2. PROTAC
  3. Ligands for E3 Ligase

Ligands for E3 Ligase

A PROTAC (Proteolysis Targeting Chimeric Molecule) is a protein degrader comprised of a ligand for E3 ligase (E3 ligase binder), a linker and a ligand for target protein (target binder). The association between an E3 ligase and a target protein induced by a PROTAC will lead to the transfer of ubiquitin and degradation of the targeted protein.

E3 ligases catalyze the transfer of ubiquitin to targeted proteins and determine the specificity of the proteins. There are hundreds of E3 ligases in cells, but only a limited number of them are successfully used in reported PROTACs, such as VHL (von Hippel-Lindau disease tumor suppressor protein), CRBN (Cereblon), MDM2 (the mouse double minute 2 homologue) and IAP (inhibitor of apoptosis).

Ligands for E3 Ligase Related Products (333):

Cat. No. Product Name Effect Purity
  • HY-130800
    Eragidomide Modulator 99.76%
    Eragidomide (CC-90009) is a first-in-class GSPT1-selective cereblon (CRBN) E3 ligase modulator, acts as a molecular glue. Eragidomide coopts the CRL4CRBN to selectively target GSPT1 for ubiquitination and proteasomal degradation[1][2].
  • HY-14658
    Thalidomide 99.92%
    Thalidomide inhibits cereblon (CRBN), a part of the cullin-4 E3 ubiquitin ligase complex CUL4-RBX1-DDB1, with a Kd of ∼250 nM, and has immunomodulatory, anti-inflammatory and anti-angiogenic cancer properties. Thalidomide can work as molecular glue to potentiate substrate.
  • HY-10984
    Pomalidomide
    Pomalidomide, the third-generation immunomodulatory agent, acts as molecular glue. Pomalidomide interacts with the E3 ligase cereblon and induces degradation of essential Ikaros transcription factors.
  • HY-101488
    CC-885 99.85%
    CC-885 is a cereblon (CRBN) modulator with potent anti-tumour activity. CC-885 is also a known degrader of GSPT1, inhibiting protein translation.
  • HY-A0003
    Lenalidomide 99.91%
    Lenalidomide (CC-5013), a derivative of Thalidomide, acts as molecular glue. Lenalidomide is an orally active immunomodulator. Lenalidomide (CC-5013) is a ligand of ubiquitin E3 ligase cereblon (CRBN), and it causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. Lenalidomide (CC-5013) specifically inhibits growth of mature B-cell lymphomas, including multiple myeloma, and induces IL-2 release from T cells[1][2].
  • HY-150803
    VHL Ligand 14 99.93%
    VHL Ligand 14 (Compound 11) is a VHL ligand for design of PROTAC estrogen receptor α (ERα) degraders, with a binding affinity IC50 of 196 nM[1].
  • HY-160555A
    (S,R,S)-AHPC-CO-C9-NH2 hydrochloride 98.79%
    (S,R,S)-AHPC-CO-C9-NH2 (hydrochloride) is a von Hippel-Lindau (VHL) amino building block that can be used to synthesize E3 ligase ligands required for PROTACs..
  • HY-160695
    PT-179
    PT-179 is an orthogonal Thalidomide (HY-14658) derivative that targets cereblon without causing off-target degradation effects. PT-179 is able to specifically bind CRBN, form a ternary complex with a target protein fused to a zinc finger (ZF) degron, and mediate the degradation of the tagged protein. For example, PT-179 binds to the ubiquitin ligase substrate receptor cereblon by forming a complex with SD40 and efficiently degrades proteins N- or C-terminally fused to SD40 or SD36 (DC50 for eGFP: 4.5 nM and 14.3 nM). PT-179 can be used to develop compact protein degradation tagging platforms[1].
  • HY-161130
    Lenalidomide 4'-PEG3-amine dihydrochloride
    Lenalidomide 4'-PEG3-amine dihydrochloride is the Lenalidomide-based Cereblon ligand used in the recruitment of CRBN protein. Lenalidomide 4'-PEG3-amine dihydrochloride can be connected to the ligand for protein by a linker to form PROTAC[1].
  • HY-41547
