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

Pomalidomide-C3-NH2 hydrochloride

Pomalidomide-C3-NH2 hydrochloride is a synthesized E3 ligase ligand-linker conjugate that incorporates the Pomalidomide based cereblon ligand and a linker used in PROTAC technology[1].

  • CAS Number: 2154342-45-5
  • MF: C16H19ClN4O4
  • MW: 366.80
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Methyltetrazine-PEG5-NHS ester

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

  • CAS Number: 1802907-92-1
  • MF: C24H31N5O9
  • MW: 533.53
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

mPEG16-Br

m-PEG16-Br is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1238189-11-1
  • MF: C33H67BrO16
  • MW: 799.78
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC CYP1B1 degrader-1

PROTAC CYP1B1 degrader-1 (Compound 6C), a α-naphthoflavone chimera derivative, is able to eliminate cytochrome P450 (CYP)1B1-mediated drug resistance via targeted CYP1B1 degradation, with IC50s of 95.1 and 9838.6 nM for CYP1B1 and CYP1A2, respectively. PROTAC CYP1B1 degrader-1 can be used for the research of CYP1B1-overexpressing prostate cancer[1].

  • CAS Number: 2411389-67-6
  • MF: C43H39N5O10
  • MW: 785.80
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

t-Boc-N-Amido-PEG5-propargyl

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

  • CAS Number: 2062663-67-4
  • MF: C18H33NO7
  • MW: 375.46
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azido-PEG10-acid

Azido-PEG10-acid is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tos-PEG12-Tos

Tos-PEG12-Tos is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1456708-45-4
  • MF: C38H62O17S2
  • MW: 855.019
  • Catalog: PROTAC Linker
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 833.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 457.8±34.3 °C

Biotin-PEG2-C4-alkyne

Biotin-PEG2-C4-alkyne is a PEG-based PROTAC linker can be used in the synthesis of PROTACs.

  • CAS Number: 1011268-28-2
  • MF: C22H36N4O5S
  • MW: 468.610
  • Catalog: PROTAC Linker
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 799.8±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 437.5±32.9 °C

Fmoc-N-amido-PEG2-alcohol

Fmoc-N-amido-PEG2-alcohol is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 299430-87-8
  • MF: C19H21NO4
  • MW: 327.37400
  • Catalog: PROTAC Linker
  • Density: 1.221g/cm3
  • Boiling Point: 547.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 285.1ºC

N-(Amino-PEG4)-N-Biotin-PEG4-acid

N-(Amino-PEG4)-N-Biotin-PEG4-acid is a biotin-labeled, PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2100306-84-9
  • MF: C31H58N4O12S
  • MW: 710.88
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acid-PEG2-C2-Boc

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

  • CAS Number: 2086688-99-3
  • MF: C12H22O6
  • MW: 262.3
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mal-PEG24-NHS ester

Mal-PEG24-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2226733-37-3
  • MF: C16H19N3O8
  • MW: 381.34
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cl-PEG6-acid

Cl-PEG6-acid is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2365309-92-6
  • MF: C14H27ClO8
  • MW: 358.81
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(+)-Biotin-ONP

(+)-Biotin-ONP is an alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 33755-53-2
  • MF: C16H19N3O5S
  • MW: 365.404
  • Catalog: PROTAC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 642.9±50.0 °C at 760 mmHg
  • Melting Point: 163-165ºC
  • Flash Point: 342.6±30.1 °C

Bromo-PEG3-THP

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

  • CAS Number: 220568-33-2
  • MF: C11H21BrO4
  • MW: 297.19
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fmoc-amino-PEG3-CH2COOH

Fmoc-amino-PEG3-CH2COOH is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 139338-72-0
  • MF: C23H27NO7
  • MW: 429.463
  • Catalog: PROTAC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 651.1±65.0 °C at 760 mmHg
  • Melting Point: 46℃
  • Flash Point: 347.6±34.3 °C

Tz-Thalidomide

Tz-Thalidomide is a tetrazine tagged Thalidomide (HY-14658) (Ligands for E3 Ligase). Tz-Thalidomide has binding affinity for BRD4, with IC50s of 46.25 μM (BRD4-1) and 62.55 μM (BRD4-2)[1].

