Icapamespib hydrochloride  (Synonyms: PU-HZ151 hydrochloride)

Icapamespib (PU-HZ151; PU-AD) hydrochloride is a selective, orally active inhibitor of Epichaperomes assembled by HSP90 with slow dissociation kinetics. Icapamespib hydrochloride can cross the blood-brain barrier (BBB) ??and induce epichaperome disassembly by non-covalently binding to HSP90, restoring the normal protein-protein interaction network. Icapamespib hydrochloride can specifically disrupt disease-related abnormal protein interaction networks, reduce neurotoxic protein aggregation and tumor cell survival signals. Icapamespib hydrochloride can be used in the research of neurodegenerative diseases such as Alzheimer's disease, as well as cancers such as glioblastoma and metastatic breast cancer^[1][2][3].

Icapamespib hydrochloride has an EC₅₀ of 5 nM for epichaperomes in MDA-MB-468 cell homogenates, with a higher binding affinity than PU-H71 (EC₅₀ of 11 nM)^[1].
Icapamespib hydrochloride (0.1-1 μM; 24 h) significantly reduces MDA-MB-468 cell viability and reduces high molecular weight HSP90 complexes by disrupting epichaperome structure, while inducing decreased p-ERK phosphorylation levels and c-PARP cleavage^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Icapamespib (10 mg/kg; intravenous injection; twice a week; 3 weeks) hydrochloride significantly inhibits tumor growth in the human glioblastoma U87MG nude mouse model, reduces tumor volume, without obvious toxicity^[1].
Icapamespib hydrochloride can target Alzheimer's disease and pedicled blastoma^[2].
124I-labeled Icapamespib hydrochloride derivatives have been used to detect and quantify Epichaperomes in vivo by PET imaging^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

599.32

C₁₉H₂₅Cl₂IN₆O₂S

2267287-26-1

Solid

White to off-white

IC1=C(SC2=NC3=C(N2CCNCC(C)(C)C)N=CN=C3N)C=C4OCOC4=C1.Cl.Cl

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

• [1]. Bolaender A, et al. Chemical tools for epichaperome-mediated interactome dysfunctions of the central nervous system. Nat Commun. 2021;12(1):4669. Published 2021 Aug 3.  [Content Brief]

  [2]. Pasala C, et al. Epichaperomes: redefining chaperone biology and therapeutic strategies in complex diseases. RSC Chem Biol. 2025 Mar 19;6(5):678-698.  [Content Brief]

  [3]. Bay S, et al. Synthesis and Characterization of Click Chemical Probes for Single-Cell Resolution Detection of Epichaperomes in Neurodegenerative Disorders. Biomedicines. 2024 Jun 4;12(6):1252.  [Content Brief]