HBS-101
Based on 1 Customer Validation
HBS-101 is a selectively, orally active, brain-penetrant, Midkine (MDK) inhibitor (KD = 38.4 nM). HBS-101 significantly reduces cell viability, clonogenic survival, and invasiveness and increases apoptosis. HBS-101 involves suppression of the Akt/mTOR, STAT3, and NF-κB pathways. HBS-101 can be used for the study of Triple-negative breast cancer (TNBC).
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- Pureza : 99.59%
- Fòrmula: C21H24F2O2
- Peso molecular:346.41
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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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
Actividad biológica
Descripciòn
In Vitro
HBS-101 (0.1-10 μM, 5 days) significantly reduces cell viability of TNBC cell lines[1].
HBS-101 (0-5 μM) reduces the colony-forming ability of TNBC cells in a dose-dependent manner[1].
HBS-101 (20 μM, 24 h) induces apoptosis in TNBC cells, but not in normal mammary epithelial cells[1].
HBS-101 (20 μM, 20 h) significantly reduces the expression of MDK receptors, specifically Notch2, in HCC-70 cells; inhibits downstream signaling pathways, including mTOR, STAT3, and NF-κB; and increases cleaved caspase-3 levels[1].
HBS-101 (20 μM, 24 h) downregulates MDK target genes and significantly reduces STAT3 and NF-κB reporter activity in TNBC cells that stably express these reporters[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:SUM-159, BT-549, MDA-MB-468, MDA-MB-231, MDA-MB-231-BrM2-831, HCC-70, HCC-1937, HER2+ SKBR3, ER+ MCF7, MCF10A
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Concentration:0.1 μM, 1 μM, 10 μM
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Incubation Time:5 days
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Result:Significantly inhibited the viability of TNBC cell lines, with IC50 values ranging from 0.3 to 2.8 μmol/L.
Exhibited weaker inhibitory effects on HER2+ SKBR3, (IC50 ~ 16 μM) and ER+MCF7, (IC50 > 20 μM) breast cancer cell lines.
Showed no toxicity against normal breast epithelial MCF10A cells.
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Cell Line:HCC-70 cells
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Concentration:20 μM
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Incubation Time:20 h
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Result:Reduced Notch2 receptor protein levels.
Inhibited the phosphorylation of mTOR, STAT3, and NF-κB, and increased the level of cleaved caspase-3, a marker of apoptosis.
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Cell Line:MDA-MB-231 cells, BT-549 cells
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Concentration:20 μM
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Incubation Time:20 h
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Result:Significantly reduced STAT3 and NF-κB reporter activity in TNBC cells that stably express these reporters.
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Cell Line:MDA-MB-231 cells, BT-549 cells, MCF10A cells
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Concentration:20 μM
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Incubation Time:24 h
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Result:Induced apoptosis in TNBC cells, but not in normal mammary epithelial cells.
Parmacokinetics
| Species | Dose | Route | Tmax | Cmax | AUCinf | T1/2 | CL/F |
|---|---|---|---|---|---|---|---|
| Rat | 10 mg/kg | i.p. | 0.54 h | 6271 ng/mL | 5233 ng·h/mL | 0.52 h | 1971 mL/h/kg |
In Vivo
HBS-101 (10 mg/kg, i.p.) can be rapidly absorbed and effectively penetrates the blood-brain barrier in mice[1].
HBS-101 (2-10 mg/kg, p.o., 5 days) doses up to 10 mg/kg (oral) for 5 consecutive days are safe and do not produce observable organ toxicity in mice[1].
HBS-101 (2 mg/kg, 5 mg/kg, p.o., 5 days) effectively inhibits the growth of TNBC orthotopic tumors with oral administration, and 5 mg/kg is determined to be the minimum effective dose in mice[1].
HBS-101 (5 mg/kg, p.o., 5 days a week) reduces the proliferative activity of tumors in MDA-MB-231 cells xenograft mice[1].
HBS-101 (10 mg/kg, i.p., 5 days a week) exhibits potent anti-tumor activity in a brain metastasis model in mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Rats[1].
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Dosage:1 mg/kg, 10 mg/kg
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Administration:I.v., p.o.
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Result:Had monoexponential disposition in vivo and had an estimated plasma half-life between 0.7 and 1.6 hours.
Had excellent oral bioavailability in rats.
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Animal Model:Female C57BL/6 mice[1].
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Dosage:10 mg/kg
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Administration:I.p., once
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Result:Absorbed rapidly following i.p. administration, resembling an i.v. bolus drug administration.
Detected in the brain, with peak detectable levels reaching 1,654 ng/g 10 minutes after administration, suggesting that HBS-101 effectively crosses the blood-brain barrier.
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Animal Model:Female C57BL/6 mice[1].
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Dosage:2 mg/kg, 5 mg/kg, 10 mg/kg
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Administration:P.o., 5 days
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Result:No abnormalities were detected during the gross pathological examination of the animals.
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Animal Model:MDA-MB-231 cells (2 × 106) mixed with a 1:1 volume of Matrigel were injected into the mammary fat pad of the nude mice[1].
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Dosage:2 mg/kg, 5 mg/kg
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Administration:P.o., 5 times a week
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Result:Led to a significant dose-dependent reduction in tumor volume.
Not affected mouse body weight.
Significant decreased in Ki-67–positive cells.
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Animal Model:Female SCID mice were used as recipients for 2 mm3 TNBC–PDX-96 tumor tissue implants to establish subcutaneous PDX tumor models[1].
