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.


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Bis-PEG2-Boc

Bis-PEG2-Boc is an alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1611468-28-0
  • MF: C16H30O6
  • MW: 318.41
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S,R,S)-AHPC-C8-NH2 (hydrochloride)

(S,R,S)-AHPC-C7-NH2 hydrochloride (VH032-C7-NH2 hydrochloride) is a synthesized E3 ligase ligand-linker conjugate that incorporates the VH032 based VHL ligand and a linker used for AKT PROTAC degrader. (S,R,S)-AHPC-C7-NH2 hydrochloride is XF038-164A, example 8, extracted from patent WO2019173516A1[1].

  • CAS Number: 2376139-49-8
  • MF: C31H48ClN5O4S
  • MW: 622.26
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Thalidomide-PEG3-NH2

Thalidomide-PEG3-NH2 is a synthesized E3 ligase ligand-linker conjugate that incorporates the Thalidomide based cereblon ligand and a linker used in PROTAC technology[1].

  • CAS Number: 1957236-10-0
  • MF: C19H23N3O7
  • MW: 405.40
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PEG3-C4-OBn

PEG3-C4-OBn is a polyethylene glycol (PEG)-based PROTAC linker. PEG3-C4-OBn can be used in the synthesis of the PROTAC SGK3 degrader-1 (HY-125878). PROTAC SGK3 degrader-1 is a potent SKG3 degrader based on PROTAC[1][2].

  • CAS Number: 2381196-79-6
  • MF: C17H28O4
  • MW: 296.40
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1,3-bis(carboxyethoxy)-2,2-bis(carboxyethoxy)propane

1,3-bis(carboxyethoxy)-2,2-bis(carboxyethoxy)propane is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 35638-19-8
  • MF: C17H28O12
  • MW: 424.39700
  • Catalog: PROTAC Linker
  • Density: 1.355g/cm3
  • Boiling Point: 710.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 248.8ºC

QCA570

QCA570 is a potent BET degrader based on PROTAC, with an IC50 of 10 nM for BRD4 BD1 Protein.

  • CAS Number: 2207569-08-0
  • MF: C39H33N7O4S
  • MW: 695.798
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG11-acid

m-PEG11-acid is a non-cleavable 11 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1]. m-PEG11-acid is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[2].

  • CAS Number: 2280998-74-3
  • MF: C24H48O13
  • MW: 544.63
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-(t-Butoxycarbonylamido)-1,3-bis (t-butoxycarbonylethoxy)propane

C-NH-Boc-C-Bis-(C-PEG1-Boc) is an alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1807503-91-8
  • MF: C22H41NO8
  • MW: 447.56
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-(2,6-Dioxopiperidin-3-yl)-5-(prop-2-yn-1-yloxy)isoindoline-1,3-dione

Thalidomide-5-propargyl is a propargyl-modified Thalidomide (HY-14658), that acts as a Cereblon ligand to recruit CRBN proteins. Thalidomide-5-propargyl use alkynyl group at the end to be directly used in the synthesis of triazoles in the synthesis of PROTAC molecules, and is a key intermediate in the synthesis of PROTAC molecules based on CRBN design[1].

  • CAS Number: 2226303-74-6
  • MF: C16H12N2O5
  • MW: 312.28
  • Catalog: Ligand for E3 Ligase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NH2-PEG3 hydrochloride

NH2-PEG3 hydrochloride is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 92505-84-5
  • MF: C6H16ClNO3
  • MW: 185.64900
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

t-Boc-Aminooxy-PEG1-azide

Boc-Aminooxy-PEG1-azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2100306-67-8
  • MF: C9H18N4O4
  • MW: 246.26
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

XZ739

XZ739, a CRBN-dependent PROTAC BCL-XL degrader with a DC50 value of 2.5 nM in MOLT-4 cells after 16 h treatment. XZ739 also induces cell death through caspase-mediated apoptosis[1].

  • CAS Number: 2365172-19-4
  • MF: C65H76ClF3N8O12S3
  • MW: 1349.99
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

E3 ligase Ligand-Linker Conjugates 7 Free Base

E3 ligase Ligand-Linker Conjugates 7 Free Base is a synthesized compound that incorporates an E3 ligase ligand and a linker used in PROTAC technology.

