PROTACs or Proteolysis Targeting Chimeric Molecules are heterobifunctional nanomolecules that theoretically target any protein for ubiquitination and degradation. In terms of the structure, PROTACs consist of one moiety which is recognized by the E3 ligase. This moiety is then chemically and covalently linked to a small molecule or a protein that recognizes the target protein. The trimeric complex formation leads to the transfer of ubiquitins to the target protein.

By removing target proteins directly rather than merely blocking them, PROTACs can provide multiple advantages over small molecule inhibitors, which can require high systemic exposure to achieve sufficient inhibition, often resulting in toxic side effects and eventual drug resistance. PROTAC molecules possess good tissue distribution and the ability to target intracellular proteins, thus can be directly applied to cells or injected into animals without the use of vectors.

Targeted protein degradation using the PROTAC technology is emerging as a novel therapeutic method to address diseases, such as cancer, driven by the aberrant expression of a disease-causing protein. In addition to the use of PROTACs for the treatment of human disease, these molecules provide a chemical genetic approach to “knock down” proteins to study their function. Currently, there are several small molecule inhibitors that have been found to show good biological activity by specifically targeting BET, estrogen receptor (ER), androgen receptor, etc.

References:
[1] Sakamoto KM. Pediatr Res. 2010 May;67(5):505-8.
[2] Neklesa TK, et al. Pharmacol Ther. 2017 Jun;174:138-144.


Anti-infection >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
ADC Cytotoxin ADC Linker Drug-Linker Conjugates for ADC PROTAC-linker Conjugate for PAC
Apoptosis >
Apoptosis Bcl-2 Family c-Myc Caspase DAPK Ferroptosis IAP MDM-2/p53 PKD RIP kinase Survivin Thymidylate Synthase TNF Receptor
Autophagy >
Autophagy LRRK2 ULK Mitophagy
Cell Cycle/DNA Damage >
Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
Cytoskeleton >
Arp2/3 Complex Dynamin Gap Junction Protein Integrin Kinesin Microtubule/Tubulin Mps1 Myosin PAK
Epigenetics >
AMPK Aurora Kinase DNA Methyltransferase Epigenetic Reader Domain HDAC Histone Acetyltransferase Histone Demethylase Histone Methyltransferase JAK MicroRNA PARP PKC Sirtuin Protein Arginine Deiminase
GPCR/G Protein >
5-HT Receptor Adenosine Receptor Adenylate Cyclase Adiponectin Receptor Adrenergic Receptor Angiotensin Receptor Bombesin Receptor Bradykinin Receptor Cannabinoid Receptor CaSR CCR CGRP Receptor Cholecystokinin Receptor CRFR CXCR Dopamine Receptor EBI2/GPR183 Endothelin Receptor GHSR Glucagon Receptor Glucocorticoid Receptor GNRH Receptor GPCR19 GPR109A GPR119 GPR120 GPR139 GPR40 GPR55 GPR84 Guanylate Cyclase Histamine Receptor Imidazoline Receptor Leukotriene Receptor LPL Receptor mAChR MCHR1 (GPR24) Melatonin Receptor mGluR Motilin Receptor Neurokinin Receptor Neuropeptide Y Receptor Neurotensin Receptor Opioid Receptor Orexin Receptor (OX Receptor) Oxytocin Receptor P2Y Receptor Prostaglandin Receptor Protease-Activated Receptor (PAR) Ras RGS Protein Sigma Receptor Somatostatin Receptor TSH Receptor Urotensin Receptor Vasopressin Receptor Melanocortin Receptor
Immunology/Inflammation >
Aryl Hydrocarbon Receptor CCR Complement System COX CXCR FLAP Histamine Receptor IFNAR Interleukin Related IRAK MyD88 NO Synthase NOD-like Receptor (NLR) PD-1/PD-L1 PGE synthase Salt-inducible Kinase (SIK) SPHK STING Thrombopoietin Receptor Toll-like Receptor (TLR) Arginase
JAK/STAT Signaling >
EGFR JAK Pim STAT
MAPK/ERK Pathway >
ERK JNK KLF MAP3K MAP4K MAPKAPK2 (MK2) MEK Mixed Lineage Kinase MNK p38 MAPK Raf Ribosomal S6 Kinase (RSK)
Membrane Transporter/Ion Channel >
ATP Synthase BCRP Calcium Channel CFTR Chloride Channel CRAC Channel CRM1 EAAT2 GABA Receptor GlyT HCN Channel iGluR Monoamine Transporter Monocarboxylate Transporter Na+/Ca2+ Exchanger Na+/HCO3- Cotransporter Na+/K+ ATPase nAChR NKCC P-glycoprotein P2X Receptor Potassium Channel Proton Pump SGLT Sodium Channel TRP Channel URAT1
Metabolic Enzyme/Protease >
15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
Neuronal Signaling >
5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
NF-κB >
NF-κB IKK Keap1-Nrf2 MALT1
PI3K/Akt/mTOR >
Akt AMPK ATM/ATR DNA-PK GSK-3 MELK mTOR PDK-1 PI3K PI4K PIKfyve PTEN
PROTAC >
PROTAC E3 Ligase Ligand-Linker Conjugate Ligand for E3 Ligase PROTAC Linker PROTAC-linker Conjugate for PAC
Protein Tyrosine Kinase/RTK >
Ack1 ALK Bcr-Abl BMX Kinase Btk c-Fms c-Kit c-Met/HGFR Discoidin Domain Receptor DYRK EGFR Ephrin Receptor FAK FGFR FLT3 IGF-1R Insulin Receptor IRAK Itk PDGFR PKA Pyk2 ROS Src Syk TAM Receptor Trk Receptor VEGFR
Stem Cell/Wnt >
Casein Kinase ERK Gli GSK-3 Hedgehog Hippo (MST) JAK Notch Oct3/4 PKA Porcupine ROCK sFRP-1 Smo STAT TGF-beta/Smad Wnt YAP β-catenin γ-secretase
TGF-beta/Smad >
TGF-beta/Smad PKC ROCK TGF-β Receptor
Vitamin D Related >
VD/VDR
Others >
Androgen Receptor Aromatase Estrogen Receptor/ERR Progesterone Receptor Thyroid Hormone Receptor Others

