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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PROTAC ER Degrader-10

PROTAC ER Degrader-10 is a potent PROTAC ER degrader and can be used for cancer research. PROTAC ER Degrader-10 is extracted from patent WO2021133886, example 36.

  • CAS Number: 2504911-58-2
  • MF: C44H45N5O6
  • MW: 739.86
  • Catalog: PROTAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tosylate of Tetraethylene glycol monobenzyl ether

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

  • CAS Number: 89346-82-7
  • MF: C22H32O8S
  • MW: 456.55000
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC AR-V7 degrader-2

PROTAC AR-V7 degrader-2 is an AR-based PROTAC. PROTAC AR-V7 degrader-2 inhibits CaP cellular proliferation by degrading AR-V7 and AR-FL. PROTAC AR-V7 degrader-2 induces apoptosis[1].

  • CAS Number: 2488296-74-6
  • MF: C43H53F2N7O7S2
  • MW: 882.05
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VH 032 amide-PEG2-amine

(S,R,S)-AHPC-PEG2-NH2 dihydrochloride (VH032-PEG2-NH2 dihydrochloride) is a synthesized E3 ligase ligand-linker conjugate that incorporates the (S,R,S)-AHPC based VHL ligand and 2-unit PEG linker used in the synthesis of PROTACs[1].

  • CAS Number: 2341796-76-5
  • MF: C28H43Cl2N5O6S
  • MW: 648.64
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TBK1 PROTAC 1

A novel potent, selective TBK1 PROTAC with DC50 of 12 nM, selectively degrades TBK1 with excellent selectivity against a related kinase IKKε; a chemical tool to assess TBK1 as a target in mutant K-Ras cancer cells.

  • CAS Number: 2052306-13-3
  • MF: C53H74BrN9O9S
  • MW: 1093.179
  • Catalog: IKK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Propargyl-PEG1-acid

Propargyl-PEG1-acid is a PEG-based PROTAC linker can be used in the synthesis of BTK-CRBN PROTACs Ibrutinib(HY-10997)-based PROTAC 4 and PROTAC 5. PROTAC 5 causes the degradation of BTK and induces the degradation of CSK, LYN, and LAT2 at 10 μM[1].

  • CAS Number: 55683-37-9
  • MF: C6H8O3
  • MW: 128.12600
  • Catalog: PROTAC Linker
  • Density: 1.14g/cm3
  • Boiling Point: 265.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 113.9ºC

Thalidomide-Piperazine-PEG3-NH2

Thalidomide-Piperazine-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: 2357113-68-7
  • MF: C25H35N5O7
  • MW: 517.57
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bis-PEG4-TFP ester

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

  • CAS Number: 1446282-42-3
  • MF: C24H22F8O8
  • MW: 590.414
  • Catalog: PROTAC Linker
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 572.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 289.0±25.0 °C

Thalidomide-O-C6-NH2

Thalidomide-O-C6-NH2 is a synthesized E3 ligase ligand-linker conjugate used in the PROTAC dTAG-13, a degrader of FKBP12F36V and BET[1].

  • CAS Number: 1957235-98-1
  • MF: C19H23N3O5
  • MW: 373.40
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC EGFR degrader 6

PROTAC EGFR degrader 6 (Compound 2), a PROTAC EGFR degrader, potently degrades EGFRDel19 in HCC827 cells with the DC50 of 45.2 nM. PROTAC EGFR degrader 6 significantly induces the apoptosis of HCC827 cells and arrest the cells in G1 phase[1].

  • CAS Number: 2409793-28-6
  • MF: C49H57FN12O5
  • MW: 913.05
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-(PEG1-OH)-N-Boc-PEG2-propargyl

N-(PEG1-OH)-N-Boc-PEG2-propargyl is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2100306-85-0
  • MF: C16H29NO6
  • MW: 331.40
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aminooxy-PEG3-propargyl

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

  • CAS Number: 1807537-27-4
  • MF: C9H17NO4
  • MW: 203.236
  • Catalog: PROTAC Linker
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 309.6±32.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 146.4±18.8 °C

S-acetyl-PEG6

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

  • CAS Number: 1352221-63-6
  • MF: C14H28O7S
  • MW: 340.433
  • Catalog: PROTAC Linker
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 441.7±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 220.9±28.7 °C

Boc-NH-C6-amido-C4-acid

PROTAC Linker 32 is a PROTAC linker, which refers to the alkyl/ether composition. PROTAC Linker 32 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: 10436-21-2
  • MF: C17H32N2O5
  • MW: 344.45
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azido-PEG6-MS

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

  • CAS Number: 352439-38-4
  • MF: C13H27N3O8S
  • MW: 385.43
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bromo-PEG3-azide

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

  • CAS Number: 1446282-43-4
  • MF: C8H16BrN3O3
  • MW: 282.135
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FKBP12 PROTAC RC32

FKBP12 PROTAC RC32 (RC32) is a potent FKBP12 degrader based on PROTAC technology. FKBP12 PROTAC RC32 contains conjugation of Rapamycin (HY-10219) and a ligand for an E3 ubiquitin ligase (Pomalidomide; HY-10984)[1].

