| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
HSP90 Apoptosis
HSP90 C-terminal domain. NCT-58 binds to the C-terminal domain of Hsp90α and inhibits the protein-protein interaction between Hsp90α C-terminal domain and peptidylprolyl isomerase D (PPID), a co-chaperone. It downregulates HER family members and inhibits Akt phosphorylation. |
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| ln Vitro |
In HER2-positive BT474 and SKBR3 cells, NCT-58 treatment (0.1–20 μM; 72 hours) dose-dependently lowers cell viability[1]. HER2-positive BT474 and SKBR3 cells exhibit an increase in early and late apoptotic cells in response to NCT-58 treatment (0.1–10 μM; 72 hours)[1]. In JIMT-1 and MDA-MB-453 cells, NCT-58 treatment (2–10 μM; 72 hours) significantly decreased the amounts of truncated p95HER2 and its phosphorylated version, as well as downregulated the protein contents of Akt and phospho-Akt (Ser473)[1].
NCT-58 induces apoptosis in HER2-positive breast cancer cells. It kills Trastuzumab-resistant breast cancer stem-like cells. It inhibits the proliferation of various cancer cell lines. Detailed IC50 values are available from specialized databases. |
| ln Vivo |
NCT-58 (30 mg/kg; intraperitoneally; every other day for 47 days) inhibits the growth of tumors resistant to trastuzumab[1]. NCT-58 (30 mg/kg; ip; every other day for 47 days) significantly inhibits the growth of tumors and significantly reduces their weight[1].
NCT-58 shows anti-tumor activity via the simultaneous downregulation of HER family members and inhibition of Akt phosphorylation. It is active in vivo and does not induce the heat shock response, which is a common side effect of N-terminal HSP90 inhibitors. |
| Enzyme Assay |
In vitro enzyme assays are performed using recombinant HSP90 protein and a peptide substrate. The ATPase activity of HSP90 is measured using a malachite green phosphate detection assay. The compound is incubated with the enzyme and ATP, and the inhibition of ATP hydrolysis is quantified.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: BT474 and SKBR3 cells Tested Concentrations: 0, 0.1, 0.5, 1, 5, 10, 15, 20 μM Incubation Duration: 72 hrs (hours) Experimental Results: Dramatically decreased cell growth. Apoptosis Analysis[1] Cell Types: BT474 and SKBR3 cells Tested Concentrations: 0, 2, 10 μM Incubation Duration: 72 hrs (hours) Experimental Results: Increased the number of early and late apoptotic cells. Western Blot Analysis[1] Cell Types: Trastuzumab-resistant JIMT-1 and MDA-MB-453 cells Tested Concentrations: 0, 2, 10 μM Incubation Duration: 72 hrs (hours) Experimental Results: Effectively decreased the levels of truncated p95HER2 and its phosphorylated form, as well as downregulation of Akt and phospho-Akt (Ser473) protein contents in JIMT-1 and MDA-MB-453 cells. Cells (e.g., HER2-positive breast cancer cells) are treated with NCT-58. Cell viability is measured using MTT or CellTiter-Glo assays. Apoptosis is assessed by Annexin V/PI staining. HER2 and Akt phosphorylation levels are measured by Western blotting. |
| Animal Protocol |
Animal/Disease Models: Trastuzumab-resistant xenograft model (female nude mice; 6 weeks; BALB/c )[1]
Doses: 30 mg/kg Route of Administration: ip; every other day for 47 days Experimental Results: Dramatically diminished tumor growth. In vivo efficacy studies are conducted in mouse xenograft models using HER2-positive breast cancer cells. NCT-58 is administered orally or intraperitoneally. Tumor volume is measured by calipers. Tumors are harvested for histology and biomarker analysis. Body weight and clinical signs are monitored. |
| ADME/Pharmacokinetics |
NCT-58 has a molecular weight of 466.57 and a molecular formula of C27H34N2O5. It is soluble in DMSO. Detailed pharmacokinetic parameters such as oral bioavailability and half-life are available from specialized databases. It is stored at -20°C.
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| Toxicity/Toxicokinetics |
Detailed toxicological profiles of NCT-58 are not extensively reported. In vivo studies show that it is tolerated at efficacious doses. Unlike N-terminal HSP90 inhibitors, NCT-58 does not induce the heat shock response, which may reduce certain toxicities associated with HSP90 inhibition.
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| References | |
| Additional Infomation |
NCT-58 is a research-grade C-terminal HSP90 inhibitor. It is used in cancer research, particularly in breast cancer. It is not approved for clinical use. Its molecular formula is C27H34N2O5 and its molecular weight is 466.57.
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| Molecular Formula |
C27H34N2O5
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|---|---|
| Molecular Weight |
466.57
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| Exact Mass |
466.25
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| Elemental Analysis |
C, 69.51; H, 7.35; N, 6.00; O, 17.15
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| CAS # |
2411429-33-7
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| PubChem CID |
149033485
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| Appearance |
White to off-white solid powder
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
34
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| Complexity |
699
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(C)(C)OC2=CC=C(C(NC3=CC=C(OCCC4CCCCN4)C(OC)=C3)=O)C(OC)=C2C=C1
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| InChi Key |
QGEKYFVMAGLOKW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H34N2O5/c1-27(2)14-12-20-22(34-27)11-9-21(25(20)32-4)26(30)29-19-8-10-23(24(17-19)31-3)33-16-13-18-7-5-6-15-28-18/h8-12,14,17-18,28H,5-7,13,15-16H2,1-4H3,(H,29,30)
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| Chemical Name |
5-methoxy-N-(3-methoxy-4-(2-(piperidin-2-yl)ethoxy)phenyl)-2,2-dimethyl-2H-chromene-6-carboxamide
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| Synonyms |
NCT-58; NCT 58; NCT58;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 50 mg/mL (107.17 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1433 mL | 10.7165 mL | 21.4330 mL | |
| 5 mM | 0.4287 mL | 2.1433 mL | 4.2866 mL | |
| 10 mM | 0.2143 mL | 1.0717 mL | 2.1433 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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