HSP Ligand

HSF1 ligand-1 (compound 18) is a ligand for heat shock transcription factor HSF1, as well as a binder for the high-affinity nuclear protein pirin, with an SPR K_d of 44 nM. HSF1 ligand-1 can be used to prepare HSF1-targeted PROTAC degrader (HY-122653).

HSP70 ligand 1, a HSP70 ligand, is a ligand for the target protein of PROTAC. HSP70 ligand 1 can be used to synthesize PROTAC HSP70 Degrader-1 (HY-181147).

HSP70 ligand 2 is an HSP70 ligand and serves as a ligand for PROTAC target proteins. HSP70 ligand 2 can be used to synthesize Hsp70TAC BRD4 Degrader-1 (HY-182958) and Hsp70TAC PD-1 Degrader-2 (HY-182959).

Chaperone complex ligand 1 is a chaperone ligand for HSP90. Chaperone complex ligand 1 can be connected to the MET ligand (HY-50878) by a linker to synthesis of MET degrader OZD-MET 01 (HY-177893).

NBE5 is an orally active hydrophobic tag-targeting (Hyt) degrader (HyTTD) that targets Keap1. NBE5 mimics protein misfolding and recruits the molecular chaperone Hsp90, while achieving targeted degradation of Keap1 through both the ubiquitin-proteasome system and the autophagy-lysosome system. Consequently, NBE5 relieves the inhibition of the transcription factor Nrf2 by Keap1, potently activates the Nrf2-mediated endogenous antioxidant pathway, and upregulates the expression of downstream antioxidant proteins such as HO-1 and GCLM. NBE5 effectively alleviates oxidative stress and inflammatory damage, and exhibits excellent in vivo activity in a mouse model of acute colitis induced by DSS (HY-116282C).
NBE5 consists of a hydrophobic tag (HY-W022007), a Keap1-Nrf2 ligand (HY-14909), and a linker (HY-W014831).

HSP90i-COCH2CH2-PEG4-NHBoc is a conjugate of the HSP90 Ligand (HY-174476) and the linker (HY-W021787). HSP90i-COCH2CH2-PEG4-NHBoc can be used for synthesis of LYTACs, such as dPDL1-4 (HY-174468).

dPDL1-4 is a potent and selective eHSPTAC eHSP90 PD-L1 degrader with DC₅₀s of 7.77 μM and 6.52 μM in HeLa and B16F10 cells. dPDL1-4 bridges eHSP90 with the target protein, inducing lysosomal degradation. dPDL1-4 can degrade PD-L1 significantly and inhibits tumor growth. dPDL1-4 can be used for the study of cervical cancer and melanoma. ((Pink: eHSP90 ligand (HY-174476); Blue: PD-L1 ligand (HY-116274); Black: Linker (HY-W021787); HSP ligand + linker: HY-174799)).

Hsp70TAC BRD4 Degrader-1 is a degrader targeting BRD4, with a K_D value of 0.22 μM. Hsp70TAC BRD4 Degrader-1 forms a ternary complex with Hsp70 (K_D: 5.13 μM), and specifically and efficiently degrades intracellular BRD4 via the ubiquitin-proteasome pathway. Hsp70TAC BRD4 Degrader-1 exhibits potent anti-tumor proliferative activity. Hsp70TAC BRD4 Degrader-1 can be used in studies related to triple-negative breast cancer and glioblastoma multiforme. (Pink: BRD4 ligand (HY-78695); Blue: HSP70 ligand (HY-182979); Black: linker (HY-B0236)).