Cat. No.: HY-164548

WK88-1

WK88-1 is an apoptosis inducer and Hsp90 client protein inhibitor with antiproliferative and immunomodulatory activities. WK88-1 inhibits signaling pathways such as PI3K/Akt and NF-κB, and induces mitochondrial dysfunction and cell cycle arrest. WK88-1 effectively suppresses cancer cell migration and invasion, and reverses various EGFR mutations and resistance to Gefitinib (HY-50895). WK88-1 also regulates the differentiation of monocytes and dendritic cells, blocks the expression of multiple chemokines, inhibits immune cell migration and M1 marker transcription, and restores impaired endocytic activity. WK88-1 has been used in studies of breast cancer, non-small cell lung cancer with various EGFR mutations or Met amplification, and atherosclerosis and other related diseases.

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CAS No.: 958888-32-9
Formule: C₂₈H₄₂N₂O₆
Masse moléculaire:502.64

Stockage:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (284 KB)

WK88-1 Chemical Structure

CAS No.: 958888-32-9

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Activité biologique
- Description
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
Pureté et documentation
Références
Calculators
Help & FAQs
Classifications
Bioz

Activité biologique

Description

IC₅₀ & Target

^[1]

HSP90

Voir tous les produits spécifiques à Isoform HSP :

Voir tous les produits spécifiques à Isoform PI3K :

Voir tous les produits spécifiques à Isoform Akt :

Voir tous les produits spécifiques à Isoform NF-κB :

In Vitro

WK88-1 (0.078-100 μM; 24-72 h) potently inhibits proliferation of human ER-positive MCF-7 breast cancer cells^[1].
WK88-1 (50.0 μM; 48 h) induces G₂/M phase cell cycle arrest in human ER-positive MCF-7 breast cancer cells and human ER-negative MDA-MB-231 breast cancer cells, associated with downregulation of CDK1 and cyclin B1 proteins^[1].
WK88-1 (0.1-5 μM; 24 h) inhibits Hsp90 function in gefitinib-resistant H1975 (EGFR^L858R/T790M) cells, inducing dose-dependent degradation of oncogenic receptor tyrosine kinases (EGFR, ErbB2, ErbB3, Met) and downstream signaling proteins (Akt), while upregulating Hsp70^[2].
WK88-1 (0.5-1 μM; 24 h) induces dose-dependent early apoptosis in gefitinib-resistant H1975 (EGFR^L858R/T790M) cells, with early apoptosis reaching 22.23% at 1 μM^[2].
WK88-1 (1-5 μM; 24 h) potently suppresses the migration of gefitinib-sensitive HCC827 and gefitinib-resistant Met-amplified HCC827GR non-small cell lung cancer cells^[3].
WK88-1 (1-5 μM; 48 h) potently suppresses the invasion of gefitinib-sensitive HCC827 and gefitinib-resistant Met-amplified HCC827GR non-small cell lung cancer cells^[3].
WK88-1 (1 μg/mL; 48 h) inhibits 27-hydroxycholesterol-induced transcription of M1 cytokines CXCL10, CXCL11, and TNF-α in THP-1 human monocytic cells^[4].
WK88-1 (1 μg/mL; 4 h) inhibits 27-hydroxycholesterol-induced Akt phosphorylation in THP-1 human monocytic cells^[4].

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

Cell Cycle Analysis^[1]

Cell Line:

human ER-positive MCF-7 breast cancer cells, human ER-negative MDA-MB-231 breast cancer cells
Concentration:

1.25-50 μM (flow cytometry); 3.125-50 μM (western blot analysis)
Incubation Time:

48 h (flow cytometry)
Result:

Increased the proportion of cells in the G₂/M phase by 37.2% in MCF-7 cells and 39.4% in MDA-MB-231 cells at 50.0 μM compared to vehicle controls.
Downregulated the levels of cell cycle regulatory proteins CDK1 and cyclin B1 in both cell lines.

Apoptosis Analysis^[1]

Cell Line:

human ER-positive MCF-7 breast cancer cells, human ER-negative MDA-MB-231 breast cancer cells
Concentration:

3.125-50 μM (DAPI staining); 50 μM (PI flow cytometry); 3.125-50 μM (Annexin V/PI dual staining)
Incubation Time:

48 h
Result:

Induced concentration-dependent nuclear condensation and apoptotic bodies in both cell lines via DAPI staining.
Detected apoptosis rates of 43.8% in MCF-7 cells and 31.6% in MDA-MB-231 cells at 50.0 μM.
Showed late apoptotic cell proportions of 34.9% in MCF-7 cells and 27.9% in MDA-MB-231 cells at 25.0 μM.
Caused no obvious change in early apoptotic cell proportions across tested concentrations compared to controls.

