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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Propanol-PEG3-CH2OH

Propanol-PEG3-CH2OH is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 112935-57-6
  • MF: C10H22O5
  • MW: 222.28
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Thalidomide-benzo

Thalidomide-benzo hydrochloride is the Thalidomide-based cereblon ligand used in the recruitment of CRBN protein. Thalidomide-benzo can be connected to the ligand for protein by a linker to form PROTACs[1].

  • CAS Number: 458151-34-3
  • MF: C17H12N2O4
  • MW: 308.29
  • Catalog: Ligand for E3 Ligase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

t-Butyl acetate-PEG2-CH2COOH

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

  • CAS Number: 883564-93-0
  • MF: C12H22O7
  • MW: 278.30
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC FLT-3 degrader 1

PROTAC FLT-3 degrader 1 is an FLT-3 internal tandem duplication (ITD) degrader with an IC50 0.6 nM. Anti-proliferative activity; apoptosis induction[1].

  • CAS Number: 2230826-81-8
  • MF: C52H61N9O9S2
  • MW: 1020.23
  • Catalog: PROTAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azide-PEG5-Boc

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

  • CAS Number: 1415800-41-7
  • MF: C17H33N3O7
  • MW: 391.460
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ERK-CLIPTAC

ERK-CLIPTAC is a PROTAC molecule that triggers the degradation of ERK[1].

  • CAS Number: 2087490-46-6
  • MF: C60H61ClN12O9
  • MW: 1129.65
  • Catalog: PROTAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC EED degrader-1

PROTAC EED degrader-1 is a PROTAC targeting EED with a pKD of 9.02. PROTAC EED degrader-1 is a polycomb repressive complex 2 (PRC2) inhibitor (pIC50=8.17) targeting the EED subunit[1].

  • CAS Number: 2639882-72-5
  • MF: C55H60FN11O8S
  • MW: 1054.20
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC 6

PROTAC CDK9 Degrader-1 is a selective CDK9 degrader.

  • CAS Number: 2118356-96-8
  • MF: C33H35N5O7
  • MW: 613.66
  • Catalog: PROTAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Thalidomide-O-C8-NH2 hydrochloride

Thalidomide-O-C8-NH2 hydrochloride 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: 2636798-38-2
  • MF: C21H28ClN3O5
  • MW: 437.92
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

t-Boc-Aminooxy-PEG1-amine

Boc-Aminooxy-PEG1-C2-NH2 is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1844894-82-1
  • MF: C9H20N2O4
  • MW: 220.27
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG3-Ms

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

  • CAS Number: 60696-83-5
  • MF: C6H14O5S
  • MW: 198.24
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-(Biotin-peg4)-n-bis(peg4-t-butyl ester)

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

  • CAS Number: 2112730-79-5
  • MF: C50H94N4O18S
  • MW: 1071.36
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bromo-PEG3-C2-phosphonic acid

Bromo-PEG3-C2-phosphonic acid is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 1148026-99-6
  • MF: C8H18BrO6P
  • MW: 321.103
  • Catalog: PROTAC Linker
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 458.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 230.9±31.5 °C

Thalidomide-5-O-C2-NH2 hydrochloride

Thalidomide-5-O-C2-NH2 hydrochloride is the Thalidomide (HY-10984)-based cereblon ligand used in the recruitment of CRBN protein.Thalidomide-5-O-C2-NH2 hydrochloride can be connected to the ligand for protein by a linker to form PROTACs[1].

  • CAS Number: 2694727-89-2
  • MF: C15H16ClN3O5
  • MW: 353.76
  • Catalog: Ligand for E3 Ligase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-tert-Butoxycarbonyl-trans-4-hydroxy-D-proline

N-tert-Butoxycarbonyl-trans-4-hydroxy-D-proline is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). N-tert-Butoxycarbonyl-trans-4-hydroxy-D-proline is also a alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[1][2].