DBCO-PEG1-NHS ester

DBCO-PEG1-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2228857-34-7
  • MF: C28H27N3O7
  • MW: 517.53
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MS-PEG3-THP

MS-PEG3-THP is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 357204-84-3
  • MF: C12H24O7S
  • MW: 312.38
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG3-OMs

m-PEG3-OMs is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 74654-05-0
  • MF: C8H18O6S
  • MW: 260.30500
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

E3 ligase Ligand-Linker Conjugates 39

E3 ligase Ligand-Linker Conjugates 39 incorporates a cIAP ligand for the E3 ubiquitin ligase, and a PROTAC linker. E3 ligase Ligand-Linker Conjugates 39 can be used to design PROTAC degrader[1].

  • CAS Number: 2113688-20-1
  • MF: C37H55N5O8S
  • MW: 729.93
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Methyl-PEG9-bromide

m-PEG9-Br is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 125562-30-3
  • MF: C19H39BrO9
  • MW: 491.412
  • Catalog: PROTAC Linker
  • Density: 1.2±0.0 g/cm3
  • Boiling Point: 498.1±0.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 208.4±0.0 °C

Azdo-PEG3-S-PEG3-Azide

Azido-PEG3-S-PEG3-azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2055023-77-1
  • MF: C16H32N6O6S
  • MW: 436.53
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC CRBN Degrader-1

PROTAC CRBN Degrader-1 comprises a cereblon (CRBN) ligand binding group, a linker and an von Hippel-Landau (VHL) binding group. PROTAC CRBN Degrader-1 is an cereblon (CRBN) degrader[1].

  • CAS Number: 2358775-70-7
  • MF: C53H72N8O13S
  • MW: 1061.25
  • Catalog: PROTAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Biotinyl-NH-PEG3-C3-amido-C3-COOH

Biotinyl-NH-PEG3-C3-amido-C3-COOH is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1202761-21-4
  • MF: C25H44N4O8S
  • MW: 560.70
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fmoc-NMe-PEG4-NHS este

Fmoc-NMe-PEG4-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2228857-30-3
  • MF: C31H38N2O10
  • MW: 598.64
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aminooxy-PEG2-azide

Aminooxy-PEG2-azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1]. Aminooxy-PEG2-azide is also a non-cleavable 2 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[2].

  • CAS Number: 1043426-13-6
  • MF: C6H14N4O3
  • MW: 190.20
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Propargyl-PEG6-Ms

Propargyl-PEG5-Ms is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1036204-62-2
  • MF: C14H26O8S
  • MW: 354.42
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R)-TCO-OH

(R)-TCO-OH is an alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 39637-78-0
  • MF: C8H14O
  • MW: 126.20
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Br-C3-methyl ester

Br-C3-methyl ester is a Alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTAC PD-1/PD-L1 degrader-1 (HY-131183)[1].

