HSP Inhibitor

Isoxazole is a member of the five-membered heterocycle drug scaffold. Isoxazole has been used as a BET bromodomain inhibitor and can improve β-cell function in a diabetic mouse model. Isoxazole and its derivatives exhibit broad biological activities (such as antimicrobial, antibacterial, antifungal, antiviral, anticancer, anti-inflammatory, immunomodulatory, analgesic, anti-tuberculosis, and anti-diabetic effects). For example, the bicyclic Isoxazole can act as an HSP90 inhibitor, and the tricyclic Isoxazole is promising as a selective multidrug resistance protein (MRP1) inhibitor​.

PET-16 is a selective HSP70 inhibitor that binds to an allosteric pocket of the substrate-binding domain. PET-16 inhibits the ability of HSP70 to cycle between ATP-bound and ADP-bound states. PET-16 induces apoptosis in multiple myeloma.

Hsp90-Cdc37-IN-1 is an Hsp90-Cdc37 interaction disruptor that inhibit cell migration and reverse agent resistance, with an IC₅₀ of 140 nM.

YZ129 is an inhibitor of the HSP90-calcineurin-NFAT pathway against glioblastoma, directly binding to heat shock protein 90 (HSP90) with an IC₅₀ of 820 nM on NFAT nuclear translocation. YZ129-induced GBM cell-cycle arrest at the G2/M phase promotes apoptosis and inhibited tumor cell proliferation and migration.

XYD049 is a CRBN-based molecular glue degrader targeting GSPT1, with a DC₅₀ of 19 nM. XYD049 mediates the formation of a ternary complex between CRBN and GSPT1, thereby triggering CRBN- and proteasome-dependent degradation of GSPT1. By degrading GSPT1, XYD049 downregulates castration-resistant prostate cancer (CRPC)-related oncogenes, including BCL2, CDK2, E2F3, EGFR, HSP90B1, TMPRSS2, AR, AR-V7, PSA and c-Myc. XYD049 inhibits cancer cell growth and suppresses tumor growth in mice. XYD049 can be used for research on castration-resistant prostate cancer. XYD049 consists of a linker (black part) NH2-C5-NH-Boc (HY-W004710), a CRBN-based E3 ligase ligand (blue part) Thalidomide 4-fluoride (HY-41547), and a target protein ligand (red part) GSPT1 ligand-1 (HY-170821), among which the E3 ligase ligand plus linker forms the conjugate E3 Ligase Ligand-linker Conjugate 158 (HY-170822).

HVH-2930 is a HSP90 C-terminal domain inhibitor with high oral bioavailability. HVH-2930 downregulates HSP90 client proteins, inhibits the HER2 signaling pathway, induces apoptosis, and suppresses the proliferation of breast cancer cells. HVH-2930 inhibits the proliferation of tumors sensitive or resistant to Trastuzumab (HY-P9907). HVH-2930 is applicable to relevant research on breast cancer.

Zelavespib formic (PU-H71 formic) is a potent Hsp90 inhibitor with an IC₅₀ value of 51 nM for Hsp90 in MDA-MB-468 cells.

Adezmapimod (Standard) is the analytical standard of Adezmapimod. This product is intended for research and analytical applications. Adezmapimod (SB 203580) is a selective and ATP-competitive p38 MAPK inhibitor with IC50s of 50 nM and 500 nM for SAPK2a/p38 and SAPK2b/p38β2, respectively. Adezmapimod inhibits LCK, GSK3β and PKBα with IC50s of 100-500-fold higher than that for SAPK2a/p38. Adezmapimod can inhibit p38 MAPK and lead to the inhibition of downstream HSP27 phosphorylation. Adezmapimod does not disrupt JNK activity and is an autophagy and mitophagy activator.

Gamitrinib TPP is a Gamitrinib (GA) mitochondrial matrix inhibitor. Gamitrinib TPP is a mitochondrial targeted HSP90 inhibitor with anti-cancer activity.

