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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Boc-NH-PEG2-NH-Boc

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

  • CAS Number: 475591-59-4
  • MF: C16H32N2O6
  • MW: 348.43500
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bis-propargyl-PEG1

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

  • CAS Number: 40842-04-4
  • MF: C8H10O2
  • MW: 138.16400
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

t-Boc-Aminooxy-PEG2-amine

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

  • CAS Number: 252378-69-1
  • MF: C11H24N2O5
  • MW: 264.32
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pomalidomide 4'-PEG3-azide

Pomalidomide 4'-PEG3-azide is a synthesized E3 ligase ligand-linker conjugate that incorporates the Pomalidomide-based cereblon ligand and a linker. Pomalidomide 4'-PEG3-azide can be used for the synthesis of iRucaparib-TP3 (Compound 3). iRucaparib-TP3 is a highly efficient PARP1 degrader based on Rucaparib by using the PROTAC approach[1].

  • CAS Number: 2271036-46-3
  • MF: C21H26N6O7
  • MW: 474.47
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lenalidomide-4-aminomethyl

Lenalidomide-4-aminomethyl is the Lenalidomide-based cereblon (CRBN) ligand used in the recruitment of CRBN protein. Lenalidomide-4-aminomethyl can be connected to the ligand for protein by a linker to form PROTAC[1].

  • CAS Number: 790652-68-5
  • MF: C14H15N3O3
  • MW: 273.29
  • Catalog: Ligand for E3 Ligase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azido-PEG6-acid

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

  • CAS Number: 361189-66-4
  • MF: C15H29N3O8
  • MW: 379.41
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mz1

MZ 1 is a BRD4 protein degrader based on PROTAC technology.

  • CAS Number: 1797406-69-9
  • MF: C49H60ClN9O8S2
  • MW: 1002.64
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC STAT3 degrader-2

PROTAC STAT3 degrader-2 is a selective and efficacious PROTAC degrader of STAT3 protein with a DC50 of 3.54 μM in Molm-16 Cell. PROTAC STAT3 degrader-2 has the potential for cancer research[1].

  • CAS Number: 2429877-78-9
  • MF: C59H60F2N9O13P
  • MW: 1172.13
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG3-S-PEG4-propargyl

m-PEG3-S-PEG4-propargyl is a PEG-based PROTAC linker can be used in the synthesis of PROTACs[1].

  • CAS Number: 2055040-85-0
  • MF: C18H34O7S
  • MW: 394.52
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bromoacetamido-PEG2-C2-acid

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

  • CAS Number: 1415800-44-0
  • MF: C9H16BrNO5
  • MW: 298.131
  • Catalog: PROTAC Linker
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 491.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 251.0±28.7 °C

Sulfo DBCO-PEG4-Maleimide

Sulfo DBCO-PEG4-Maleimide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2055198-07-5
  • MF: C39H47N5O13S
  • MW: 825.88
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ms-PEG4-t-butyl ester

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

  • CAS Number: 870487-48-2
  • MF: C16H32O9S
  • MW: 400.485
  • Catalog: PROTAC Linker
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 499.9±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 256.1±27.3 °C

SCO-PEG3-COOH

SCO-PEG3-COOH is a PROTAC linker and belongs to the PEG class. SCO-PEG3-COOH contains SCO and COOH that can be covalently combined with amino groups respectively. SCO is often used to react with amino acid residues of proteins or peptides, particularly lysine.