  • CAS Number: 2087490-42-2
  • MF: C29H29N7O6
  • MW: 571.58
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2,5-Dioxopyrrolidin-1-yl 2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaheptadecan-17-oate

Boc-NH-PEG3-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2250216-93-2
  • MF: C18H30N2O9
  • MW: 418.44
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG7-4-nitrophenyl carbonate

m-PEG7-4-nitrophenyl carbonate is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 678150-56-6
  • MF: C20H31NO11
  • MW: 461.46
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Methyl azetidine-3-carboxylate hydrochloride

Methyl azetidine-3-carboxylate hydrochloride is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Methyl azetidine-3-carboxylate hydrochloride is also a alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs<

  • CAS Number: 100202-39-9
  • MF: C5H10ClNO2
  • MW: 151.591
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: 190.9ºC at 760 mmHg
  • Melting Point: 93.0 to 97.0 °C
  • Flash Point: 69.3ºC

(S,R,S)-AHPC-C5-NH2

(S,R,S)-AHPC-C5-NH2 (VH032-C5-NH2) is a synthesized E3 ligase ligand-linker conjugate that incorporates the VH032 based VHL ligand and a linker used for estrogen-related receptor α (ERRα) PROTAC degrader[1].

  • CAS Number: 2170695-19-7
  • MF: C28H41N5O4S
  • MW: 543.72
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

E3 ligase Ligand 6

Protein degrader 1 TFA is a small molecule ligand for VHL, an E3 ligase which has been targeted in numerous PROTACs.

  • CAS Number: 1631137-51-3
  • MF: C24H31F3N4O5S
  • MW: 544.59
  • Catalog: Ligand for E3 Ligase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

M-Peg3-sulfone-peg2-oh

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

  • CAS Number: 1919045-00-3
  • MF: C13H28O8S
  • MW: 344.42
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CD147 degrader 1

CD147 degrader 1 is a PROTAC targets CD147 with an DC50 value of 6.72 µM. CD147 degrader 1 inhibits cell proliferation, migration and invasion. CD147 degrader 1 decreases the expression of CD147, MMP9, and p-STAT3 protein. CD147 degrader 1 shows anti-cancer acyivity[1].

  • CAS Number: 2416740-37-7
  • MF: C38H42N4O11
  • MW: 730.76
  • Catalog: PROTAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Benzyl-PEG5-azide

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

  • CAS Number: 86770-72-1
  • MF: C17H27N3O5
  • MW: 353.413
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NH2-C4-NH-Boc

NH2-C4-NH-Boc (compound 15) is a PROTAC linker, which refers to the Alkyl/ether composition. NH2-C4-NH-Boc can be used in the synthesis of a series of PROTACs. PROTACs contain two different ligands connected by a linker; one is a ligand for an E3 ubiquitin ligase and the other is for the target protein. PROTACs exploit the intracellular ubiquitin-proteasome system to selectively degrade target proteins[1].

  • CAS Number: 68076-36-8
  • MF: C9H20N2O2
  • MW: 188.267
  • Catalog: PROTAC Linker
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 292.9±23.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 130.9±22.6 °C

Azido-PEG3-C-Boc

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

  • CAS Number: 172531-36-1
  • MF: C12H23N3O5
  • MW: 289.32800
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Methylamino-PEG2-acid HCl

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

  • CAS Number: 1807503-87-2
  • MF: C8H17NO4
  • MW: 191.225
  • Catalog: PROTAC Linker
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 310.2±27.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 141.4±23.7 °C

Azido-PEG12-NHS ester

Azido-PEG12-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2363756-50-5
  • MF: C31H56N4O16
  • MW: 740.79
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cl-C6-PEG4-O-CH2COOH

PROTAC Linker 4 is a PROTAC linker can be used in the synthesis of chloroalkane-containing PROTACs (HaloPROTACs).

  • CAS Number: 1799506-30-1
  • MF: C16H31ClO7
  • MW: 370.87
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A