PROTAC Building Blocks: Precision Tools to Targeted Protein Degradation

Q: What services does Alfa Chemistry offer for PROTAC research?

Alfa Chemistry provides off-the-shelf PROTAC building blocks (warheads, linkers, E3 ligands, and conjugates) as well as custom synthesis of PROTACs and intermediates. We also offer PROTAC-focused library synthesis and assay development through our discovery services. Researchers can browse products on our catalog and request technical support or custom projects via contact.

Accelerating PROTAC Drug Development Through Precision Chemistry

PROTACs (Proteolysis Targeting Chimeras) represent a breakthrough in Targeted Protein Degradation, enabling the destruction of disease-causing proteins previously deemed "undruggable." Unlike traditional inhibitors, these bifunctional protein degraders hijack the ubiquitin-proteasome system via a unique PROTAC mechanism.

At , we provide the foundational elements—high-purity PROTAC Building Blocks—that empower researchers to accelerate the development of these groundbreaking therapeutic agents. Our comprehensive collection covers all critical components required to construct efficient and selective PROTAC molecules.

Online Inquiry View Products

OverviewProductsServicesAdvantagesReviewsFAQsFrontier UpdateContact Form

What Are PROTACs?

PROTACs are heterobifunctional small molecules that harness the cell's ubiquitin–proteasome system to induce targeted protein degradation. Each PROTAC links a ligand for a protein-of-interest (POI) to an E3 ligase ligand via a chemical linker. By bringing the target and an E3 ubiquitin ligase into close proximity, PROTACs trigger ubiquitination and subsequent proteasomal destruction of the POI. This mechanism enables removal of disease-causing proteins – including kinases, transcription factors and "undruggable" scaffolds – instead of merely inhibiting them. For example, PROTACs have been developed to degrade a wide range of targets, including BTK, BRD4, AR, ER, STAT3, and tau proteins.

Schematic diagram of how PROTAC induces proteasomal degradation of its target protein.

Schematic diagram of PROTAC mechanism of action (Kelm, Jeremy M., et al., 2023)

Structural Components: The Architecture of Protein Degradation

Leverage 's Largest In-Stock Portfolio to Accelerate Your PROTAC Development

E3 Ligase Ligands: The Degradation Initiators

Linkers: The Spatial Orchestrators

Target Protein Binders: Precision Warheads

Bifunctional Conjugates: Pre-assembled Intermediates

E3 Ligase Ligands: The Degradation Initiators

E3 ubiquitin ligases serve as the molecular machinery that tags target proteins for destruction. Our building blocks feature diverse, high-affinity ligands for key E3 ligases:

CRBN (Cereblon) Binders: Including lenalidomide derivatives and structural analogs optimized for cereblon binding affinity.
VHL (Von Hippel-Lindau) Recruiters: Hydroxyproline-based ligands with enhanced binding specificity.
MDM2 and IAP Ligands: Expanding the range of E3 ligases for tissue-specific targeting.

E3 Ligase Ligand

Featured Products

CAS No.	Product Name	Price
1229705-06-9	4-[(3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine-2-amido]-3-methoxybenzoic acid	Inquiry
174649-04-8	benzyl 4-(4-(2,4-dioxo-1,3-diazan-1-yl)phenyl)piperazine-1-carboxylate	Inquiry
1797406-78-0	(2S,4S)-1-[(2S)-2-amino-3,3-dimethylbutanoyl]-4-hydroxy-N-[(4-(4-methyl-1,3-thiazol-5-yl)phenyl)methyl]pyrrolidine-2-carboxamide	Inquiry
2154342-18-2	tert-butyl N-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl)piperidin-4-yl)carbamate	Inquiry
2154357-09-0	tert-butyl 4-[(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl)amino]piperidine-1-carboxylate	Inquiry

Linkers: The Spatial Orchestrators

Linkers determine the precise spatial orientation required for ternary complex formation. Linker length, flexibility and composition significantly affect PROTAC performance. We offer chemically diverse linker systems:

PEG-Based Chains: Improving solubility and reducing aggregation (various lengths from 3 to 12 units).
Alkyl and Alkyl/Ether Chains: Enhancing membrane permeability and metabolic stability.
Rigid Cyclic Structures: Reducing conformational entropy for improved complex formation.
Responsive Linkers: Cleavable connectors for tumor microenvironment-specific activation (GSH, pH, or ROS-responsive).