Cell Migration Assay ^[3]

Cell Line:

gefitinib-sensitive HCC827 non-small cell lung cancer cells, gefitinib-resistant HCC827GR (Met-amplified) non-small cell lung cancer cells
Concentration:

1 μM, 5 μM
Incubation Time:

24 h
Result:

Strongly abrogated the migratory capacity of both HCC827 and HCC827GR cells in a concentration-dependent manner.
Caused statistically significant inhibition of migration at both 1 μM and 5 μM compared to vehicle controls.

Cell Invasion Assay^[3]

Cell Line:

gefitinib-sensitive HCC827 non-small cell lung cancer cells, gefitinib-resistant HCC827GR (Met-amplified) non-small cell lung cancer cells
Concentration:

1 μM, 5 μM
Incubation Time:

48 h
Result:

Potently inhibited the invasive capacity of both HCC827 and HCC827GR cells in a concentration-dependent manner.
Caused statistically significant inhibition of invasion at both 1 μM and 5 μM compared to vehicle controls.

In Vivo

WK88-1 causes no detectable hepatotoxicity in C57BL/6 mice^[1].
WK88-1 (1 mg/kg; injection; 3 times/week) produces significant antitumor efficacy in athymic nude mice bearing H1975 xenografts, with reductions in tumor volume and weight^[2].
WK88-1 (1 mg/kg; i.p.; three times per week) significantly inhibits the growth of gefitinib-resistant non-small cell lung cancer xenografts in nude mice, reducing tumor weight by 50%^[3].
WK88-1 (10-30 mg/kg; i.v.; twice at 24 h intervals) does not induce hepatotoxicity in healthy C57BL/6 mice, as indicated by stable body weight and normal plasma GOT and GPT levels^[3].

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

Animal Model:

BALB/c-nu athymic nude mice (male, 5 weeks old, subcutaneous xenograft with gefitinib-resistant HCC827GR cells)^[3]
Dosage:

1 mg/kg
Administration:

i.p.; three times per week
Result:

Caused a significant decrease in tumor volume relative to controls, with statistically significant differences observed on day 7, day 10, and day 13.
Reduced tumor weight to ~0.5 g, representing a significant 50% reduction compared to ~1.0 g in control mice.

Related Protocols :

Chemical Information

CAS No. 958888-32-9
Masse moléculaire 502.64
Formule C₂₈H₄₂N₂O₆
SMILES

C/C(C(NC1=CC2=CC=C1)=O)=C/CC[C@H](OC)[C@@H](OC(N)=O)/C(C)=C/[C@H](C)[C@H]([C@@H](OC)C[C@@H](C2)C)O
Livraison

Room temperature in continental US; may vary elsewhere.
Stockage

Please store the product under the recommended conditions in the Certificate of Analysis.

Pureté et documentation

Select Batch:

Pureté: 99.98%

Assay: 99.98%

ee.: 99.98%

Fiche technique (284 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Instruction de manipulation (2659 KB)

Références

[1]. Zhao YR, et al. Non-Benzoquinone Geldanamycin Analog, WK-88-1, Induces Apoptosis in Human Breast Cancer Cell Lines. J Microbiol Biotechnol. 2018;28(4):542-550. [Content Brief]

[2]. Hong YS, et al. Hsp90 inhibition by WK88-1 potently suppresses the growth of gefitinib-resistant H1975 cells harboring the T790M mutation in EGFR. Oncol Rep. 2014;31(6):2619-2624. [Content Brief]

[3]. Jang WJ, et al. Anti-tumor activity of WK88-1, a novel geldanamycin derivative, in gefitinib-resistant non-small cell lung cancers with Met amplification. Cancer Sci. 2014;105(10):1245-1253. [Content Brief]

[4]. Choi J, et al. Reblastatins Inhibit Phenotypic Changes of Monocytes/Macrophages in a Milieu Rich in 27-Hydroxycholesterol. Immune Netw. 2020;20(2):e17. Published 2020 Apr 23. [Content Brief]

[5]. Wan X, et al. GW4869 can inhibit epithelial-mesenchymal transition promoted by extracellular HSP90α in EGFR-mutated NSCLC cells[J]. 2022.

Calculators

Calculateur de molarité

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Calculateur de dilution

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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WK88-1

Voir tous les produits spécifiques à Isoform HSP

Voir tous les produits spécifiques à Isoform PI3K

Voir tous les produits spécifiques à Isoform Akt

Voir tous les produits spécifiques à Isoform NF-κB