  • CAS Number: 4897-84-1
  • MF: C5H9BrO2
  • MW: 181.028
  • Catalog: PROTAC Linker
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 186.5±0.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 87.0±13.0 °C

(S,R,S)-AHPC-Me-C6-NH2

(S,R,S)-AHPC-Me-C6-NH2 is a PROTAC building block.

  • CAS Number: 2411422-49-4
  • MF: C30H45N5O4S
  • MW: 571.78
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bromo-PEG2-acetic acid

Bromo-PEG2-acetic acid is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2409962-85-0
  • MF: C6H11BrO4
  • MW: 227.05
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC Bcl-xL degrader-3

PROTAC Bcl-xL degrader-3 is a potent ROTAC Bcl-xL degrader (WO2020163823A2, compound 44)[1].

  • CAS Number: 2471970-60-0
  • MF: C82H105ClF3N11O11S4
  • MW: 1641.49
  • Catalog: Bcl-2 Family
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Boc-N-bis(PEG4-azide)

N-Boc-N-bis(PEG4-azide) is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2055041-25-1
  • MF: C25H49N7O10
  • MW: 607.70
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PEG4-bis(phosphonic acid diethyl ester)

PEG4-bis(phosphonic acid diethyl ester) is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 106338-06-1
  • MF: C16H36O11P2
  • MW: 466.4
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hydroxy-PEG2-methyl ester

Hydroxy-PEG2-C2-methyl ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 457897-73-3
  • MF: C8H16O5
  • MW: 192.21
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-(azide-PEG3)-N'-(Mal-PEG4)-Cy5

N-(azide-PEG3)-N'-(Mal-PEG4)-Cy5 is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2107273-74-3
  • MF: C50H68ClN7O10
  • MW: 962.57
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NH2-PEG6-Boc

NH2-PEG6-Boc is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1]. NH2-PEG6-Boc is also a non-cleavable 6 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[2].

  • CAS Number: 1286281-32-0
  • MF: C19H39NO8
  • MW: 409.51500
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S,R,S)-AHPC-C2-PEG3-BCN

(S,R,S)-AHPC-C2-PEG3-BCN (Compound 16b) is a VHL ligand, and can be used for synthesis of PROTACs[1].

  • CAS Number: 2876198-36-4
  • MF: C42H59N5O9S
  • MW: 810.01
  • Catalog: Ligand for E3 Ligase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lenalidomide-5-Br

Lenalidomide-5-Br is the Lenalidomide-based cereblon (CRBN) ligand used in the recruitment of CRBN protein. Lenalidomide-5-Br can be connected to the ligand for protein by a linker to form PROTAC[1].

  • CAS Number: 1010100-26-1
  • MF: C13H11BrN2O3
  • MW: 323.14
  • Catalog: Ligand for E3 Ligase
  • Density: 1.688±0.06 g/cm3
  • Boiling Point: 587.6±50.0 °C
  • Melting Point: N/A
  • Flash Point: N/A

DNP-PEG4-NHS ester

DNP-PEG4-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 858126-78-0
  • MF: C21H28N4O12
  • MW: 528.46700
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG3-azide

m-PEG3-azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 74654-06-1
  • MF: C7H15N3O3
  • MW: 189.21200
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Propargyl-PEG9-amine

Propargyl-PEG9-amine is a PEG-based PROTAC linker can be used in the synthesis of PROTACs.

  • CAS Number: 2093153-98-9
  • MF: C21H41NO9
  • MW: 451.55
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H2n-peg13-ch2ch2nh2

Amino-PEG13-amine is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1228119-65-0
  • MF: C28H60N2O13
  • MW: 632.78
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Thiol-C10-amide-PEG8

Thiol-C10-amide-PEG8 is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1353948-95-4
  • MF: C27H55NO9S
  • MW: 569.79
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Biotin-C1-PEG3-C3-amine TFA

Biotin-C1-PEG3-C3-amine (TFA) is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1334172-59-6
  • MF: C22H39F3N4O7S
  • MW: 560.63
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Thalidomide-4-NH-PEG2-COO(t-Bu)

Thalidomide-4-NH-PEG2-COO(t-Bu) is a t-Bu modified Thalidomide (HY-14658), which acts as a Cereblon ligand to recruit CRBN protein. The t-Bu protecting group at the end of Thalidomide-4-NH-PEG2-COO(t-Bu) can be removed under acidic conditions to participate in the synthesis of PROTAC molecules. Thalidomide-4-NH-PEG2-COO(t-Bu) is a key intermediate in the synthesis of CRBN-based PROTAC molecules.

  • CAS Number: 2140807-16-3
  • MF: C24H31N3O8
  • MW: 489.52
  • Catalog: Ligand for E3 Ligase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A