  • CAS Number: 2375555-66-9
  • MF: C75H107N7O20
  • MW: 1426.69
  • Catalog: PROTAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Amino-PEG4-Boc

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

  • CAS Number: 581065-95-4
  • MF: C15H31NO6
  • MW: 321.41000
  • Catalog: PROTAC Linker
  • Density: 1.040±0.06 g/cm3
  • Boiling Point: 400.1±35.0 ºC (760 Torr)
  • Melting Point: N/A
  • Flash Point: 114.1±22.3 ºC

(S,R,S)-AHPC-C6-NH2 dihydrochloride

(S,R,S)-AHPC-C6-NH2 dihydrochloride (VH032-C6-NH2 dihydrochloride) 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-C6-NH2 dihydrochloride is XF038-161A, example 6, extracted from patent WO2019173516A1[1].

  • CAS Number: 2341796-77-6
  • MF: C29H45Cl2N5O4S
  • MW: 630.67
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azido-PEG3-Val-Cit-PAB-PNP

Azido-PEG3-Val-Cit-PAB-PNP is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1]. Azido-PEG3-Val-Cit-PAB-PNP is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[2].

  • CAS Number: 2055047-18-0
  • MF: C34H47N9O12
  • MW: 773.79
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

11-Aminoundecanoic acid

11-Aminoundecanoic acid is a PROTAC linker, which refers to the alkyl chain composition. 11-Aminoundecanoic acid can be used in the synthesis of a series of PROTACs.

  • CAS Number: 2432-99-7
  • MF: C11H23NO2
  • MW: 201.306
  • Catalog: PROTAC Linker
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 334.9±15.0 °C at 760 mmHg
  • Melting Point: 188-191 °C(lit.)
  • Flash Point: 156.3±20.4 °C

Bromo-PEG2-MS

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

  • CAS Number: 1935075-34-5
  • MF: C5H11BrO4S
  • MW: 247.11
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Thalidomide-4-O-CH2-COO(t-Bu)

Thalidomide-4-O-CH2-COO(t-Bu) is t-Bu modified Thalidomide (HY-14658), which is the final step intermediate in the synthesis of Thalidomide-4-OH (HY-123096). Thalidomide-4-O-CH2-COO(t-Bu) acts as a Cereblon ligand to recruit CRBN proteins. The t-Bu protecting group at the end of Thalidomide-4-O-CH2-COO(t-Bu) can be removed under acidic conditions to participate in the synthesis of PROTAC molecules. Thalidomide-4-O-CH2-COO(t-Bu) is a key intermediate in the synthesis of CRBN-based designed PROTAC molecules.

  • CAS Number: 1950635-36-5
  • MF: C19H20N2O7
  • MW: 388.37
  • Catalog: Ligand for E3 Ligase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Biotin-PEG4-amide-Alkyne

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

  • CAS Number: 1006592-45-5
  • MF: C24H40N4O7S
  • MW: 528.662
  • Catalog: PROTAC Linker
  • Density: 1.174
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N33-TEG-COOH

N33-TEG-COOH is a PROTAC linker containing four polyethylene glycol (PEG) units.

  • CAS Number: 201467-81-4
  • MF: C10H19N3O6
  • MW: 277.27400
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Methylamino-PEG3-t-butyl ester

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

  • CAS Number: 217817-03-3
  • MF: C14H29NO5
  • MW: 291.38
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1,1,1-Trifluoroethyl-PEG3-Propargyl

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

  • CAS Number: 1835759-73-3
  • MF: C9H13F3O3
  • MW: 226.19
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HJM-561

HJM-561 is a potent, selective, orally bioavailable EGFR PROTAC. HJM-561 overcomes osimertinib (HY-15772)-resistant EGFR triple mutations and has anti-tumor activity[1].

  • CAS Number: 2570251-68-0
  • MF: C45H51ClN9O5P
  • MW: 864.37
  • Catalog: PROTAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hydroxy-PEG2-CH2COOH

Hydroxy-PEG2-CH2COOH is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 51951-04-3
  • MF: C6H12O5
  • MW: 164.156
  • Catalog: PROTAC Linker
  • Density: 1.2±0.0 g/cm3
  • Boiling Point: 343.4±0.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 144.3±0.0 °C

m-PEG12-NH-C2-acid

m-PEG12-NH-C2-acid is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1949843-39-3
  • MF: C28H57NO14
  • MW: 631.75
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A