DDO-6600 is a covalent Hsp90 inhibitor. DDO-6600 disrupts the interaction between Hsp90 and its co-chaperone protein Cdc37, thereby inducing the degradation of kinase client proteins (such as AKT, CDK4, c-Raf). DDO-6600 has inhibitory activity against various cancer cells. DDO-6600 inhibits the migration and invasion of HCT-116 cells, and induces cell cycle arrest and apoptosis. DDO-6600 significantly inhibits tumor growth in the HCT-116 xenograft tumor model. DDO-6600 can be used for research on colorectal cancer.

HSF1-IN-2 (Compound 0048) is a HSF1 inhibitor. HSF1-IN-2 is applicable to cancer research.

KNK423 is a specific heat shock protein (HSP) synthesis inhibitor. KNK423 improves the efficiency of Amphotericin B in inhibiting resistant Aspergillus terreus by blocking HSP70. KNK423 can be used in cancer and bacterial infection research.

4-Br-Bnlm is a selective inhibitor of glucose-regulated protein 94 (Grp94) with an EC₅₀ value of 0.96 µM. 4-Br-Bnlm reduces the levels of mutant myocilin proteins as well as wild-type myocilin misfold in cells. 4-Br-Bnlm promotes the clearance of toxic formsof myocilin and reduces myocilin toxicity.

Row174336 (compound 29) is a potent inhibitor of Hsp110-STAT3 interaction that shows antiproliferative activity against HPAEC cell line, with the IC₅₀ of 22.67 μM.

KU-177 is a potent inhibitor of Hsp90 ATPase homologue 1 (Aha1), ablates Aha1-driven enhancement of Hsp90-dependent tau aggregation. KU-177 also disrupts Aha1/Hsp90 interactions (IC₅₀=4.08 μM) without inhibition of Hsp90’s ATPase activity. KU-177 can be used for tauopathies research.

Kongensin A is a natural product isolated from Croton kongensis. Kongensin A is an effective, covalent HSP90 inhibitor that blocks RIP3-dependent necroptosishas. Kongensin A is a potent necroptosis inhibitor and an apoptosis inducer. Kongensin A has potential anti-necroptosis and anti-inflammation applications.

Aminohexylgeldanamycin (AHGDM), a Geldanamycin derivative, is a potent HSP90 inhibitor. Aminohexylgeldanamycin shows antiangiogenic and antitumor activities.

Tanespimycin (Standard) is the analytical standard of Tanespimycin. This product is intended for research and analytical applications. Tanespimycin (17-AAG) is a potent HSP90 inhibitor with an IC₅₀ of 5 nM, having a 100-fold higher binding affinity for tumour cell derived HSP90 than normal cell derived HSP90. Tanespimycin depletes cellular STK38/NDR1 and reduces STK38 kinase activity. Tanespimycin also downregulates the stk38 gene expression.

Zinc picolinate is an orally effective zinc supplement. Zinc picolinate reduces the expression of Hsp70, inhibits oxidative DNA damage, increases serum ALP activity, decreases MDA concentration, elevates SOD levels, and raises zinc concentrations in serum, whole body and plasma. Zinc picolinate does not alter copper and manganese contents in rainbow trout. Zinc picolinate exerts a protective effect against Acetic acid (HY-Y0319)-induced experimental colitis in Sprague Dawley rats. Zinc picolinate reduces uterine fibroid volume, alleviates colonic oxidative damage, relieves colonic inflammation, and enhances intestinal barrier integrity. Zinc picolinate can be used in research related to uterine fibroids, ulcerative colitis and chronic obstructive pulmonary disease.

SNX-5422 Mesylate (PF-04929113 Mesylate), a prodrug of SNX-2112, is an orally active Hsp90 inhibitor, with a K_d of 41 nM, and also induces Her-2 degradation, with an IC₅₀ of 37 nM.