 100

Covalent Modifiers

NOVEMBER 1, 2024

Through Zn2+-dependent hydrolysis of acyl-lysine modifications, histone deacetylases (HDACs) are key regulators of disease-implicated signaling pathways and tractable drug targets in the clinic. Raouf and Carlos Moreno-Yruela JACS Au , 2024 DOI: 10.1021/jacsau.4c00828

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Pharmacokinetics Regulations Disease Drugs 64

DrugBank

SEPTEMBER 19, 2024

Oral drug delivery remains the gold standard in pharmaceutical administration. Compared to other routes, like injectables, oral drugs are cost-effective to manufacture and administer. However, translating a promising therapeutic candidate into a successful oral medication presents pharmacokinetic and pharmacodynamic challenges.

Pharmacokinetics 82

Pharmacokinetics Drugs Treatment Disease 82

Drug Patent Watch

OCTOBER 30, 2023

Over the past two decades, Bayer Pharma has developed an in silico absorption, distribution, metabolism, and excretion (ADMET) platform with the aim of generating models for various pharmacokinetic and physicochemical… The post Advancements in In Silico ADMET Modeling: A 20-Year Journey of Machine Learning in Drug Discovery at Bayer Pharma appeared (..)

Pharmacokinetics 106

Pharmacokinetics Drugs 106

ASPET

SEPTEMBER 28, 2023

These protocols were then used to determine the plasma pharmacokinetics of agmatine and the extent of distribution to the CNS. Precision and accuracy of the protocol met Food and Drug Administration (FDA) standards in surrogate matrix, as well as in corrected concentrations in appropriate matrices.

Pharmacokinetics 100

Pharmacokinetics FDA Therapies Drugs 100

Covalent Modifiers

NOVEMBER 22, 2024

4c01541 Covalent drugs provide pharmacodynamic and pharmacokinetic advantages over reversible agents. Among other nucleophilic residues that could be in principle used for the design of covalent drugs, histidine (His) has not been given proper attention despite being in principle an attractive residue to pursue but underexplored.

Pharmacokinetics 59

Pharmacokinetics Drugs 59

ASPET

OCTOBER 24, 2023

The pharmacokinetic and pharmacodynamic properties of orally administered BBP-671 evaluated in cannulated rats showed that CoA concentrations were elevated in blood, liver and brain. Significance Statement The blood brain barrier represents a major hurdle for drugs targeting brain metabolism.

Metabolic Stability 100

Metabolic Stability Pharmacokinetics Regulations Treatment 100

ASPET

OCTOBER 23, 2024

Neither nimodipine nor NP10679 alter each other's pharmacokinetic profile, suggesting no obvious drug-drug interactions. In addition, we observed an unexpected reduction in SAH-induced luminal narrowing of the middle cerebral artery.

Clinical Development 100

Clinical Development Treatment Pharmacokinetics Drugs 100

Common Sense for Drug Policy Blog

OCTOBER 29, 2024

The only studies reported in the FDA package inserts for both products are pharmacokinetic studies in healthy volunteers, which demonstrated substantially higher naloxone plasma levels than standard doses of naloxone (0.4 Int J Drug Policy. mg IM vs. 8 mg IN and 2 mg IM vs. 5 mg IM, respectively). In 2023, the FDA approved a 2.7

Pharmacokinetics 52

Pharmacokinetics FDA Approval Packaging FDA 52

FDA Law Blog: Biosimilars

JULY 23, 2024

Lenz, Principal Medical Device Regulation Expert — For several years, FDA has requested that sponsors of drug or biologic led combination products identify essential performance requirements (EPRs) related to the device constituent in their applications. By Adrienne R. does not use this term.

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FDA Drugs Pharmacokinetics Production 104

Chemical Biology and Drug Design

AUGUST 18, 2024

ABSTRACT To increase the success rate of drug discovery, one practical strategy is to begin molecular hybridisation. Benzimidazole and oxadiazole are privileged structures in medicinal chemistry and are widely used in drug discovery and development due to their vast biological properties.

Pharmacokinetics 100

Pharmacokinetics Drugs Research 100

DrugBank

OCTOBER 17, 2024

Data science has emerged as an innovative tool in the biopharmaceutical industry, leveraging the power of machine learning and artificial intelligence to drive innovation and efficiency across the entire drug development lifecycle.

Drug Development 71

Drug Development Metabolic Stability Clinical Trials Drugs 71

Alta Sciences

SEPTEMBER 27, 2024

Featuring two scenarios that explore the complexities of bioanalysis for immunomodulators, The Altascientist offers practical considerations for ensuring accurate bioanalysis, as well as pharmacokinetic, pharmacodynamic , and safety data in clinical trials. Each class of immunomodulator has a defined complexity and mechanism of action.

Clinical Trials 52

Clinical Trials Trials Pharmacokinetics Small Molecule 52

Drug Target Review

APRIL 22, 2024

What are the primary methods used for bioconjugation in antibody drug-conjugate (ADC) development, and how do they influence the stability and efficacy of the resulting ADCs? Despite excellent pharmacokinetic and stable antibody-linker connections, such ADCs have yet to receive market approval.

