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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Pomalidomide-5-C10-NH2 hydrochloride

Pomalidomide-5-C10-NH2 hydrochloride is the Pomalidomide-based cereblon (CRBN) ligand used in the recruitment of CRBN protein.Pomalidomide-5-C10-NH2 hydrochloride can be connected to the ligand for protein by a linker to form PROTAC[1].

  • CAS Number: 2863635-00-9
  • MF: C23H33ClN4O4
  • MW: 464.99
  • Catalog: Ligand for E3 Ligase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Biotin-PEG11-Mal

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

  • CAS Number: 1646619-56-8
  • MF: C41H71N5O16S
  • MW: 922.09
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VH032-C2-NH-Boc

VH032-C2-NH-Boc is a Boc-modified VH032 (HY-120217) that acts as a ligand for VHL and recruits von Hippel-Lindau (VHL) proteins. VH032-C2-NH-Boc will remove the protecting group under acidic conditions, and can be directly used for the synthesis of PROTAC molecules. VH032-C2-NH-Boc is a key intermediate for the synthesis of PROTACs based on VHL ligands.

  • CAS Number: 2361119-87-9
  • MF: C31H45N5O6S
  • MW: 615.78
  • Catalog: Ligand for E3 Ligase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ms-PEG6-Ms

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

  • CAS Number: 109789-40-4
  • MF: C14H34O13S2
  • MW: 474.54200
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

A 410099.1 amide-PEG2-amine-Boc

A 410099.1 amide-PEG2-amine-Boc is a functionalized IAP ligand for PROTACs that incorporates an IAP ligand and an amide-PEG3 linker with terminal amine. A 410099.1 amide-PEG2-amine-Boc can conjugates with target protein ligands.

  • CAS Number: 2415256-16-3
  • MF: C38H60N6O8
  • MW: 728.92
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ARV-825

ARV-825 is a BRD4 Inhibitor based on PROTAC technology. ARV-825 binds to BD1 and BD2 of BRD4 with Kds of 90 and 28 nM, respectively.

  • CAS Number: 1818885-28-7
  • MF: C46H47ClN8O9S
  • MW: 923.432
  • Catalog: Epigenetic Reader Domain
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-(4-(6-Methyl-1,2,4,5-tetrazin-3-yl)phenoxy)-N-(3-(triethoxysilyl)propyl)-3,6,9,12-tetraoxapentadecan-15-amide

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

  • CAS Number: 2353410-01-0
  • MF: C29H49N5O9Si
  • MW: 639.81
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TCO-PNB ester

TCO-PNB ester is an alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1438415-89-4
  • MF: C15H17NO5
  • MW: 291.30
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SLc-nhs-(+)-biotin

Biotin-C10-NHS Ester is an alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 887628-40-2
  • MF: C25H40N4O6S
  • MW: 524.67
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

endo-Bicyclo[6.1.0]non-4-yn-9-ylmethyl (15-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-13-oxo-3,6,9-trioxa-12-azapentadecyl)carbamate

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

  • CAS Number: 2141976-33-0
  • MF: C26H37N3O8
  • MW: 519.59
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Mal-N-bis(PEG4-NHS ester)

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

  • CAS Number: 2112738-60-8
  • MF: C37H54N4O19
  • MW: 858.84
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Desthiobiotin-N-bis(PEG4-t-butyl ester)

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

  • CAS Number: 2353409-60-4
  • MF: C40H75N3O14
  • MW: 822.04
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Chloroacetamido-PEG4-C2-Boc

Chloroacetamido-PEG4-C2-Boc is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs.

  • CAS Number: 1365655-90-8
  • MF: C17H32ClNO7
  • MW: 397.892
  • Catalog: PROTAC Linker
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 527.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 272.9±30.1 °C

PEG3-bis(phosphonic acid)

PEG3-bis(phosphonic acid) is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 254762-10-2
  • MF: C8H20O9P2
  • MW: 322.186
  • Catalog: PROTAC Linker
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 588.2±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 309.5±32.9 °C

1-isothiocyanato-PEG4-Alcohol

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

  • CAS Number: 1835759-69-7
  • MF: C9H17NO4S
  • MW: 235.30
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Benzyl-PEG24-MS

Benzyl-PEG24-MS is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2218463-20-6
  • MF: C56H106O27S
  • MW: 1243.49
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NH2-PEG7

NH2-PEG7 is a PROTAC linker, which refers to the PEG composition. NH2-PEG7 can be used in the synthesis of the PROTAC PARP1 degrader iRucaparib-AP6[1].