  • CAS Number: 2010159-57-4
  • MF: C32H49N5O8S
  • MW: 663.83
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bromoacetamide-PEG3-propargyl

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

  • CAS Number: 932741-11-2
  • MF: C11H18BrNO4
  • MW: 308.17
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Boc-N-Amido-PEG3-azide

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

  • CAS Number: 642091-68-7
  • MF: C13H26N4O5
  • MW: 318.36900
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pomalidomide-amino-PEG3-NH2

Pomalidomide-amino-PEG3-NH2 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: 2380273-74-3
  • MF: C21H26N4O8
  • MW: 462.45
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

t-Boc-Aminooxy-PEG8-alcohol

t-Boc-Aminooxy-PEG8-alcohol is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2353410-14-5
  • MF: C21H43NO11
  • MW: 485.57
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tri(t-butoxycarbonylethoxymethyl) ethanol

Tri(t-butoxycarbonylethoxymethyl) ethanol is an alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1027581-61-8
  • MF: C26H48O10
  • MW: 520.65
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acid-PEG9-NHS ester

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

  • CAS Number: 1895916-27-4
  • MF: C26H45NO15
  • MW: 611.633
  • Catalog: PROTAC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 685.1±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 368.1±34.3 °C

t-Boc-N-amido-PEG2-C6-Cl

t-Boc-N-amido-PEG2-C6-Cl is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 920264-35-3
  • MF: C15H30ClNO4
  • MW: 323.86
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Propargyl-PEG2-beta-D-glucose

Propargyl-PEG2-beta-D-glucose is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2353409-73-9
  • MF: C13H22O8
  • MW: 306.31
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

endo-BCN-PEG4-NHS ester

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

  • CAS Number: 1807501-86-5
  • MF: C26H38N2O10
  • MW: 538.587
  • Catalog: PROTAC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG4-amino-Mal

m-PEG4-amino-Mal is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1263044-81-0
  • MF: C16H26N2O7
  • MW: 358.387
  • Catalog: PROTAC Linker
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 548.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 285.6±30.1 °C

Lenalidomide-OH

Lenalidomide-OH is an analog of cereblon (CRBN) ligand Lenalidomide for E3 ubiquitin ligase, and is used in the recruitment of CRBN protein. Lenalidomide-OH can be connected to the ligand for protein by a linker to form PROTACs, such as the PROTAC BTK degrader SJF620 (HY-133137)[1].

  • CAS Number: 1416990-08-3
  • MF: C13H12N2O4
  • MW: 260.25
  • Catalog: Ligand for E3 Ligase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aminooxy-PEG7-methane

Aminooxy-PEG7-methane is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1370698-27-3
  • MF: C15H33NO8
  • MW: 355.42
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tos-PEG6-CH2-Boc

Tos-PEG6-CH2-Boc is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1530777-90-2
  • MF: C25H42O11S
  • MW: 550.659
  • Catalog: PROTAC Linker
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 611.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 323.5±31.5 °C

Amino-PEG3-C2-Amine

Amino-PEG3-C2-Amine is a PEG-based (3 units) PROTAC linker can be used in the synthesis of PROTACs.

  • CAS Number: 929-75-9
  • MF: C8H20N2O3
  • MW: 192.256
  • Catalog: PROTAC Linker
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 291.1±25.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 131.8±16.8 °C

Thalidomide-O-amido-PEG4-azide

Thalidomide-O-amido-PEG4-azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2411681-89-3
  • MF: C25H32N6O10
  • MW: 576.56
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3,4-Dibromo-Mal-PEG2-amine TFA

3,4-Dibromo-Mal-PEG2-amine TFA is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2296708-07-9
  • MF: C12H15Br2F3N2O6
  • MW: 500.06
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mal-Amido-PEG4-Boc

Mal-Amido-PEG4-Boc is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1415800-35-9
  • MF: C22H36N2O9
  • MW: 472.529
  • Catalog: PROTAC Linker
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 626.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 332.6±31.5 °C