DCAF1 is a substrate receptor of two distinct E3 ligases (CRL4 DCAF1 and EDVP), plays a critical physiological role in protein degradation, and is considered a drug target for various cancers. Antagonists of DCAF1 could be used toward the development of therapeutics for cancers and viral treatments. We used the WDR domain of DCAF1 to screen a 114-billioncompound DNA encoded library (DEL) and identified candidate compounds using similarity search and machine learning. This led to the discovery of a compound (Z1391232269) with an SPR K D of 11 μM. Structure-guided hit optimization led to the discovery of OICR-8268 (26e) with an SPR K D of 38 nM and cellular target engagement with EC 50 of 10 μM as measured by cellular thermal shift assay (CETSA). OICR-8268 is an excellent tool compound to enable the development of next-generation DCAF1 ligands toward cancer therapeutics, further investigation of DCAF1 functions in cells, and the development of DCAF1-based PROTACs.

Mass integration is a holistic approach to the optimal allocation, generation, and separation of streams and species. It addresses pollution using a combination of strategies including manipulation of process equipment, structural changes in the flowsheet, rerouting of streams and addition of new units. In the past, systematic mass integration techniques were developed to determine optimal strategies for the recycle and separation of process streams. The purpose of this paper is to introduce two novel contributions that can greatly expand the scope of mass integration for pollution prevention. First, maximum achievable pollution targets will be determined ahead of design and with little input data. In this context, we will illustrate the use of interval arithmetic to determine these targets. Second, pollution prevention through unit manipulation will be addressed. The devised interval-based targets posess the attractive feature that they are global regardless of the nonlinearity nature of the process model. These new concepts are illustrated with a case study. © 1999 Elsevier Science Ltd. All rights reserved.Keywords: Pollution; Mass integration; Interval; Targeting www.elsevier.com/locate/compchemeng root causes of the environmental problems at the heart of the process. In this regard, mass integration provides a unique framework for addressing in-plant pollution prevention. Mass integration is a holistic approach to the generation, separation, and routing of species and streams throughout the process. It is a systematic methodology that provides a fundamental understanding of the global flow of mass within the process and employs this understanding in identifying performance targets and optimising the allocation, separation, and generation of streams and species. For recent literature on mass integration, the reader is referred to the textbook by El-Halwagi (1997) and the review article by El-Halwagi and Spriggs (1998).The first step in conducting mass integration analysis is the development of a global mass allocation representation of the whole process from a species viewpoint as shown in Fig. 1. For each targeted species (e.g. each pollutant), there are sources (streams that carry the species) and process sinks (units that can accept the species). Process sinks include reactors, heaters/coolers, biotreatment facilities, and discharge media. Streams leaving the sinks become, in turn, sources. Therefore, sinks are also generators of the targeted species.

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