PROTAC Synthesis

5-Ethynyl-2'-deoxyuridine (EdU), a thymidine analogue, is incorporated into cellular DNA during DNA replication and the subsequent reaction of EdU with a fluorescent azide in a “Click” reaction. EdU staining is a fast, sensitive and reproducible method to study cell proliferation. 5-Ethynyl-2'-deoxyuridine is an alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs. 5-Ethynyl-2'-deoxyuridine is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

DBCO-PEG4-NHS ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. DBCO-PEG4-NHS ester is a click chemistry reagent, it contains a DBCO group that can undergo strain-promoted alkyne-azide cycloaddition (SPAAC) with molecules containing Azide groups.

KT-474 (KYM-001; PROTAC IRAK4 degrader-7) is an orally active PROTAC IRAK4 degrader with anti-tumor effects. KT-474 inhibits the cell cycle and induces apoptosis. KT-474 induces tumor regression in a xenograft model of MYD88-mutated ABC DLBCL.

Biotin-PEG3-azide is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Biotin-PEG3-azide is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.

L-Azidohomoalanine hydrochloride is an alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs. L-Azidohomoalanine (hydrochloride) is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.

(Z)-Sunitinib carboxylic acid is a GSPT1 ligand and can be used for the synthesis of PROTACs, such as MI-389 (HY-136688).

HDAC8 ligand 2 is a HDAC8 ligand that can be used for the synthesis of PROTACs, such as SZUH280 (HY-152147).

N-Desmethyl FN-1501 (Compound 2) is a CDK2/9 ligand that can be used to synthesize PROTACs, such as PROTAC CDK2/9 Degrader-1 (HY-130709).

SD-36 is a potent and efficacious STAT3 PROTAC degrader (K_d=~50 nM), and demonstrates high selectivity over other STAT members. SD-36 also effectively degrades mutated STAT3 proteins in cells and suppresses the transcriptional activity of STAT3 (IC₅₀=10 nM). SD-36 exerts robust anti-tumor activity, and achieves complete and long-lasting tumor regression in mouse tumor models. SD-36 is composed of the STAT3 inhibitor SI-109, a linker, and an analog of Cereblon ligand Lenalidomide for E3 ubiquitin ligase. SD-36 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

Ac4GalNAz is an alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs. Ac4GalNAz is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.

Alkynyl Palmitic Acid (Alk-C16) is an alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs. Alkynyl Palmitic Acid is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

Biotin alkyne is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Biotin alkyne is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

Amino-PEG3-C2-Azido is a PEG-based PROTAC linker can be used in the synthesis of the PARP1 degrader iRucaparib-TP3 (HY-130645). Amino-PEG3-C2-Azido is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.

L-Homopropargylglycine is an alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs. L-homopropargylglycine is an amino acid analog of methionine containing an alkyne moiety that can undergo a classic click chemical reaction with azide containing Alexa Fluor.

Biotin-PEG4-azide is a biotin-labeled, PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Biotin-PEG4-azide is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.

Azido-PEG2-C2-amine (N3-PEG2-CH2CH2NH2) is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG2-C2-amine is also a non-cleavable 2 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG2-C2-amine is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.

Azido-PEG4-NHS-ester is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG4-NHS-ester is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.

AK-2292 is a potent and selective STAT5 PROTAC degrader, with a DC₅₀ of 0.10 μM. AK-2292 induces degradation of STAT5A/B proteins in vitro and in vivo. AK-2292 can induce tumor regression in acute myeloid leukemia and chronic myeloid leukemia xenograft mouse models. AK-2292 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

MD-224 is a first-in-class and highly potent small-molecule human murine double minute 2 (MDM2) degrader based on the proteolysistargeting chimera (PROTAC) concept. MD-224 consists of ligands for Cereblon and MDM2. MD-224 induces rapid degradation of MDM2 at concentrations <1 nM in human leukemia cells, and achieves an IC₅₀ value of 1.5 nM in inhibition of growth of RS4;11 cells. MD-224 has the potential to be a new class of anticancer agent. MD-224 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

Azido-PEG1 is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG1 is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.