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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tans-4-Hydroxy-D-proline methyl ester hydrochloride

tans-4-Hydroxy-D-proline methyl ester hydrochloride is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). tans-4-Hydroxy-D-proline methyl ester hydrochloride is also a alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[1][2].

  • CAS Number: 481704-21-6
  • MF: C6H12ClNO3
  • MW: 181.617
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AU-15330

AU-15330 is a proteolysis-targeting chimera (PROTAC) degrader of the SWI/SNF ATPase subunits, SMARCA2 and SMARCA4. AU-15330 induces potent inhibition of tumour growth in xenograft models of prostate cancer and synergizes with the AR antagonist enzalutamide. AU-15330 induces disease remission in castration-resistant prostate cancer (CRPC) models without toxicity[1].

  • CAS Number: 2380274-50-8
  • MF: C39H49N9O5S
  • MW: 755.93
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tetraethylene glycol monomethyl ether

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

  • CAS Number: 23783-42-8
  • MF: C9H20O5
  • MW: 208.252
  • Catalog: PROTAC Linker
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 285.4±25.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 126.4±23.2 °C

3,6,9-Trioxaundecanedioic acid

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

  • CAS Number: 13887-98-4
  • MF: C8H14O7
  • MW: 222.193
  • Catalog: PROTAC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 443.7±30.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 178.3±18.1 °C

Lenalidomide-d5

Lenalidomide-d5 is deuterium labeled Lenalidomide. Lenalidomide (CC-5013), a derivative of Thalidomide, acts as molecular glue. Lenalidomide is an orally active immunomodulator. Lenalidomide (CC-5013) is a ligand of ubiquitin E3 ligase cereblon (CRBN), and it causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. Lenalidomide (CC-5013) specifically inhibits growth of mature B-cell lymphomas, including multiple myeloma, and induces IL-2 release from T cells[1][2].

  • CAS Number: 1227162-34-6
  • MF: C13H8D5N3O3
  • MW: 264.29
  • Catalog: Apoptosis
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 614.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 325.1±31.5 °C

CRBN-6-5-5-VHL

CRBN-6-5-5-VHL is a potent and selective cereblon (CRBN) degrader with a DC50 value of 1.5 nM. CRBN-6-5-5-VHL has almost no effect on the degradation of the neo-substrates IKZF1 and IKZF3[1].

  • CAS Number: 2362575-45-7
  • MF: C51H69N7O10S
  • MW: 972.20
  • Catalog: PROTAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Methylamino-PEG2-Boc

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

  • CAS Number: 1807521-04-5
  • MF: C12H25NO4
  • MW: 247.331
  • Catalog: PROTAC Linker
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 315.5±22.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 144.6±22.3 °C

NH-bis(PEG2-t-butyl ester)

NH-bis(PEG2-C2-Boc) is an alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1964503-36-3
  • MF: C22H43NO8
  • MW: 449.58
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG3-OH

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

  • CAS Number: 112-35-6
  • MF: C7H16O4
  • MW: 164.199
  • Catalog: PROTAC Linker
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 233.9±20.0 °C at 760 mmHg
  • Melting Point: -44ºC
  • Flash Point: 95.3±21.8 °C

TCO4-PEG2-Maleimide

TCO4-PEG2-Maleimide is a PROTAC linker and belongs to the PEG class. TCO4-PEG2-Maleimide contains TCO and Maleimide groups, which can undergo specific "click" reactions with tetrazine groups or thiol groups, or "mercapto-acrylamide" reactions.

  • CAS Number: 2141981-85-1
  • MF: C22H33N3O7
  • MW: 451.51
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BocNH-PEG5-CH2CH2Br

BocNH-PEG5-CH2CH2Br is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1392499-33-0
  • MF: C17H34BrNO7
  • MW: 444.36
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S,R,S)-AHPC-Boc-trans-3-aminocyclobutanol-Pip-CH2COOH

(S,R,S)-AHPC-Boc-trans-3-aminocyclobutanol-Pip-CH2COOH (VH032-Boc-trans-3-aminocyclobutanol-Pip-CH2COOH) is a E3 ligase ligand-linker conjugate that contains on one end a VHL ligand. (S,R,S)-AHPC-Boc-trans-3-aminocyclobutanol-Pip-CH2COOH is used in PROTAC technology[1].

