Curate this paper into an ORD dataset

Build an Open Reaction Database (ORD) dataset of the reactions reported in:

• Paper: Integrated Direct-to-Biology Platform for the Nanoscale Synthesis and Biological Evaluation of PROTACs
• Authors: Rebecca Stevens, Enrique Bendito-Moll, David J. Battersby et al.
• Published: J. Med. Chem., 2023-11-07
• DOI: 10.1021/acs.jmedchem.3c01604
• ORD wishlist card: open on GitHub

The reference input card holds these facts, the source-data locations and the notes below in machine-readable form.

Scope

Every reaction the paper reports with its data (the wishlist estimates about 650 reactions; HTE): inputs with amounts and roles, conditions, workups, outcomes and provenance, following the ord-curation Skill. Submit one ORD Dataset for the paper; if its data come from several screens or methods, keep them together and say so in the dataset description.

Source data

Source: Stevens et al., J. Med. Chem. 2023 (doi:10.1021/acs.jmedchem.3c01604); ChemRxiv preprint doi:10.26434/chemrxiv-2023-1b47d. Ultra-HTE direct-to-biology PROTAC synthesis: ~650 amide couplings between POI-binding amines and an E3 ligase-linker acid library in a 1536-well plate. LCMS outcomes were processed with PyParse, and an 87% success rate is reported. Public data: the SI PDF (methods, intermediates) and a small SI CSV with SMILES and degradation data (pDC50/Dmax) for 22 compounds. The paper gives intermediate structures but not the final product structures of the library. The E3 ligase-linker acid library is referred to only by name/ID, so a full per-well reaction dataset needs structures and outcomes that are not in the public record. Earlier HER2 D2B validation plates are also described.

Known locations:

• https://api.figshare.com/v2/articles/24517047: ACS SI file jm3c01604_si_002.csv (3440 bytes): 22 compounds with SMILES, purified and D2B pDC50/Dmax. Biological data for hits, not the full reaction plate. (license: Labeled CC BY-NC 4.0 on figshare (ACS SI mirror); not verified against ACS terms)
• https://api.figshare.com/v2/articles/24517044: ACS SI PDF jm3c01604_si_001.pdf (1.2 MB): methods, general procedures, characterisation (license: Labeled CC BY-NC 4.0 on figshare (ACS SI mirror))
• https://doi.org/10.26434/chemrxiv-2023-1b47d-v2: ChemRxiv preprint (v2) with its own ~1 MB Supporting Information PDF (license: unknown (ChemRxiv API was blocked; license not verified))
• https://doi.org/10.1021/acs.jmedchem.3c01604: J. Med. Chem. 2023 article (closed access) (license: ACS standard (closed))

Pitfalls

Nanoscale 1536-well plate. Outcomes are LCMS-derived purity/conversion (pass/fail thresholds for progressing to assay), not isolated yields. Crude mixtures went straight to biology, so products are not isolated or characterized. Several plate experiments (HER2 validation, BRD4 campaign) could be split into separate datasets. Biological endpoints (pDC50/Dmax) are outside ORD reaction outcomes.

Deliver

• dataset: the ORD Dataset, compressed (.binpb.gz, .pb.gz, .txtpb.gz, .pbtxt.gz or .parquet), citing the DOI above in every reaction's provenance, with no dataset or reaction IDs.
• sources: a .zip with a README.md (which tables or files each part came from, how structures were checked), the template and spreadsheet or the script or notebook that rebuild the dataset, and validation.txt, the output of ORD's validator (ord-schema 0.8.3) on the dataset file.

Before you start

Open the wishlist card. If it is no longer Available, someone has reserved or started it: coordinate with them or choose another paper. Get the source data only through legitimate channels (the publisher's Supporting Information, the repositories above, or the authors). Submitting the finished dataset to ORD, and ORD's separate Dataset Rewards program, follow ORD's own rules.