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PROTAC

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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.

Research Areas

Products Related to PROTAC(338)

  • GC33238 structure
    GC33238SJFδ
    CAS: 2254609-23-7
    Purity: >98.00%

    SJFδ is a 10-atom linker PROTAC based on von Hippel-Lindau ligand. SJFδ degrades p38δ with a DC50 of 46.17nM, but does not degrade p38α, p38β, or p38γ.

  • GC33280 structure
    GC33280A1874
    CAS: 2064292-12-0
    Purity: >98.00%

    A1874 is a nutlin-based (MDM2 ligand) and BRD4-degrading PROTAC with a DC50 of 32 nM (induce BRD4 degradation in cells). Effective in inhibiting many cancer cell lines proliferation.

  • GC33354 structure
    GC33354AT6
    CAS: 2098836-50-9
    Purity: >99.50%

    AT6 is a PROTAC AT1 analogue, which is a PROTAC connected by ligands for von Hippel-Lindau and BRD4 with highly selectivity to bromodomain (Brd4).

  • GC33363 structure
    GC33363MZP-55
    CAS: 2010159-48-3
    Purity: >99.00%

    MZP-55 is a PROTAC connected by ligands for von Hippel-Lindau and BRD3/4, with a Kd of 8 nM for Brd4BD2.

  • GC33372 structure
    GC33372PROTAC BRD9 Degrader-1
    CAS: 2097971-01-0
    Purity: >98.00%

    PROTAC BRD9 Degrader-1 is a PROTAC connected by ligands for Cereblon and BRD9 (IC50=13.5 nM), which can be used as a selective probe useful for the study of BAF complex biology.

  • GC33391 structure
    GC33391Homo-PROTAC cereblon degrader 1
    CAS: 2244520-98-5
    Purity: >99.00%

    Homo-PROTAC cereblon degrader 1 (compound 15a) is a highly potent and efficient Cereblon (CRBN) degrader with only minimal effects on IKZF1 and IKZF3.

  • GC33418 structure
    GC33418PROTAC Sirt2 Degrader-1
    CAS: 2098487-75-1
    Purity: >98.50%

    PROTAC Sirt2 Degrader-1 is a SirReal-based PROTAC, acts as a Sirt2 degrader, composed of a highly potent and isotype-selective Sirt2 inhibitor, a linker, and a bona fide Cereblon ligand for E3 ubiquitin ligase. PROTAC Sirt2 Degrader-1 shows an IC50 of 0.25 μM for Sirt2, with no effect on Sirt1/Sirt3 (IC50s>100 μM).

  • GC34319 structure
    GC34319TD-428
    CAS: 2334525-50-5
    Purity: >98.00%

    TD-428 is a PROTAC connected by ligands for Cereblon and BRD4. TD-428 is a highly specific BRD4 degrader with a DC50?of?0.32?nM. TD-428 is a BET PROTAC, which comprises TD-106 (a CRBN ligand) linked to JQ1 (a BET inhibitor). TD-428 efficiently induce BET protein degradation.

  • GC34325 structure
    GC34325PROTAC BET degrader-3
    Purity: >98.50%

    PROTAC BET Degrader-3 is a PROTAC connected by ligands for von Hippel-Lindau and BET.

  • GC34341 structure
    GC34341PROTAC ERα Degrader-1
    CAS: 2417369-94-7
    Purity: >98.00%

    PROTAC ERα Degrader-1 comprises an ubiquitin E3 ligase binding group, a linker and a protein binding group. PROTAC ERα Degrader-1 extracts from patent WO2017201449A1, compound P1. PROTAC ERα Degrader-1 is an estrogen receptor-alpha (ERα) degrader.

  • GC34730 structure
    GC34730PROTAC CRABP-II Degrader-1
    CAS: 1225383-40-3
    Purity: >98.00%

    PROTAC CRABP-II Degrader-1 is a potent cellular retinoic acid binding protein (CRABP-II) degrader based on IAP ligand.

  • GC34731 structure
    GC34731PROTAC CRABP-II Degrader-2
    CAS: 1225383-38-9
    Purity: >98.00%

    PROTAC CRABP-II Degrader-2 is a potent cellular retinoic acid binding protein (CRABP-II) degrader based on IAP ligand.