PROTAC Linker

Featured Products

CAS No.	Product Name	Price
1248684-56-1	(1-[(3-bromophenyl)methyl]piperidin-4-yl)methanol	Inquiry
1310478-81-9	ethyl 2-oxo-1-azaspiro[4.5]decane-8-carboxylate	Inquiry
1590372-81-8	8,11-dioxadispiro[3.2.4^{7}.2^{4}]tridecan-2-ol	Inquiry
1609545-83-6	4-(dibenzylamino)-3-fluoro-2-methylbutan-2-ol	Inquiry
163210-40-0	tert-butyl 4-(2-hydroxyethoxy)piperidine-1-carboxylate	Inquiry

Target Protein Binders: Precision Warheads

These are ligands or inhibitors that bind the POI. They are typically derived from known small-molecule inhibitors or natural ligands of the target. Our library includes ligands targeting key disease-associated proteins:

Kinase inhibitors (BTK, EGFR, CDKs)
Nuclear receptor binders (AR, ER)
Epigenetic regulators (BET bromodomains)
Customizable warheads for novel targets

PROTAC Library

Featured Products

CAS No.	Product Name	Price
1013938-03-8	(2S)-2-(3-chloropropyl)pent-4-en-1-ol	Inquiry
1014613-40-1	2-hydroxy-S-(4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethane-1-sulfonamido	Inquiry
1037681-49-4	1-[(4-methoxyphenyl)methyl]piperidine-2,6-dione	Inquiry
105174-49-0	4-chloro-1-(2,4-dihydroxyphenyl)butan-1-one	Inquiry
1061605-21-7	2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetic acid	Inquiry

Bifunctional Conjugates: Pre-assembled Intermediates

These are partially built fragments, such as an E3 ligand already attached to a linker or a warhead-linker conjugate. Using bifunctional intermediates can streamline synthesis. For example, E3 Ligand–Linker conjugates (e.g. CRBN-PEG or VHL-linker compounds) and Warhead–Linker intermediates can be purchased from . These precursors accelerate PROTAC assembly by avoiding repetitive linker attachment steps. 's product list includes ready-to-use conjugates for common PROTAC combinations:

Target Protein Ligand-Linker Conjugates
E3 Ligase Ligand-Linker Conjugates

E3 Ligase Ligand-Linker

Featured Products

CAS No.	Product Name	Price
2154342-30-8	5-[(3-aminopropyl)(methyl)amino]-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione	Inquiry
2172819-72-4	4-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-4-oxobutanoic acid	Inquiry
2172819-73-5	5-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-5-oxopentanoic acid	Inquiry
2172819-74-6	6-(((R)-1-((2R,4S)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-6-oxohexanoic acid	Inquiry
2172820-08-3	2-(2-(2-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-2-oxoethoxy)ethoxy)acetic acid	Inquiry

PROTAC Services & Solutions: End-to-End Development Platform

Beyond Building Blocks: Comprehensive Support for Your Protein Degradation Pipeline

's PROTAC Development Platform delivers integrated solutions from concept to preclinical candidates. Leverage our expertise to accelerate your targeted protein degradation programs:

PROTAC Service PROTACs Development Platform

Computational PROTAC Design:

Ternary complex modeling (E3 ligase-linker-target)
Binding affinity prediction for POI/E3 interfaces

Hook Effect Mitigation Strategies:

Linker length/rigidity optimization
Affinity balancing for stable ternary complexes

In Vivo PK/PD Modeling:

LogP/logD optimization for bioavailability
Tissue distribution simulations

PROTAC Design & Optimization

Rational Engineering for Enhanced Degradation Efficiency

Bifunctional PROTAC Assembly:

High-yield conjugation (warhead-linker-E3 ligand)
Chiral center preservation

Specialized Scaffolds:

Tumor-activated prodrugs
Cell-penetrating peptide conjugates

Batch Consistency:

≥98% purity (HPLC/LC-MS verified)
ISO 9001-certified facilities

PROTAC Custom Synthesis

Complex Molecule Expertise (0.1 mg to 100 g scale)

Biophysical Characterization:

SPR/BLI binding kinetics (target/E3 engagement)
DSF target engagement verification

Functional Assessment:

Cellular degradation (DC₅₀, Dmax)
Hook effect concentration profiling
Ubiquitinylation kinetics (Western/MS)

In Vitro ADME:

Metabolic stability (microsomes/hepatocytes)
Permeability (PAMPA/Caco-2)

PROTAC Characterization & Evaluation

IND-Enabling Data Packages

Why ?