    Thalidomide 4-fluoride
    Thalidomide 4-fluoride (Cereblon ligand 4) is the Thalidomide-based Cereblon ligand used in the recruitment of CRBN protein. Thalidomide 4-fluoride (Cereblon ligand 4) can be connected to the ligand for IRAK4 protein by a linker to form PROTAC IRAK4 degrader-1 (HY-129966)[1].
  • HY-123215
    CC-17369 98.13%
    CC-17369 (7-Hydroxy pomalidomide) is a metabolite of Pomalidomide. CC-17369 is the Pomalidomide -based cereblon (CRBN) ligand used in the recruitment of CRBN protein. CC-17369 can be connected to the ligand for protein by a linker to form PROTAC[1].
  • HY-10984S2
    Pomalidomide-d4
    Pomalidomide-d4 is the deuterium labeled Pomalidomide. Pomalidomide, the third-generation immunomodulatory agent, acts as molecular glue. Pomalidomide interacts with the E3 ligase cereblon and induces degradation of essential Ikaros transcription factors<
  • HY-157756
    E3 Ligase Ligand-linker Conjugate 104
    E3 Ligase Ligand-linker Conjugate 104 is a conjugate of E3 ligase ligand and linker, consisting of Thalidomide (HY-14658) and the corresponding Linker. E3 Ligase Ligand-linker Conjugate 104 can serve as Cereblon ligand to recruit CRBN protein and serve as a key intermediate for the synthesis of complete PROTAC molecules.
  • HY-145776
    ALV1
    ALV1 potently induces degradation of both Ikaros and Helios without unexpected off-target activity. ALV1 binds CRBN with IC50 of 0.55 µM. ALV1 degrades cells stably expressing IKZF1Δ and IKZF2Δ GFP fusions with mCherry reporter with DC50s of 2.5 and 10.3 nM[1].
  • HY-161185
    Thalidomide-piperidine-O-azetidine-boc
    Thalidomide-piperidine-O-azetidine-boc is a conjugate of E3 ubiquitin ligase ligand-Linker, which can be used to synthesize complete PROTACs molecules.
  • HY-125845
    (S,R,S)-AHPC 99.13%
    (S,R,S)-AHPC (VH032-NH2) is the VH032-based VHL ligand used in the recruitment of the von Hippel-Lindau (VHL) protein. (S,R,S)-AHPC can be connected to the ligand for protein (e.g., BCR-ABL1) by a linker to form PROTACs (e.g., GMB-475). GMB-475 induces the degradation of BCR-ABL1 with an IC50 of 1.11 μM in Ba/F3 cells[1].
  • HY-162197
    E3 ligase Ligand-Linker Conjugate 41
    E3 ligase Ligand-Linker Conjugate 41 is a conjugate of E3 ligase ligand and linker, consisting of Thalidomide (HY-14658) and the corresponding Linker. E3 ligase Ligand-Linker Conjugate 41 can serve as a Cereblon ligand to recruit CRBN protein and serve as a key intermediate for the synthesis of complete PROTAC molecules.
  • HY-157600
    E3 ligase Ligand-Linker Conjugate 66
    E3 ligase Ligand-Linker Conjugate 66 is a conjugate of E3 ligase ligand and linker, consisting of Thalidomide (HY-14658) and the corresponding Linker. E3 ligase Ligand-Linker Conjugate 66 can serve as a Cereblon ligand to recruit CRBN protein and serve as a key intermediate for the synthesis of complete PROTAC molecules.
  • HY-156164
    Thalidomide-5-NH-PEG2-NH2 hydrochloride
    Thalidomide-5-NH-PEG2-NH2 hydrochloride is a Thalidomide (HY-14658)-based cereblon ligand that recruits CRBN proteins. Thalidomide-5-NH-PEG2-NH2 hydrochloride can be connected to the target protein ligand through a linker to form a PROTAC molecule. For example, THAL-SNS-032 (HY-123937).
  • HY-157758
    (S)-Thalidomide-piperazine-pyrimidine-piperazine-C2-O-CH2-COO-C(CH3)3
    (S)-Thalidomide-piperazine-pyrimidine-piperazine-C2-O-CH2-COO-C(CH3)3 is a conjugate of E3 ligase ligand and linker, consisting of Thalidomide (HY-14658) and the corresponding Linker . (S)-Thalidomide-piperazine-pyrimidine-piperazine-C2-O-CH2-COO-C(CH3)3 can serve as a Cereblon ligand to recruit CRBN protein and serve as a key intermediate for the synthesis of complete PROTAC molecules.