Resources
Peptide-drug conjugates: A new paradigm for targeted cancer therapy
Multiplexed mapping interactome of GPCRs with receptor activity–modifying proteins
Protein-protein interactions regulate signal transduction by heterotrimeric guanine nucleotide–binding regulatory proteins (G proteins). G protein–coupled receptors (GPCRs), which comprise a superfamily of approximately 720 distinct receptors, activate G proteins in response to ligand binding. They screened for interactions in three cell lines and found 23 endogenously expressed GPCRs that formed complexes with RAMPs
Proximity-Based Ubiquitin Ligase Substrate
Over 600 E3 ligases in humans execute ubiquitination of specific target proteins in a spatiotemporal manner to elicit desired signalling effects. Here, they have developed a ubiquitin-specific proximity-based labeling method to selectively biotinylate substrates of a given ubiquitin ligase. They anticipate that our method could be widely adapted to all classes of ubiquitin ligases to identify substrates.
Extensible Surrogate Potential Optimized
This approach is not only sufficiently expressive to reproduce legacy atom types, but that it can learn and extend existing molecular mechanics force fields, construct entirely new force fields applicable to both biopolymers and small molecules from quantum chemical calculations, and even learn to accurately predict free energies from experimental observables.
The Next Leap in Pet Health: Longevity Drugs
Dog owners know the pain of a pet's short life. Scientists are developing drugs to extend dogs' lives, potentially reducing this sorrow. Loyal, a biotech startup in San Francisco, is leading the effort with three drugs under FDA review. This article examines these drugs and their approval timelines.
Factors Contributing to Unsuccessful Clinical Trials
As the process advances from pre-clinical stages to phase 3, investments in resources, time, and finances escalate. Hence, the expense of a failed phase 3 trial extends beyond its singular cost, encompassing all preceding trials and the value of time invested in exploring alternate potential solutions.
Scaling Laws for Autoregressive Generative Modeling
Design of structurally diverse intrinsically disordered protein variants
Intrinsically disordered proteins (IDPs) perform a broad range of functions in biology, suggesting that the ability to design IDPs could help expand the repertoire of proteins with novel functions. Computational design of IDPs with specific conformational properties has, however, been difficult because of their substantial dynamics and structural complexity.
Contextual AI Models for Single-Cell Protein Biology
Understanding protein function and developing molecular therapies require deciphering the cell types in which proteins act as well as the interactions between proteins. However, modeling protein interactions across biological contexts remains challenging for existing algorithms. Here they introduce PINNACLE, a geometric deep learning approach that generates context-aware protein representations.
SRF Transcriptionally Regulates During CNS Myelination
Together with a recent discovery that SRF promotes oligodendrocyte rejuvenation, the findings uncover a pathway promoting myelin formation that may represent a therapeutic target for restoring myelin in the aged or diseased CNS. Myelin is essential for the development and function of the central nervous system (CNS), and its loss or dysfunction is central to aging and neurodegenerative diseases.
Venture Funding, Deal Making Slowed in 2023
Venture capital firms are increasingly investing in later-stage drug companies, which accounted for about 40% of deals in 2023. Rather than invest heavily in preclinical work, VCs now appear to be waiting for drug developers to enter or have a road map to clinical trials
Will 2024 mean spring for the biotech sector?
After a chilly 2022, so far 2023 is emerging as a slow thaw for the sector, as higher risk and less-proven companies get swept away and investors are beginning to emerge again for those biotechs that have solid fundamentals, a strong management team and good science.
A molecularly engineered, broad-spectrum anti-coronavirus lectin inhibits SARS-CoV-2
Cyclic Extension Amplifies Signals for High-Sensitivity Single-Cell Mass Cytometry
Mass cytometry's sensitivity is enhanced by Amplification by Cyclic Extension (ACE), a technology that amplifies signals on >30 protein epitopes, enabling detailed protein quantification and multiparametric tissue imaging in various biological processes. ACE's utility is demonstrated in low-abundance protein quantification and dynamic signalling analysis in human cells.
Laboratory Animals and Non-Animal Alternatives
The number of mice bred and the total number of animal experiments began a new downward trend in 2015. The production of genetically modified organism (GMO) mice caused an upward trend in the total number of laboratory animal “procedures” from around 1995 to 2015. However, the actual USE of animals in “experiments” remained relatively flat and has been trending down since 2015.
Computational Approaches in Preclinical Studies
Because undesirable pharmacokinetics and toxicity are significant reasons for the failure of drug development in the costly late stage, it has been widely recognized that drug ADMET properties should be considered as early as possible to reduce failure rates in the clinical phase of drug discovery.
What happens to biotech now that venture capital is out of reach?
After all, the COVID-19 pandemic had shined a positive spotlight on the biopharmaceutical industry, and initial public offerings (IPOs) were booming.
But the last two years have seen venture capital and overall funding within the industry dry up due to the economic downturn, which has heavily impacted many biotech companies.
Tardigrade Hypsibius exemplaris dramatically upregulates DNA repair pathway genes
Expanding the Molecular Language of Protein Liquid–Liquid Phase Separation
Understanding the relationship between a polypeptide sequence and its phase separation has important implications for analysing cellular function, treating disease and designing novel biomaterials. Several sequence features have been identified as drivers for protein liquid–liquid phase separation (LLPS), schematized as a ‘molecular grammar’ for LLPS.
Charles River Looks to Alternative Solutions
Understanding that advancement requires collaboration, AMAP involves the continuation of Charles River’s strategy to partner with companies to co-develop solutions and continuing to identify externally-developed technologies to enhance client offerings. They have launched Alternative Methods Advancement Project (AMAP), an initiative dedicated to developing alternatives to reduce animal testing
Predictive Solubility Prediction & Interpretation
The water solubility of molecules, crucial in chemical and medical research, has led to the exploration of machine learning methods for predicting molecular properties. Despite advancements in predictive accuracy, existing methods lacked interpretability. To address this, we propose a novel multi-order graph attention network (MoGAT) that enhances both prediction accuracy and result interpretation.
FDA Drops Mandatary Animal Trial Legislation
A new U.S. law has eliminated the requirement that drugs in development must undergo testing in animals before being given to participants in human trials.
Animal rights advocates have long pushed for such a move, and some in the pharmaceutical industry have argued that animal testing can be ineffective and expensive.
Exploring the intersection of biotech and VC
Biotech is one of the most unique, interesting, and high-risk corners in venture capital. Across the VC landscape, there are very few sectors in which companies are striving to save lives, and even fewer that can provide the same level of outsized returns.