In 2021, the FDA approved asciminib (ABL001), an allosteric inhibitor of the Philadelphia tyrosine kinase, which plays a key role in leukemia development. The drug features a chlorodifluoromethoxy- (ClF2CO-) moiety, which embeds deeply within the myristate pocket. This group replaces the more commonly used CF3O- moiety, doubling the binding affinity by forming a Cl∙∙∙O=C halogen bond with the backbone of Leu448. Interestingly, the transition from CF3O- to ClF2CO- did not increase lipophilicity. This example underscores the potential of mixed halogenated moieties for fine-tuning pocket interactions and optimizing drug pharmacology.
Case study
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We offer
Over 50 mixed haloalkoxy compounds from stock on 5-10 gram scale
A gateway to a world of boundless possibilities in molecular evolution
Enamine proudly introduces the Late-Stage Functionalization Kit (LSF Kit) — a unique collection of Building Blocks equipped with specially engineered functional “handles” designed for precise and efficient late-stage transformations. This kit unlocks a new level of creative freedom for medicinal chemistry teams, enabling them to explore structure–activity relationships (SAR) and generate new analogs without altering the core molecular scaffold — faster, smarter, and more efficiently.
Key Features of the Late-Stage Functionalization Kit
- Building Blocks equipped with functional “handles” compatible with modern LSF methodologies.
- Includes activated NHPI esters — ideal substrates for mild decarboxylative C(sp³)-radical generation.
- Bonus components: two ligands and a catalyst for an immediate start to diversification workflows.
- Orthogonal compatibility with aryl and heteroaryl halides, BPin fragments, alkynes, azides, sulfonamides, nitriles, CF₃ groups, and more.
- Medicinal-chemistry-focused motifs: azetidines, pyrrolidines, piperidines, morpholines, and other high-value heterocycles.
Each building block in Enamine LSF Kit is equipped with a synthetically privileged functional group-carefully optimized for flawless transformations, including cross-coupling, C‑H activation, click chemistry, as well as photoredox and radical processes. Thanks to this, the Late-Stage Functionalization Kit integrates seamlessly into modern ligand- and medicinal-design strategies, providing researchers with unprecedented flexibility and speed.
Advantages of the Late-Stage Functionalization Kit
- Rapid SAR expansion: enables the creation of analogs without altering the core molecular architecture
- Minimal synthetic “repair”: replace parts, not the scaffold
- Support for cutting-edge chemistry: radical, photoredox, and electrochemical approaches
- Reliable supplier: Enamine offers one of the world’s largest collections of building blocks (>1.5 million compounds) with scalable logistics (enamine.net)
- Easy access: order via the Enamine catalog and online store
Examples of Enamine LSF Kit components and bonus additions — two ligands and a catalyst
Enamine LSF Kit will be an ideal solution for medicinal chemistry teams working on lead optimization and aiming to rapidly introduce saturated fragments or vary substituents without unnecessary synthetic redesign. It will also benefit researchers seeking to minimize molecular scaffold re-engineering and accelerate the progression from hit to lead. In addition, the kit is especially valuable for laboratories looking for a ready-to-use “plug-and-play” solution for late-stage transformations that is compatible with the most advanced methodologies.
Our specialists are continuously expanding and diversifying this collection of Late-Stage Functionalization Kit by introducing new classes of different compounds, thereby supporting and accelerating drug discovery workflows.
Availability
Enamine LSF Kit is available for order through the Enamine catalog and online shop. Full specifications, a list of included compounds, application examples, and instructions can be found on the Enamine website or obtained through local representatives. (For details and delivery terms, please contact the EnamineStore.com or our sales department.)
Selected publication on the use of Late-Stage Functionalization Kit
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Control of Redox-Active Ester Reactivity Enables a General Cross-Electrophile Approach to Access Arylated Strained Rings.
Daniel C. Salgueiro, Benjamin K. Chi, Ilia A. Guzei, Dr. Pablo García-Reynaga, Prof. Daniel J. Weix Angewandte Chemie 2022, 134 (33), e202205673. DOI: 10.1002/ange.202205673
Developed to expand the structural diversity of Molecular Glues
880 compounds
The Phenyl Dihydrouracil (PD) scaffold introduces a fundamentally new concept in the field of CRBN binders. Departing from the paradigm of the glutarimide ring, this scaffold offers significant advantages. In particular, the dihydrouracil fragment demonstrates much higher chemical stability, including resistance to hydrolysis, which has been critical for various Molecular Glues.