  • CAS Number: 1425973-14-3
  • MF: C14H31NO7
  • MW: 325.398
  • Catalog: PROTAC Linker
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 427.3±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 212.2±27.3 °C

PROTAC IRAK4 ligand-3

PROTAC IRAK4 ligand-3 is a ligand of PROTAC IRAK4 degrader-7 (HY-145483). PROTAC IRAK4 ligand-3 can be used for the research of cancer[1].

  • CAS Number: 2434848-46-9
  • MF: C23H25F2N7O3
  • MW: 485.49
  • Catalog: PROTAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VH032 analogue-2

VH032 analogue-2 is a VH032 (HY-120217) analog that acts as a ligand for VHL, recruiting von Hippel-Lindau (VHL) protein. VH032 analogue-2 will remove the protective group under acidic conditions, and can be directly used for the synthesis of PROTAC molecules. VH032 analogue-2 is a key intermediate for the synthesis of PROTACs based on VHL ligands.

  • CAS Number: 1448189-66-9
  • MF: C26H36N4O5S
  • MW: 516.65
  • Catalog: Ligand for E3 Ligase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Methyltetrazine-PEG4-azide

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

  • CAS Number: 1802908-04-8
  • MF: C17H23N7O4
  • MW: 389.41
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SJFδ

SJFδ is a 10-atom linker PROTAC. SJFδ degrades p38α with a DC50 of 46.17 nM, but does not degrade p38α, p38β, or p38γ[1].

  • CAS Number: 2254609-23-7
  • MF: C62H63F2N7O12S
  • MW: 1168.27
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FmocNH-PEG3-CH2CH2NH2 hydrochloride

FmocNH-PEG3-CH2CH2NH2 (hydrochloride) is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 906079-91-2
  • MF: C23H31ClN2O5
  • MW: 450.96
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bis-acrylate-PEG5

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

  • CAS Number: 59256-52-9
  • MF: C16H26O8
  • MW: 346.37300
  • Catalog: PROTAC Linker
  • Density: 1.098g/cm3
  • Boiling Point: 421.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 181.9ºC

S-acetyl-PEG4-propargyl

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

  • CAS Number: 1422540-88-2
  • MF: C13H22O5S
  • MW: 290.37
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ms-PEG8-Ms

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

  • CAS Number: 109789-41-5
  • MF: C16H34O12S2
  • MW: 482.56
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S,R,S)-AHPC-C3-NH2

(S,R,S)-AHPC-C3-NH2 (VH032-C3-NH2) is a synthesized E3 ligase ligand-linker conjugate that incorporates the VH032 based VHL ligand and a linker used in PROTAC technology. (S,R,S)-AHPC-C3-NH2 can be used in the synthesis of a series of PROTACs, such as UNC6852 (HY-130708). UNC6852 is an EED-targeted bivalent chemical degrader[1].

  • CAS Number: 2361119-88-0
  • MF: C26H37N5O4S
  • MW: 515.67
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

E3 ligase Ligand 10

E3 ligase Ligand 10 is a ligand for E3 ubiquitin ligase. E3 ligase Ligand 10 can be connected to the ligand for protein by a linker to form PROTACs or SNIPERs. PROTACs are inducers of ubiquitination-mediated degradation of cancer-promoting proteins[1].

  • CAS Number: 1073560-68-5
  • MF: C47H52N4O7
  • MW: 784.94
  • Catalog: Ligand for E3 Ligase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mal-C4-NH-Boc

Mal-C4-NH-Boc is an alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 124529-64-2
  • MF: C15H24N2O4
  • MW: 296.362
  • Catalog: PROTAC Linker
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 445.8±28.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 223.4±24.0 °C

S-acetyl-PEG6-Tos

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

  • CAS Number: 1818294-25-5
  • MF: C21H34O9S2
  • MW: 494.619
  • Catalog: PROTAC Linker
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 591.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 311.2±30.1 °C

H2N-PEG4-Hydrazide

H2N-PEG4-Hydrazide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1425973-15-4
  • MF: C11H25N3O5
  • MW: 279.33
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A