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

Covalent Modifiers

AUGUST 4, 2024

4c00776 30 covalent drugs were used to assess clearance (CL) prediction reliability in animals and humans. CL predictions with allometric scaling were less robust compared to in vitro drug metabolism methods; the best results were obtained using the fu-corrected intercept model.

Pharmacokinetics 56

Pharmacokinetics Metabolic Stability Drugs 56

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

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 111

Pharmacokinetics Drugs 111

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

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

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

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 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

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

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

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

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

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.

FDA 105

FDA Drugs Pharmacokinetics Production 105

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

Chemical Biology and Drug Design

DECEMBER 5, 2024

A hybrid drug design approach was employed to develop novel leads ( 1K11K5 ). A hybrid drug design approach was employed by hybridization of pyrrolo[2,1- f ][1,2,4]triazine and 1-(methylpiperidin-4-yl)aniline pharmacophoric systems to develop novel leads ( 1K11K5 ). Studies were corroborated by in silico studies.

Immune Response 100

Immune Response Pharmacokinetics Regulations Treatment 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

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.

Animal Testing 106

Animal Testing Drugs Pharmacokinetics Regulations 106

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

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

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

Drug Patent Watch

DECEMBER 10, 2024

Generic drug development is a complex process that involves not only scientific and medical expertise but also adherence to strict legal and ethical standards. Scientific expertise plays a crucial role in ensuring that generic drugs are held to the same standards of quality, safety, and efficacy as their brand-name counterparts.

Drug Development 52

Drug Development Pharmacokinetics Compliance 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

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

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

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

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

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

Drug Target Review

OCTOBER 4, 2023

Antibody-drug conjugates (ADCs) have been a groundbreaking approach to cancer treatment with their ability to deliver cytotoxic drugs directly to diseased cells while sparing healthy tissues. 1 However, efforts proved less effective than the original drugs, owing mostly to insufficient toxicity against cancer cells.

Small Molecule 126

Small Molecule Drugs Immune Response Targeted Protein Degradation 126

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.

Pharmacokinetics 100

Pharmacokinetics Drugs Research 100

ASPET

JANUARY 31, 2024

First, we assessed the substrate potential of riboflavin towards other major drug transporters using established transfected cell systems. Overall, these data indicate that plasma riboflavin is a promising biomarker of BCRP that may offer a possibility to assess drug candidate as a BCRP modulator in early drug development.

Pharmacogenetics 100

Pharmacogenetics Pharmacokinetics Drug Development Drugs 100

ASPET

JANUARY 22, 2024

Profiling NT-0796 in mice humanized with respect to CES-1 biology enables critical modeling of the pharmacokinetics and pharmacodynamics of this novel therapeutic candidate. Significance Statement Inhibition of NLRP3 represents a desirable therapeutic strategy for the treatment of multiple human disorders.

Pharmacokinetics 100

Pharmacokinetics DNA Engineering International 100

PPD

SEPTEMBER 19, 2023

During the drug development process, companies have a choice of different approaches based on their development plan requirements. Others conduct multiple, simpler studies, sometimes in parallel and sometimes staggered, often reflecting the level of risk and complexity the sponsor is willing to incorporate into their drug program.

Clinical Trials 98

Clinical Trials Pharmacokinetics Drug Development Clinical Development 98

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

Practical Cheminformatics

JANUARY 8, 2024

Picking up where we left off in Part I , this post covers several other ML in drug discovery topics that interested me in 2023. Most of the LLM activity in the drug discovery space in 2023 was reported as preprints from academic groups. Most of the drug discovery examples were underwhelming. Here’s the structure of Part II.

Drugs 141

Drugs Small Molecule Bioinformatics Packaging 141

ASPET

APRIL 26, 2024

This lack of activity could be due to insufficient CNS exposure to the unbound drug. In this study, we investigated the systemic pharmacokinetics and subsequent CNS distribution of two potent HDACIs, vorinostat and quisinostat, in the murine model.

Pharmacogenetics 100

Pharmacogenetics Pharmacokinetics Clinical Trials Trials 100

ASPET

AUGUST 10, 2023

Pharmacokinetic half-lives ranged from 55 to 100 hours over the clinically relevant dose range, consistent with the expected half-life extension by glycoPEGylation. These findings provide evidence that pegozafermin is a promising candidate molecule for the treatment of patients with NASH or SHTG.

Cell Based Assays 100

Cell Based Assays Pharmacokinetics Regulations Treatment 100