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Dosage:5 mg/kg
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Administration:P.o., 5 times a week
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Result:Significantly inhibited PDX tumor growth, with tumor volume and weight significantly reduced. Significant decrease in Ki-67-positive cells.
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Animal Model:1.75 × 105 brain-metastatic MDA-MB-231-BrM2-831 cells were orthotopically injected into the right cerebral hemisphere of female NOD.CB17-Prkdcscid/NCrCrl mice[1].
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Dosage:10 mg/kg
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Administration:I.p., 5 times a week
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Result:Significantly reduced tumor progression and extended the survival of mice with orthotopic tumors.
Chemical Information
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Appearance Solid
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Peso molecular 346.41
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Fòrmula C21H24F2O2
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Color White to off-white
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SMILES
C[C@@]12[C@](O)(C(F)(F)C#C)CC[C@@]1([H])[C@]3([H])CCC4=CC(CCC4=C3CC2)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
In Vitro:
DMSO : 100 mg/mL (288.68 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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.
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.
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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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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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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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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CCK-8/WST-8 Cell Proliferation Assay
The CCK-8/WST-8 assay is based on the reduction of the water-soluble tetrazolium salt WST-8 to a water-soluble formazan product by cellular dehydrogenases in metabolically active cells, where the generated formazan amount is proportional to the number of living cells and is quantified by measuring absorbance in the visible range, providing a colorimetric readout for cell viability and proliferation assessment. This class of tetrazolium-based assays improves upon earlier MTT-based systems by producing a water-soluble formazan, eliminating the need for organic solubilization steps and enabling direct spectrophotometric measurement in culture medium.
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Research Protocol for Inflammation-related Diseases
The NLRP3 inflammasome is a cytosolic innate immune signaling platform that integrates priming signals and danger-signal activation to promote caspase-1 activation, maturation of IL-1β and IL-18, and gasdermin D-mediated pyroptotic cell death. The core experimental logic is to determine whether inflammatory disease phenotypes are driven by increased NLRP3 expression, ASC-containing inflammasome assembly, caspase-1 cleavage, GSDMD cleavage, and extracellular release of IL-1β/IL-18 rather than by nonspecific cell injury alone. The pathway is strongly linked to inflammation-related disease phenotypes because monosodium urate crystals activate NALP3/NLRP3 inflammasome signaling in gout-like crystal inflammation, cholesterol crystals activate NLRP3 inflammasomes in atherogenesis models, and DSS-induced intestinal inflammation has been reported to involve NLRP3 inflammasome activity. However, experimental colitis studies also show context-dependent protective effects of NLRP3 inflammasome co
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MTT Cell Proliferation Assay
The MTT assay is a colorimetric endpoint assay for estimating viable cell number, cell growth, cytotoxicity, or cell activation in cultured mammalian cells. Living cells reduce the yellow tetrazolium salt MTT into purple/blue formazan, while dead cells do not generate the same signal; the resulting color can be quantified with a multiwell spectrophotometer. MTT reduction is commonly interpreted as a readout of metabolic activity that often correlates with viable cell number, but it should not be treated as a direct cell-counting method unless the assay is optimized for the cell type and experimental condition. Studies show that MTT reduction can involve mitochondrial and non-mitochondrial reducing systems, and formazan may accumulate in intracellular lipid droplets rather than simply marking mitochondria.
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Colony Formation (Clonogenic) Assay
The clonogenic (colony formation) assay measures the ability of a single cell to retain reproductive viability and form a macroscopic colony, typically defined as a cluster derived from one progenitor cell after a defined growth period. This assay is widely used to evaluate cell survival after exposure to ionizing radiation or cytotoxic treatments and is considered a standard method in radiation biology for generating dose-response relationships of reproductive cell death. Colony formation reflects long-term proliferative capacity rather than short-term metabolic activity, and survival is quantified by comparing treated versus untreated conditions based on colony number and derived survival fractions.
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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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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.
Pureza y Documentación
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Ficha de datos (285 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
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. 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 |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.8868 mL | 14.4338 mL | 28.8675 mL | 72.1688 mL |
| 5 mM | 0.5774 mL | 2.8868 mL | 5.7735 mL | 14.4338 mL | |
| 10 mM | 0.2887 mL | 1.4434 mL | 2.8868 mL | 7.2169 mL | |
| 15 mM | 0.1925 mL | 0.9623 mL | 1.9245 mL | 4.8113 mL | |
| 20 mM | 0.1443 mL | 0.7217 mL | 1.4434 mL | 3.6084 mL | |
| 25 mM | 0.1155 mL | 0.5774 mL | 1.1547 mL | 2.8868 mL | |
| 30 mM | 0.0962 mL | 0.4811 mL | 0.9623 mL | 2.4056 mL | |
| 40 mM | 0.0722 mL | 0.3608 mL | 0.7217 mL | 1.8042 mL | |
| 50 mM | 0.0577 mL | 0.2887 mL | 0.5774 mL | 1.4434 mL | |
| 60 mM | 0.0481 mL | 0.2406 mL | 0.4811 mL | 1.2028 mL | |
| 80 mM | 0.0361 mL | 0.1804 mL | 0.3608 mL | 0.9021 mL | |
| 100 mM | 0.0289 mL | 0.1443 mL | 0.2887 mL | 0.7217 mL |
HBS-101 Related Classifications
HY-178164 Related Classifications
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