  • CAS Number: 2086301-47-3
  • MF: C39H58N6O7S
  • MW: 754.98
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azido-PEG2-C6-Cl

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

  • CAS Number: 2568146-55-2
  • MF: C10H20ClN3O2
  • MW: 249.74
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Amino-Tri-(m-PEG4-ethoxymethyl)-methane

Amino-Tri-(m-PEG4-ethoxymethyl)-methane is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1428661-67-9
  • MF: C40H80N4O18
  • MW: 905.08
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BSJ-03-204

BSJ-03-204 is a potent and selective Palbociclib-based CDK4/6 dual degrader (PROTAC), with IC50s of 26.9 nM and 10.4 nM for CDK4/D1 and CDK6/D1, respectively. BSJ-03-204 does not induce IKZF1/3 degradation and has anti-cancer activity[1].

  • CAS Number: 2349356-09-6
  • MF: C43H48N10O8
  • MW: 832.90
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azido-PEG5-S-methyl ethanethioate

Azido-PEG5-S-methyl ethanethioate is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1352221-64-7
  • MF: C14H27N3O6S
  • MW: 365.45
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bromo-PEG5-azide

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

  • CAS Number: 1402411-90-8
  • MF: C12H24BrN3O5
  • MW: 370.24
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SIAIS178

SIAIS178 is a potent and selective BCR-ABL degrader based on PROTAC technology with an IC50 of 24 nM. SIAIS178 causes effective degradation of BCR-ABL protein by recruiting Von Hippel-Lindau (VHL) E3 ubiquitin ligase. SIAIS178 has anticancer activity[1].

  • CAS Number: 2376047-73-1
  • MF: C50H62ClN11O6S2
  • MW: 1012.68
  • Catalog: PROTAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Amino-PEG9-alcohol

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

  • CAS Number: 15332-95-3
  • MF: C18H39NO9
  • MW: 413.50
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Mal-N-bis(PEG4-NH-Boc)

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

  • CAS Number: 2128735-27-1
  • MF: C37H66N4O15
  • MW: 806.94
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Biotin-PEG8-alcohol

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

  • CAS Number: 2182601-20-1
  • MF: C26H49N3O10S
  • MW: 595.75
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tetraethylene Glycol Monobenzyl Ether

BnO-PEG4-OH is a PEG-based PROTAC linker can be used in the synthesis of PROTACs.

  • CAS Number: 86259-87-2
  • MF: C15H24O5
  • MW: 284.348
  • Catalog: PROTAC Linker
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 398.7±32.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 194.9±25.1 °C

NH2-C2-amido-C2-Boc

NH2-C2-amido-C2-Boc is a PROTAC linker, which refers to the alkyl/ether composition. NH2-C5-NH-Boc can be used in the synthesis of a series of PROTACs, such as the PROTAC CDK2/9 Degrader-1 (HY-130709)[1].

  • CAS Number: 1692613-62-9
  • MF: C10H20N2O3
  • MW: 216.28
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

THP-PEG4-OH

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

  • CAS Number: 128660-97-9
  • MF: C13H26O6
  • MW: 278.342
  • Catalog: PROTAC Linker
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 394.0±42.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 192.1±27.9 °C

Hydroxy-PEG5-C2-methyl ester

Hydroxy-PEG5-C2-methyl ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2100306-80-5
  • MF: C14H28O8
  • MW: 440.53
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

t-Boc-Aminooxy-PEG3-alcohol

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

  • CAS Number: 252378-66-8
  • MF: C11H23NO6
  • MW: 265.303
  • Catalog: PROTAC Linker
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tetrazine-Ph-PEG5-NHS ester

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

  • CAS Number: 1682653-80-0
  • MF: C27H36N6O10
  • MW: 604.609
  • Catalog: PROTAC Linker
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Thalidomide-NH-PEG2-C2-NH-Boc

Thalidomide-NH-PEG2-C2-NH-Boc is a synthesized E3 ligase ligand-linker conjugate that incorporates the Thalidomide based cereblon ligand and a PEG linker used for dBRD9 (compound 6) synthesis. dBRD9 is a selective BRD9 probe PROTAC degrader for the study of BAF complex biology[1].

  • CAS Number: 2097509-40-3
  • MF: C24H32N4O8
  • MW: 504.53
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Docosanedioic acid

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

  • CAS Number: 505-56-6
  • MF: C22H42O4
  • MW: 370.566
  • Catalog: ADC Linker
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 527.0±23.0 °C at 760 mmHg
  • Melting Point: 72-80 °C(lit.)
  • Flash Point: 286.6±19.1 °C

Aminooxy-PEG8-acid

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

  • CAS Number: 2055013-68-6
  • MF: C19H39NO11
  • MW: 457.51
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A