  • GC34732 structure
    GC34732PROTAC CRABP-II Degrader-3
    CAS: 1225383-41-4
    Purity: >98.00%

    PROTAC CRABP-II Degrader-3 is a potent cellular retinoic acid binding protein (CRABP-II) degrader based on IAP ligand.

  • GC34733 structure
    GC34733PROTAC ER Degrader-2
    CAS: 1351169-29-3
    Purity: >98.00%

    PROTAC ER Degrader-2 is an intermediate for synthesis of PAC. PAC, consists the ADCs linker and PROTACs, conjugated to an antibody. PAC extracts from patent WO2017201449A1, compound LP2. PAC conjugated to an antibody is a more marked estrogen receptor-alpha (ERα) degrader compared to PROTAC (without Ab).

  • GC34734 structure
    GC34734PROTAC ER Degrader-3
    CAS: 2158322-29-1
    Purity: >98.00%

    PROTAC ER Degrader-3 is an intermediate for synthesis of PAC. PAC, consists the ADCs linker and PROTACs, conjugated to an antibody. PAC extracts from patent WO2017201449A1, compound LP2. PAC conjugated to an antibody is a more marked estrogen receptor-alpha (ERα) degrader compared to PROTAC (without Ab).

  • GC34735 structure
    GC34735PROTAC ERα Degrader-2
    CAS: 1351169-29-3
    Purity: >98.00%
  • GC34740 structure
    GC34740PROTAC RAR Degrader-1
    CAS: 1351169-27-1
    Purity: >98.00%

    PROTAC RAR Degrader-1 comprises a IAP ligand binding group, a linker and a RAR ligand binding group. PROTAC RAR Degrader-1 is an RAR degrader. Maximal RAR degradation at 30 μM concentration in HT1080 cells. Degradation inducers based on cIAP1 are called specific and non-genetic IAP-dependent protein erasers (SNIPERs).

  • GC35227 structure
    GC35227ACBI1
    CAS: 2375564-55-7
    Purity: >98.00%

    ACBI1 is a potent and cooperative SMARCA2, SMARCA4 and PBRM1 degrader with DC50s of 6, 11 and 32 nM, respectively. ACBI1 is a PROTAC degrader. ACBI1 shows anti-proliferative activity. ACBI1 induces apoptosis.

  • GC35635 structure
    GC35635CDK9 Antagonist-1
    Purity: >98.00%
  • GC35739 structure
    GC35739CP-10
    CAS: 2366268-80-4
    Purity: >98.00%

    CP-10 is a PROTAC connected by ligands for Cereblon and CDK, with highly selective, specific, and remarkable CDK6 degradation (DC50=2.1 nM). It inhibits proliferation of several haematopoietic cancer cells with impressive potency including multiple myeloma, and can still degrades mutated and overexpressed CDK6.

  • GC35815 structure
    GC35815dBET57
    CAS: 1883863-52-2
    Purity: >99.50%

    dBET57 is a potent and selective degrader of BRD4BD1 based on the PROTAC technology. dBET57 mediates recruitment to the CRL4Cereblon E3 ubiquitin ligase, with a DC50/5h of 500 nM for BRD4BD1, and is inactive on BRD4BD2.

  • GC35882 structure
    GC35882dMCL1-2
    CAS: 2351218-88-5
    Purity: >98.00%

    dMCL1-2 is a potent and selective PROTAC of myeloid cell leukemia 1 (MCL1) (Bcl-2 family member) based on Cereblon, which binds to MCL1 with a KD of 30 nM. dMCL1-2 activats the cellular apoptosis machinery by degradation of MCL1.

  • GC35904 structure
    GC35904dTRIM24
    CAS: 2170695-14-2
    Purity: >99.50%

    dTRIM24 is a selective bifunctional degrader of TRIM24 based on PROTAC, consists of ligands for von Hippel-Lindau and TRIM24.

  • GC36001 structure
    GC36001ERD-308
    CAS: 2320561-35-9
    Purity: >99.00%

    ERD-308 is a highly potent von Hippel-Lindau-based PROTAC degrader of estrogen receptor (ER) for ER positive breast cancer treatment. ERD-308 induces >95% of ER degradation at concentrations as low as 5 nM in both cell lines (DC50 (concentration causing 50% of protein degradation) of 0.17 nM and 0.43 nM in MCF-7 and T47D ER+ cells, respectively).