The absence of a chiral center solves another major issue for Molecular Glues containing amino glutarimide fragments — the problem of racemization. Moreover, Phenyl Dihydrouracil (PD) scaffold-based Molecular Glues and PROTACs show improved protein degradation efficacy and cellular potency.
Representative examples of building blocks for library design
Examples of the molecules in the library
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Typical Formats
Catalog No.
PD-880-0-Z-20
Compounds
880
1 plate
Amount
≤ 300 nL of 20 mM of DMSO solutions
Plates and formats
1536-well Echo LDV microplates, first and last four columns empty, 1280 compounds per plate
Price
Catalog No.
PD-880-10-Y-20
Compounds
880
3 plates
Amount
10 µL of 20 mM DMSO solutions
Plates and formats
384-well Echo plates, Labcyte #LP-0200, 320 compounds per plate, first two and last two columns empty
Price
Catalog No.
PD-880-50-X-20
Compounds
880
11 plates
Amount
50 µL of 20 mM DMSO solutions
Plates and formats
96-well plates, 80 compounds per plate, first and last columns empty; Greiner #781270
Price
*We will be happy to provide our library in any other most convenient for your project format. Please select among the following our standard microplates: Greiner Bio-One 781270, 784201, 781280, 651201 or Echo Qualified 001-12782 (LP-0200), 001-14555 (PP-0200), 001-6969 (LP-0400), C52621 or send your preferred labware. Compounds pooling can be provided upon request.
Selected publication
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Phenyl Dihydrouracil: An Alternative Cereblon Binder for PROTAC Design.
ACS Med. Chem. Lett. 2023, 14, 2, 141–145. DOI: 10.1021/acsmedchemlett.2c00436
Support
We offer comprehensive support in developing your hit compounds. Naturally such programs are realised most efficiently when biological actives originate from our screening collection. However, even if the hit compounds are from the collections of other vendors lead identification and optimization projects can proceed most productively in our hands. Sometimes for this we only need to synthesize first examples of the given chemical series and validate synthesis route.
Developed to expand the structural diversity of Molecular Glues
640 compounds
The Phenyl Amino Glutarimide (PAG) scaffold is an alternative binder to the CRBN E3 ligase. This type of binder retains the same binding capability to the protein and a similar physicochemical profile, while offering a 16% reduction in molecular weight. This makes the PAG scaffold an attractive alternative candidate for the design of various Molecular Glues.
Our library is 80% designed around published and validated Phenyl Amino Glutarimide (PAG) CRBN E3 binders with high variability in exit vectors. The remaining 20% of the library is built around various heteroaromatic amino glutarimides.
Representative examples of building blocks for library design
Examples of the molecules in the library
Typical Formats
Catalog No.
PAG-640-0-Z-20
Compounds
640
1 plate
Amount
≤ 300 nL of 20 mM of DMSO solutions
Plates and formats
1536-well Echo LDV microplates, first and last four columns empty, 1280 compounds per plate
Price
Catalog No.
PAG-640-10-Y-20
Compounds
640
2 plates
Amount
10 µL of 20 mM DMSO solutions
Plates and formats
384-well Echo plates, Labcyte #LP-0200, 320 compounds per plate, first two and last two columns empty
Price
Catalog No.
PAG-640-50-X-20
Compounds
640
8 plates
Amount
50 µL of 20 mM DMSO solutions
Plates and formats
96-well plates, 80 compounds per plate, first and last columns empty; Greiner #781270
Price
*We will be happy to provide our library in any other most convenient for your project format. Please select among the following our standard microplates: Greiner Bio-One 781270, 784201, 781280, 651201 or Echo Qualified 001-12782 (LP-0200), 001-14555 (PP-0200), 001-6969 (LP-0400), C52621 or send your preferred labware. Compounds pooling can be provided upon request.
Selected publication
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Design and Synthesis of Novel Cereblon Binders for Use in Targeted Protein Degradation
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J. Med. Chem. 2023, 66, 23, 16388–16409. DOI: 10.1021/acs.jmedchem.3c01848 -
Evaluation of Cereblon-Directing Warheads for the Development of Orally Bioavailable PROTACs.
J. Med. Chem. 2025, 68, 3, 3591–3611. DOI: 10.1021/acs.jmedchem.4c02709
Support
We offer comprehensive support in developing your hit compounds. Naturally such programs are realised most efficiently when biological actives originate from our screening collection. However, even if the hit compounds are from the collections of other vendors lead identification and optimization projects can proceed most productively in our hands. Sometimes for this we only need to synthesize first examples of the given chemical series and validate synthesis route.