PROTAC Structure Modification Service

PROTACs possess the potential to specifically induce the degradation of target proteins, enabling the targeting of "undruggable" proteins that traditional drug design often struggles to effectively modulate. Leveraging its powerful computational platform, CD ComputaBio provides structural modification services for PROTACs, assisting researchers by optimizing PROTAC molecule structures through computational simulation and analysis.

Introduction to PROTACs

PROTACs (Proteolysis-targeting Chimeras) represent an innovative therapeutic modality. They are designed as heterobifunctional small molecules, where one end binds to a target protein and the other end recruits an E3 ubiquitin ligase, connected by a linker. This "ternary" complex formation brings the E3 ligase into proximity with the target protein, leveraging the cell's own ubiquitin-proteasome system to specifically degrade the target. Compared to traditional inhibitors, PROTACs do not require high concentrations for inhibition, hold promise for overcoming drug resistance, and can target "undruggable" targets and intracellular proteins, offering new hope for the treatment of diseases like cancer.

Fig 1. Proteolysis-targeting chimeras in the clinic for cancer indications. (Vetma V, et al., 2024)

PROTAC Structure Modification

Structural modification of PROTACs is crucial for ensuring their efficacy, selectivity, and drug-like properties. Structural factors can influence the stability of PROTAC molecules, their ability to effectively trigger protein degradation, and their interactions with the target and E3 ligase. By adjusting the structures of the targeting ligand, the E3 ligase ligand, and the linker, it is possible to enhance binding affinity for the target protein and E3 ligase, improve pharmacokinetic properties, increase cell permeability and stability, and reduce off-target effects. This leads to more efficient induction of target protein degradation, providing strong support for the development of targeted therapeutics.

Fig 2. Strategic design of oral PROTAC degraders for CDK2/4/6. (Han X, et al., 2022)

Our Services

CD ComputaBio offers structural optimization services for PROTAC molecules, aiming to enhance their targeting, cell permeability, ternary complex formation efficiency, degradation activity, pharmacokinetic properties, and safety, providing comprehensive customized modification strategies for your PROTAC drug development projects.

We offer service to modify PROTAC degraders to target different receptors, including but not limited to:

Targeting nuclear receptors: AR, ER, RAR, etc.
Targeting protein kinases: Akt, BCR, c-Abl, BTK, ALK, CDK9, RIPK2, DAPK1, PSD-95, etc.
Targeting transcriptional regulatory proteins: BRD4, Sirt2, HDAC6, TRIM24, IKZF1/3, Smad3, etc.
Targeting regulatory proteins: CRABP-I/II, TACC3, AHR, FKBP12, ERRα, X-protein, etc.
Targeting neurodegenerative related proteins: Huntingtin, Tau, α-synuclein, etc.
Targeting cellular metabolic enzymes: MetAP-2, DHODH, etc.

Strategies for PROTAC Structure Modification

Target Protein Ligand Modification

Through structure-activity relationship (SAR) studies and simulations, provide more effective ligand modifications to enhance their binding affinity with the target protein, thereby improving the degradation efficiency of PROTACs.

Linker Optimization

CD ComputaBio utilizes computational simulation technologies to optimize the design of linkers in terms of length, flexibility, and chemical properties, aiming to enhance the efficacy, stability, and targeting ability of drugs.

Our Advantages

Experienced Team - Our team possesses profound professional knowledge and extensive project experience.
Customized Solutions - We understand the uniqueness of each project and offer tailor-made service plans to meet the specific needs of our clients.
Confidentiality and Compliance - We strictly adhere to data protection regulations and industry standards, safeguarding our clients' intellectual property and privacy.

If you are interested in the structural design and computational simulation of PROTACs, please feel free to contact the professional team at CD ComputaBio. By integrating computational biology approaches, we hope to accelerate the research and development and application of PROTACs, providing novel therapeutic strategies for refractory diseases.

References:

Vetma, V.; et al. Development of PROTAC degrader drugs for cancer[J]. Annual Review of Cancer Biology. 2024, 9.
Han, X.; Sun Y. Strategies for the discovery of oral PROTAC degraders aimed at cancer therapy[J]. Cell Reports Physical Science. 2022, 3(10).

* For Research Use Only.

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