Purity

>95% (typically >98% by HPLC/LCMS)

Catalog Breadth

500+ compounds covering CRBN, VHL, IAP, MDM2 ligands and diverse linkers

Functionalization

Ready-to-conjugate groups: acids, amines, alkynes, azides, Boc/Cbz protection

Structural Diversity

Includes PEG, alkyl, piperazine, spirocycle, and heterocyclic scaffolds

Custom Synthesis

Available for bespoke building blocks

What Our Clients Say

"We've sourced several PROTAC linkers and E3 ligase ligands from for our protein degradation studies. The purity and batch-to-batch consistency are excellent, and their technical support is always prompt and insightful."

Dr. Emma Li

Department of Biochemistry

"'s tumor-activated linker enabled our hypoxia-responsive PROTAC to achieve 10-fold higher selectivity in solid tumor models. The GSH-cleavable design degraded KRAS G12D at DC50 = 15 nM in hypoxic zones while sparing normal tissues – resolving our off-target toxicity bottleneck."

Dr. H. Schmidt

Oncology Discovery Team

"The PROTAC intermediates from performed exceptionally well in our in-house conjugation assays. Their availability of functionalized warheads and linkers saved us weeks of synthesis and optimization."

Jason Wu

Synthetic Chemist

FAQs About PROTACs

What is the "hook effect" or concentration-dependent degradation?

PROTACs often show a bell-shaped dose–response curve. At very high concentrations, each PROTAC may saturate binding to either the target or the E3 ligand without forming the ternary complex. This reduces degradation efficacy – a phenomenon known as the hook effect. Optimal dosing must balance PROTAC concentration to avoid this effect.

provides linker length/rigidity guidance and affinity-optimized E3 ligands to maintain ternary complex stability at high concentrations.

How does a PROTAC differ from a molecular glue?

Molecular glues are monovalent small molecules that induce protein–protein interactions between a target and an E3 ligase. PROTACs are bivalent, with separate binding arms for the target and the E3. In practice, glues are smaller and simpler, whereas PROTACs offer modular design of linkers and two ligands.

Our building blocks enable bifunctional PROTAC design, while also offering components for molecular glue development.

What services does offer for PROTAC research?

provides off-the-shelf PROTAC building blocks (warheads, linkers, E3 ligands, and conjugates) as well as custom synthesis of PROTACs and intermediates. We also offer PROTAC-focused library synthesis and assay development through our discovery services. Researchers can browse products on our catalog and request technical support or custom projects via contact.

Are PROTACs being developed into drugs?

Yes. PROTACs are an emerging drug modality. Several PROTAC candidates have entered clinical trials, particularly in oncology. For instance, ARV-110 and ARV-471 (which recruit CRBN) have shown efficacy in Phase II trials. The field is rapidly evolving, with ongoing research into optimizing PROTAC design for safety and oral bioavailability. [2]

Cutting-Edge Update: Latest Advances in PROTAC Technology (2025)

(Cornu, Marie, et al., 2025)

PROTAC technology has made significant strides with the introduction of activated PROTACs, offering improved selectivity and reduced off-target effects. Innovations such as light-activated PROTACs (e.g., Popto-dBET1), enzyme-activated PROTACs (e.g., Ha-PROTAC), and ROS-activated PROTACs leverage specific environmental cues, like light, enzymes, and reactive oxygen species, to activate PROTACs selectively in target tissues. Additionally, dual-target PROTACs enable simultaneous degradation of two proteins, enhancing therapeutic potential. New strategies like macrocyclic PROTACs improve bioactivity and pharmacokinetics by stabilizing molecular conformation, while self-assembly PROTACs and nanoPROTACs combine PROTAC technology with nanotechnology to enhance delivery and targeting. Furthermore, antibody-conjugated PROTACs (DAC-PROTACs) combine PROTACs with antibody-drug conjugates (ADC), allowing precise tissue targeting and reducing off-target toxicity. These innovations open new avenues for more efficient and targeted therapies in treating complex diseases. [3]

Contact & Ordering

Ready to streamline your pharmaceutical development? Unlock the full potential of your PROTAC projects with 's cutting-edge solutions.

References

Kelm, Jeremy M., et al. Molecular Cancer, 2023, 22(1), 62.
Liu, Zi, et al. Molecular biomedicine, 2022, 3(1), 46.
Cornu, Marie, et al. Drug Discovery Today, 2025, 30(6), 104376.