  • CAS Number: 147266-92-0
  • MF: C10H17NO5
  • MW: 231.246
  • Catalog: ADC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 390.9±42.0 °C at 760 mmHg
  • Melting Point: 123ºC
  • Flash Point: 190.2±27.9 °C

Benzyl-PEG3-methyl ester

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

  • CAS Number: 127457-61-8
  • MF: C15H22O5
  • MW: 282.33
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Biotin-C5-NHS Ester

Biotin-C5-NHS Ester is an alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 72040-63-2
  • MF: C20H30N4O6S
  • MW: 454.540
  • Catalog: PROTAC Linker
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 169-171 °C
  • Flash Point: N/A

PROTAC Linker 9

PROTAC Linker 9 is a PROTAC linker, which refers to the alkyl/ether composition. PROTAC Linker 9 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: 206265-94-3
  • MF: C18H29NO7S
  • MW: 403.49000
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ERD-3111

ERD-3111 (Compound 44) is an orally active PROTAC ERα degrader (DC50: 0.5 nM). ERD-3111 inhibits tumor growth in the parental MCF-7 xenograft model with wild-type ER and two clinically relevant ESR1 mutated mice model. ERD-3111 can be used in the research of ER+ breast cancer[1].

  • CAS Number: 2832865-25-3
  • MF: C45H46F4N8O5
  • MW: 854.89
  • Catalog: PROTAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S,R,S)-AHPC-C7-amine

(S,R,S)-AHPC-C7-amine (VH032-C7-amine) is a synthesized E3 ligase ligand-linker conjugate that incorporates the VH032 based VHL ligand and a linker used for estrogen-related receptor α (ERRα) PROTAC degrader[1].

  • CAS Number: 2306389-04-6
  • MF: C30H45N5O4S
  • MW: 571.77
  • Catalog: E3 Ligase Ligand-Linker Conjugate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azidoethyl-PEG2-t-Butyl ester

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

  • CAS Number: 2144777-83-1
  • MF: C13H25N3O4S2
  • MW: 351.49
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Propargyl-PEG8-SH

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

  • CAS Number: 1422540-92-8
  • MF: C19H36O8S
  • MW: 424.55
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-methyl-N'-methyl-O-(m-PEG4)-O'-(propargyl-PEG4)-Cy5

N-methyl-N'-methyl-O-(m-PEG4)-O'-(propargyl-PEG4)-Cy5 is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2107273-50-5
  • MF: C47H67ClN2O10
  • MW: 855.50
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Benzyl-PEG6-bromide

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

  • CAS Number: 1449202-44-1
  • MF: C19H31BrO6
  • MW: 435.35
  • Catalog: PROTAC Linker
  • Density: 1.225±0.06 g/cm3(Predicted)
  • Boiling Point: 481.4±40.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

L-Azidohomoalanine

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

  • CAS Number: 120042-14-0
  • MF: C4H8N4O2
  • MW: 144.13200
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 220-223ºC
  • Flash Point: N/A

TNF-α-IN-1

TNF-α-IN-1 is a TNF-α inhibitor extracted from patent US20030096841A1, compound example I-7.

  • CAS Number: 444287-49-4
  • MF: C16H14ClN3O5
  • MW: 363.753
  • Catalog: Ligand for E3 Ligase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 718.6±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 388.4±32.9 °C

m-PEG6-(CH2)8-phosphonic acid

m-PEG6-(CH2)6-Phosphonic acid is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 2028284-71-9
  • MF: C19H41O9P
  • MW: 444.50
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aeide-C1-NHS ester

Aeide-C1-NHS ester is an alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 824426-32-6
  • MF: C6H6N4O4
  • MW: 198.13600
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CC-885-CH2-PEG1-NH-CH3

CC-885-CH2-PEG1-NH-CH3 is a neoDegrader that can be used in the synthesis of Antibody neoDegrader Conjugate (AnDC)[1][2].

  • CAS Number: 2722698-03-3
  • MF: C26H30ClN5O5
  • MW: 528.00
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tetrazine-Acid

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

  • CAS Number: 1380500-92-4
  • MF: C10H8N4O2
  • MW: 216.20
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A