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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Fluorescein-thiourea-PEG2-azide

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

  • CAS Number: 1146195-72-3
  • MF: C27H25N5O7S
  • MW: 563.582
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dde Biotin-PEG4-azide

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

  • CAS Number: 1802907-93-2
  • MF: C32H53N7O8S
  • MW: 695.87
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nonaethylene glycol monomethyl ether

Nonaethylene glycol monomethyl ether is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 6048-68-6
  • MF: C19H40O10
  • MW: 428.515
  • Catalog: PROTAC Linker
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 490.1±40.0 °C at 760 mmHg
  • Melting Point: 14ºC
  • Flash Point: 250.2±27.3 °C

Thalidomide-5-NH-PEG2-NH2 hydrochloride

Thalidomide-5-NH-PEG2-NH2 hydrochloride is a Thalidomide (HY-14658)-based cereblon ligand that recruits CRBN proteins. Thalidomide-5-NH-PEG2-NH2 hydrochloride can be connected to the target protein ligand through a linker to form a PROTAC molecule. For example, THAL-SNS-032 (HY-123937).

  • CAS Number: 2357110-58-6
  • MF: C19H25ClN4O6
  • MW: 440.88
  • Catalog: Ligand for E3 Ligase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aminooxy-PEG4-azide

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

  • CAS Number: 2100306-61-2
  • MF: C10H22N4O5
  • MW: 278.31
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bis-PEG6-acid

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

  • CAS Number: 119189-70-7
  • MF: C16H30O10
  • MW: 382.403
  • Catalog: PROTAC Linker
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 543.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 187.7±23.6 °C

Azido-PEG3-S-PEG4-t-butyl ester

Azido-PEG3-S-PEG4-t-butyl ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2055041-19-3
  • MF: C23H45N3O9S
  • MW: 539.68
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Boc-n-bis(peg4-oh)

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

  • CAS Number: 2093154-02-8
  • MF: C25H51NO12
  • MW: 557.67
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

t-Boc-aminooxy-PEG6-propargyl

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

  • CAS Number: 2093152-83-9
  • MF: C20H37NO9
  • MW: 435.51
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MS4077

MS4077 is an anaplastic lymphoma kinase (ALK) PROTAC (degrader) with a Kd of 37 nM for binding affinity to ALK[1].

  • CAS Number: 2230077-10-6
  • MF: C55H72ClN9O13S
  • MW: 1134.73
  • Catalog: PROTAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fluorescein-PEG6-Acid

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

  • CAS Number: 2055014-69-0
  • MF: C36H42N2O13S
  • MW: 742.79
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Benzyl-PEG8-Ms

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

  • CAS Number: 1330059-91-0
  • MF: C24H42O11S
  • MW: 538.65
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MS98

MS98 is a potent and selective PROTAC AKT degrader. MS98 depletes cellular total AKT (T-AKT) with the DC50 value of 78 nM. MS98 binds to AKT1, AKT2, and AKT3 with Kds of 4 nM, 140 nM, and 8.1 nM, respectively[1].

  • CAS Number: 2376137-31-2
  • MF: C58H81ClN10O7S
  • MW: 1097.84
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tos-PEG6-CH2CO2tBu

Tos-PEG5-CH2COOtBu is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1949793-62-7
  • MF: C23H38O10S
  • MW: 506.61
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG8-bromide

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

  • CAS Number: 1056881-04-9
  • MF: C17H35BrO8
  • MW: 447.36
  • Catalog: PROTAC Linker
  • Density: 1.198±0.06 g/cm3(Predicted)
  • Boiling Point: 462.5±40.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

Bis-propargyl-PEG9

Bis-propargyl-PEG9 is a PEG-based PROTAC linker used in the synthesis of PROTACs. Bis-propargyl-PEG9 can be used to synthesize the bivalent estrogen receptor ligands[1].

  • CAS Number: 1351373-47-1
  • MF: C24H42O10
  • MW: 490.584
  • Catalog: PROTAC Linker
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 529.5±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 197.4±28.6 °C

cIAP1 Ligand-Linker Conjugates 12

E3 ligase Ligand-Linker Conjugates 38 incorporates a cIAP ligand for the E3 ubiquitin ligase, and a PROTAC linker. E3 ligase Ligand-Linker Conjugates 38 can be used to design PROTAC degrader[1].

  • CAS Number: 2095244-52-1
  • MF: C46H64N4O12S2
  • MW: 929.15
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fmoc-PEG5-NHS ester

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

  • CAS Number: 1402080-11-8
  • MF: C32H40N2O11
  • MW: 628.67
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azide-PEG3-Desthiobiotin

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

  • CAS Number: 1426828-06-9
  • MF: C18H34N6O5
  • MW: 414.51
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG3-aldehyde

m-PEG3-aldehyde is a PEG-based PROTAC linker can be used in the synthesis of PROTACs.

  • CAS Number: 356066-46-1
  • MF: C8H16O4
  • MW: 176.21000
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azido-PEG11-amine

Azido-PEG11-amine is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1800414-71-4
  • MF: C24H50N4O11
  • MW: 570.674
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mal-PEG2-NHS

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

  • CAS Number: 329364-72-9
  • MF: C14H16N2O8
  • MW: 340.29
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Iodoacetamide-PEG3-azide

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

  • CAS Number: 1594986-04-5
  • MF: C10H19IN4O4
  • MW: 386.19
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GBD-9

GBD-9 is a double-mechanism degrader that efficiently degrades BTK and GSPT1 by recruiting the E3 ligase cereblon (CRBN). GBD-9 acts both as a PROTAC molecule to induce the degradation of BTK and as a molecular glue to degrade GSPT1. GBD-9 effectively inhibits cancer cell growth[1].

  • CAS Number: 2864408-92-2
  • MF: C44H47N9O6
  • MW: 797.90
  • Catalog: PROTAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

t-Boc-Aminooxy-PEG4-azide

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

  • CAS Number: 2100306-64-5
  • MF: C15H30N4O7
  • MW: 378.42
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AEEA-AEEA

AEEA-AEEA is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). AEEA-AEEA is also a alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[1][2].

  • CAS Number: 1143516-05-5
  • MF: C12H24N2O7
  • MW: 308.32800
  • Catalog: ADC Linker
  • Density: 1.202±0.06 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bis-propargyl-PEG8

Bis-propargyl-PEG7 is a PEG-based PROTAC linker used in the synthesis of PROTACs. Bis-propargyl-PEG7 can be used to synthesize the polymer linked multimers of guanosine-3', 5'-cyclic monophosphates[1].

  • CAS Number: 1351373-46-0
  • MF: C20H34O8
  • MW: 402.48
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6-chlorohexyl bromide

1-Bromo-6-chlorohexane is a PROTAC linker can be used in the synthesis of PROTACs.

  • CAS Number: 6294-17-3
  • MF: C6H12BrCl
  • MW: 199.52
  • Catalog: PROTAC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 217.4±8.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 101.1±0.0 °C

2-((Azido-PEG8-carbamoyl)methoxy)acetic acid

2-((Azido-PEG8-carbamoyl)methoxy)acetic acid is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 846549-37-9
  • MF: C22H42N4O12
  • MW: 554.58800
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pomalidomide-PEG2-azide

Pomalidomide-PEG2-azide is a synthesized E3 ligase ligand-linker conjugate that incorporates the Pomalidomide based cereblon ligand and 2-unit PEG linker used in PROTAC technology[1].

  • CAS Number: 2267306-14-7
  • MF: C19H20N6O7
  • MW: 444.40
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A