  • CAS Number: 2141976-36-3
  • MF: C18H29NO7
  • MW: 371.43
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Diazo Biotin-PEG3-azide

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

  • CAS Number: 1339202-33-3
  • MF: C33H45N9O7S
  • MW: 711.831
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG7-Tos

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

  • CAS Number: 79622-11-0
  • MF: C22H38O10S
  • MW: 494.59600
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azido-PEG4-tetra-Ac-beta-D-glucose

Azido-PEG4-tetra-Ac-beta-D-glucose is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 153252-44-9
  • MF: C22H35N3O13
  • MW: 549.53
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-(5-(aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

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

  • CAS Number: 1158264-69-7
  • MF: C14H16ClN3O3
  • MW: 309.748
  • Catalog: Ligand for E3 Ligase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DBCO-PEG1-acid

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

  • CAS Number: 2228857-38-1
  • MF: C24H24N2O5
  • MW: 420.46
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC RIPK degrader-2

PROTAC RIPK degrader-2 is a nonpeptidic PROTAC which potently targets serine-threonine kinase RIPK2 and has highly selective for RIPK2 degradation[1].

  • CAS Number: 1801547-16-9
  • MF: C52H65N7O11S3
  • MW: 1060.31
  • Catalog: PROTAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NH2-PEG3-C6-Cl

NH2-PEG3-C6-Cl is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1261350-60-0
  • MF: C12H26ClNO3
  • MW: 267.79
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Me-PEG4-Me

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

  • CAS Number: 143-24-8
  • MF: C10H22O5
  • MW: 222.279
  • Catalog: PROTAC Linker
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 275.3±0.0 °C at 760 mmHg
  • Melting Point: −30 °C(lit.)
  • Flash Point: 140.6±0.0 °C

Ethyl acetate-PEG1

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

  • CAS Number: 2093-20-1
  • MF: C6H12O4
  • MW: 148.15700
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HO-PEG14-OH

HO-PEG14-OH is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1189112-05-7
  • MF: C28H58O15
  • MW: 634.751
  • Catalog: PROTAC Linker
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 660.2±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 353.1±30.1 °C

Ac4GlcNAlk

Ac4GlcNAlk is an alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1361993-37-4
  • MF: C19H25NO10
  • MW: 427.40
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ND1-YL2

ND1-YL2 is a PROTAC that selectively degrades SRC-1 via the N-degron pathway. ND1-YL2 significantly inhibits cancer invasion and migration in vitro and in vivo. ND1-YL2 can be used in cancer research[1].

  • CAS Number: 2582803-80-1
  • MF: C114H189N27O28
  • MW: 2385.88
  • Catalog: PROTAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acryloyl-PEG4-OH

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

  • CAS Number: 26150-06-1
  • MF: C11H22O5
  • MW: 234.28900
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cbl-b-IN-2

Cbl-b-IN-2 (Example 8) is an orally bioavailable compound, can inhibit the E3 enzyme Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b) in the ubiquitin proteasome pathway. Cbl-b-IN-2 can be used to modulate the immune system and diseases amenable to immune system modulation. Cbl-b-IN-2 (Example 8) also may be administered to an individual with cancer, either alone or as part of a combination, with one or more of an immune checkpoint inhibitor, an anti-neoplastic agent, and radiation agent[1].

  • CAS Number: 2503325-21-9
  • MF: C29H30F5N5O2
  • MW: 575.57
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pyrene-PEG2-azide

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

  • CAS Number: 2135330-58-2
  • MF: C23H22N4O3
  • MW: 402.45
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BM-PEG3

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

  • CAS Number: 86099-06-1
  • MF: C16H20N2O7
  • MW: 352.33900
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 71-72ºC
  • Flash Point: N/A

PROTAC RAF degrader 1

PROTAC RAF degrader 1 (compound 512) is a PROTAC RAF degrader. PROTAC RAF degrader 1 induces targeted degradation of BRAF mutants (DC50: 5.4 nM, 4.64 nM, 15.5 nM, 2.11 nM, 63.9 nM for BRAF V600E, V600K, G464V, G469A, K601E respectively). PROTAC RAF degrader 1 has anti-tumor activity. PROTAC RAF degrader 1 can be used for research of disorders that result from aggregation or accumulation of RAF, or the constitutive activation of RAF[1].

  • CAS Number: 2413035-41-1
  • MF: C51H57F2N9O7S2
  • MW: 1010.18
  • Catalog: Raf
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A