Pharmacokinetics 75

Pharmacokinetics Organic Chemistry Drugs Engineering 75

Metabolite Tales Blog

NOVEMBER 13, 2024

Our paper pick this month and latest blog describes the routes of biotransformation of Cytokinetics’ aficamten, a drug mainly eliminated by metabolism [1,2]. It’s hypothesized that any parent drug might also be degraded in the intestine to M18. Drug Metabolism and Disposition April 1, 2020, 48 (4) 317-325; DOI: [link]. [5]

Pharmacokinetics 52

Pharmacokinetics Small Molecule Production Clinical Development 52

ASPET

JUNE 27, 2024

The primary endpoint was the peak effect (Emax) on a bipolar Drug Liking visual analog scale (VAS). Secondary VAS and pharmacokinetic (PK) endpoints and adverse events were assessed. Compared to placebo, a 20mg dose of lenabasum did not increase ratings of Drug Liking and had no distinguishable effect on other VAS endpoints.

Pharmacokinetics 100

Pharmacokinetics FDA Approval FDA Disease 100

The Premier Consulting Blog

JULY 31, 2024

In this blog, we explain the role of clinical pharmacology in drug development and demonstrate how the right strategy can accelerate development under the US Food and Drug Administration (FDA) 505(b)(1) and 505(b)(2) New Drug Application (NDA) pathways.

Clinical Pharmacology 52

Clinical Pharmacology Drug Development Pharmacokinetics Drugs 52

Chemical Biology and Drug Design

MARCH 7, 2024

The physicochemical, pharmacokinetic, drug-like, and drug-score features of all synthesized compounds were assessed using the online Swiss ADME and Protein Plus software. All of them met Lipinski's rule of five and had drug-likeness and drug score values of 0.55 AutoDock 4.2 kJ/mol, respectively.

Pharmacokinetics 100

Pharmacokinetics Drugs Research 100

ASPET

JANUARY 22, 2024

Currently, drugs targeting NF-B inhibition have not yet been applied in clinical practice. The pharmacokinetics was measured by LC-MS/MS analysis. Nuclear factor-B (NF-B) plays a central role in inflammatory responses, while its physiological functions are essential for cell survival and proliferation.

Immune Response 100

Immune Response Pharmacokinetics Production Drugs 100

ASPET

MAY 4, 2023

Drug biliary clearance (CL bile ) in vivo is among the most difficult pharmacokinetic parameters to predict accurately and quantitatively because biliary excretion is influenced by metabolic enzymes, transporters, and passive diffusion across hepatocyte membranes.

Pharmacokinetics 100

Pharmacokinetics Drugs 100

Drug Target Review

JUNE 5, 2023

Can you tell us more about ZW191 and its potential as an FRα-targeting antibody-drug conjugate? ZW191 is comprised of a novel fully humanised IgG1 antibody covalently conjugated to a novel topoisomerase 1 inhibitor ZD06519, a camptothecin derivative, via endogenous interchain cysteines with a drug-to-antibody ratio (DAR) of eight.

Treatment 100

Treatment Pharmacokinetics Drugs Cell Biology 100

Chemical Biology and Drug Design

JANUARY 29, 2024

In silico ADME prediction of these compounds revealed the good drug-likeness nature and followed Lipinski's rule of five. In-silico ADME studies significant values of pharmacokinetic parameters and demonstrated good drug like characteristics based on Lipinski's rule of five.

Pharmacokinetics 100

Pharmacokinetics Production Drugs Research 100

The Premier Consulting Blog

MAY 31, 2023

As a cornerstone of the drug development process, nonclinical investigational new drug (IND)-enabling studies are essential for supporting first-in-human (FIH) dosing for novel therapeutics. Pharmacology A typical IND-enabling package includes information on the primary, secondary, and safety pharmacology of the drug.

Packaging 52

Packaging Pharmacokinetics Small Molecule Clinical Trials 52

biobide

SEPTEMBER 29, 2023

Within the field of Drug Discovery and Development the term “ New Alternative Methodologies ” (NAMs) refers to the use of new and innovative testing methods that come to replace traditional animal models. The use of in silico models allows the fastening of the first steps of Drug Discovery, representing an immense advance in the field.

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Alta Sciences

AUGUST 12, 2024

Metabolic Drug Development: A to Z Solutions blussier Mon, 08/12/2024 - 18:07 HTML In the complex and dynamic field of metabolic drug development, partnering with an accomplished contract research organization is essential. We support data management both at our clinics and at external sites.

Drug Development 40

Drug Development Clinical Trials Pharmacokinetics Drugs 40

Chemical Biology and Drug Design

MARCH 5, 2024

The outcomes of the tested compounds 5d , 5e , and 5f have shown more potent activity when compared to the standard drug erlotinib. The potent compounds 5d , 5e , and 5f were subjected to in silico pharmacokinetic assessment by SWISS, ADME, and pkCSM.

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