Icapamespib hydrochloride
Based on 1 publication(s) in Google Scholar
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.
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- Pureza : 98.74%
- No. CAS: 2267287-26-1
- Fòrmula: C19H25Cl2IN6O2S
- Peso molecular:599.32
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Almacenamiento:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Protocolo
- Pureza y Documentación
- Referencias
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) Icapamespib hydrochloride
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Actividad biológica
Descripciòn
IC50 & Target
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HSP90 |
In Vitro
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. Further protocols information, click here.
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Cell Line:MDA-MB-468, ASPC1
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Concentration:1 μM
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Incubation Time:1 h
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Result:Reduced the formation of high-molecular-weight HSP90 complexes in native-PAGE analysis, while total HSP90 levels remain unchanged in SDS-PAGE, indicating specific disruption of epichaperomes without altering total chaperone expression.
In Vivo
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.
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Animal Model:Female BALB/c nude mice (6-8 weeks old, 18-20 g) bearing U87MG glioblastoma xenografts[1]
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Dosage:10 mg/kg Icapamespib
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Administration:Intravenous injection via tail vein, twice weekly for 3 weeks.
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Result:Significantly reduced tumor volume by 65% compared to vehicle controls.
Decreased levels of HSP90 client proteins (EGFR, AKT) and increased HSP70 expression.
No significant body weight loss or organ toxicity was observed.
Ensayo clínico
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 2267287-26-1
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Appearance Solid
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Peso molecular 599.32
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Fòrmula C19H25Cl2IN6O2S
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Color White to off-white
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SMILES
IC1=C(SC2=NC3=C(N2CCNCC(C)(C)C)N=CN=C3N)C=C4OCOC4=C1.Cl.Cl
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Synonyms
PU-HZ151 hydrochloride
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Publications (1)
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Journal Impact Factor
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Most Recent
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Environ Sci Technol
IodoFinder: Machine Learning-Guided Recognition of Iodinated Chemicals in Nontargeted LC-MS/MS Analysis. [Abstract]2025 Mar 11;59(9):4530-4539. PMID: 40015982
Solvente y solubilidad
In Vitro:
DMSO : 100 mg/mL (166.86 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
H2O : 9.09 mg/mL (15.17 mM; ultrasonic and warming and heat to 60°C)
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.
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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (4.17 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (4.17 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocolo
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Neurotoxicity Study
This protocol assesses in vitro neurotoxicity by combining neuronal viability, mitochondrial/metabolic activity, neurite outgrowth, and optional neuronal network function readouts. Calcein-AM or resazurin/PrestoBlue readouts estimate viable or metabolically active cells; βIII-tubulin immunofluorescence detects neuronal morphology and neurite networks; TMRE detects mitochondrial membrane potential; and MEA recordings detect functional changes in neuronal network activity.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Mammalian live/dead viability and cytotoxicity staining
Live/dead viability and cytotoxicity staining assays are based on the simultaneous detection of intracellular esterase activity in metabolically active (viable) cells and membrane integrity loss in non-viable cells. In commonly used dual-staining approaches, membrane-permeant fluorogenic substrates are converted by intracellular esterases into fluorescent products in live cells, while impermeant DNA-binding dyes selectively enter cells with compromised plasma membranes and label nucleic acids in dead or dying cells, enabling discrimination between viable and non-viable populations by fluorescence microscopy or flow cytometry.
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Pull-down
The pull-down assay is an in vitro technique used to detect physical interactions between two or more proteins and an invaluable tool for confirming a predicted protein-protein interaction or identifying novel interacting partners. This method typically involves the use of affinity purification with various wash and elution steps.
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Immunoprecipitation
Immunoprecipitation (IP) is an experimental method that uses the principle of antibody specific binding to purify and enrich target proteins.
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Protocol for Bimolecular Fluorescence Complementation (BiFC) Assay
Bimolecular fluorescence complementation detects protein-protein proximity in living or fixed cells by fusing two candidate interaction partners to nonfluorescent N- and C-terminal fragments of a fluorescent protein; when the partners interact or remain close enough, the fluorescent fragments complement, mature, and generate a fluorescent signal at the site of the protein complex. The BiFC readout is fluorescence intensity and subcellular localization of the reconstituted fluorophore, which reflects formation or stabilization of a protein complex rather than direct biochemical binding kinetics; BiFC is therefore useful for mapping where interactions occur in cancer cells, neurons, macrophages, organoid-derived cells, or drug-screening systems, but results should be validated by independent assays such as co-IP or Western blot. BiFC signal formation is delayed by fluorophore maturation and can stabilize otherwise transient complexes, so it is not a real-time reversible interaction assay
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
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Co-Immunoprecipitation
Co-immunoprecipitation technology can verify protein interaction based on the specific immune reaction between antibodies and antigens.
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Protocol for Yeast Two-Hybrid (Y2H) Assay
The yeast two-hybrid assay detects binary protein-protein interactions by separating a transcription factor into a DNA-binding domain fused to a "bait" protein and a transcriptional activation domain fused to a "prey" protein; if bait and prey interact in yeast, the transcription factor is reconstituted and activates reporter genes such as HIS3, ADE2, lacZ, MEL1, or other selectable/readable reporters. The readout is yeast growth on selective medium and/or reporter activity, which reflects proximity-dependent transcriptional activation in the yeast nucleus rather than direct biochemical binding in the original mammalian, tumor, neuronal, macrophage, or organoid context. Because yeast two-hybrid can generate false positives and false negatives, interaction claims should be validated using independent assays such as co-immunoprecipitation, Western blot, immunofluorescence colocalization, BiFC, pull-down, or mammalian two-hybrid assays.
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
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Alzheimer’s Disease Modeling
Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by a progressive decline in cognitive functions and loss of specific types of neurons and synapses. Alzheimer's symptoms can be simulated in mice by injecting drugs (such as Aβ) or genetically modified.
Pureza y Documentación
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Ficha de datos (284 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[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]
Complete Stock Solution Preparation Table
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.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| H2O / DMSO | 1 mM | 1.6686 mL | 8.3428 mL | 16.6856 mL | 41.7139 mL |
| 5 mM | 0.3337 mL | 1.6686 mL | 3.3371 mL | 8.3428 mL | |
| 10 mM | 0.1669 mL | 0.8343 mL | 1.6686 mL | 4.1714 mL | |
| 15 mM | 0.1112 mL | 0.5562 mL | 1.1124 mL | 2.7809 mL | |
| DMSO | 20 mM | 0.0834 mL | 0.4171 mL | 0.8343 mL | 2.0857 mL |
| 25 mM | 0.0667 mL | 0.3337 mL | 0.6674 mL | 1.6686 mL | |
| 30 mM | 0.0556 mL | 0.2781 mL | 0.5562 mL | 1.3905 mL | |
| 40 mM | 0.0417 mL | 0.2086 mL | 0.4171 mL | 1.0428 mL | |
| 50 mM | 0.0334 mL | 0.1669 mL | 0.3337 mL | 0.8343 mL | |
| 60 mM | 0.0278 mL | 0.1390 mL | 0.2781 mL | 0.6952 mL | |
| 80 mM | 0.0209 mL | 0.1043 mL | 0.2086 mL | 0.5214 mL | |
| 100 mM | 0.0167 mL | 0.0834 mL | 0.1669 mL | 0.4171 mL |
* 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.
Icapamespib hydrochloride Related Classifications
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