Despite the therapeutic success of monoclonal antibodies (mAbs), early identification of developable mAb-drug candidates with optimal manufacturability, stability, and delivery attributes remains elusive. Poor solution behavior, which manifests as high solution viscosity or opalescence, profoundly affects the developability of mAb-drugs. Employing a diverse dataset of 59 mAbs, including 43 approved products, and an array of molecular descriptors spanning colloidal, conformational, charge-based, hydrodynamic, and hydrophobic properties, we show that poor solution behavior is prevalent (>30%) in mAbs and is singularly predicted (>90%) by the diffusion interaction parameter (kD), a dilute-solution measure of colloidal self-interaction. No other descriptor, individually or in combination, was found to be as effective as kD. We also show that well-behaved mAbs, a significant subset of which bear high positive charge and pI, present no disadvantages with respect to pharmacokinetics in humans. Here, we provide a systematic framework with quantitative thresholds for selecting well-behaved therapeutic mAbs during drug-discovery.

No abstract

Commercial chemicals are used extensively across global urban centers, posing a potential exposure risk to 4.2 billion people, which accounts for 55% of the global population. Harmful chemicals are often assessed and regulated based on their environmental persistence, bioaccumulation, and toxic properties, under international and national initiatives such as the Stockholm Convention. However, current regulatory frameworks largely rely upon knowledge of the properties of the parent chemicals, with minimal consideration given to their atmospheric transformation products. This is mainly due to a signi cant lack of experimental data, as identifying transformation products in complex mixtures of airborne chemicals is an immense analytical challenge,hence making a comprehensive and reliable risk assessment for harmful chemicals currently unachievable. Here, we develop a novel framework, combining laboratory and eld experiments, non-target analysis techniques, and in-silico modelling, to identify and assess the hazards of airborne chemicals, which takes into account atmospheric chemical reactions. By applying this framework to organophosphate ame retardants, as representative chemicals of emerging concern, we nd that their transformation products are globally distributed across 18 megacities, representing a previously unrecognized exposure risk for the world's urban populations. Furthermore, the transformation products can be up to an order of magnitude more persistent, environmentally mobile, and toxic than the parent chemicals. The results indicate that the overall human and environmental risks associated with ame retardants could be signi cantly underestimated, while highlighting a strong need to include atmospheric transformations in the development of regulations for all harmful chemicals moving forward.

No abstract