BOLD-100 (Synonyms: NKP-1339 free base; IT-139 free base; KP-1339 free base) |
| رقم الكتالوجGC65318 |
بولد-100 هو عامل مضاد للسرطان يعتمد على الروثينيوم. كما أن بولد-100 هو مثبط لزيادة تعبير GRP78 المحفزة بالإجهاد، والذي يخلق اضطرابًا في استقرار الغشاء البلازمي للأورام (ER) ويؤدي إلى زيادة التوتر في ER واستجابة فائض البروتينات (UPR). يتداخل بولد-100 مع التفاعل المعقَّد بين استجابة التوتر في ER، دوران الأكسية، وتنفذ تشغيلية.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 783324-98-1
Sample solution is provided at 25 µL, 10mM.
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BOLD-100 is a ruthenium-based anticancer agent[1]. BOLD-100 has high tumor targeting potential, strongly binds to serum proteins such as albumin and transferrin, and is activated in the reducing tumor environment[2]. BOLD-100 can disrupt endoplasmic reticulum (ER) homeostasis and induce ER stress and unfolded protein response (UPR)[3].
In vitro, BOLD-100 (100μM) treatment of MCF7(2) cells for 72h significantly reduced S phase cells, increased G2/M phase cells, significantly reduced cell cycle proteins (such as RAD51, PCNA, ATM), and induced an increase in intracellular reactive oxygen species (ROS)[4]. BOLD-100 (100μM) treatment of HCT116 cells for 24h enhanced the phosphorylation of eIF2A serine 51 in cells, but reduced the expression of the basal ER chaperone GRP78[5]. BOLD-100 (0-200μM) has a significant inhibitory effect on malignant cell lines from various sources, such as liver cancer, melanoma, lung cancer and colon cancer, when treated for 72h, with an IC50 value of 45-200μM[6].
In vivo, BOLD-100 (30mg/kg) was treated by intravenous injection for 2 weeks in mice with Hep3B cell xenografts, which significantly inhibited the growth of transplanted tumors in mice, improved the survival rate of mice, and increased the number of apoptotic cells in tumor tissues. It has a synergistic therapeutic effect with sorafenib[6]. BOLD-100 (50mg/kg) was treated by intravenous injection for 3 weeks in mice with VACO432 cell xenografts, but the inhibitory effect on tumor growth was not obvious. Combined treatment with AZD6738 can lead to a slowdown in tumor growth, but the tolerance is poor and the mice lose weight[7].
References:
[1] Swaminathan S, Haribabu J, Karvembu R. From Concept to Cure: The Road Ahead for Ruthenium‐Based Anticancer Drugs[J]. ChemMedChem, 2024, 19(23): e202400435.
[2] Happl B, Brandt M, Balber T, et al. Synthesis and Preclinical Evaluation of Radiolabeled [103Ru] BOLD-100[J]. Pharmaceutics, 2023, 15(11): 2626.
[3] Ranzato E, Bonsignore G, Martinotti S. ER stress response and induction of apoptosis in malignant pleural mesothelioma: The Achilles heel targeted by the anticancer ruthenium drug BOLD-100[J]. Cancers, 2022, 14(17): 4126.
[4] Bakewell S, Conde I, Fallah Y, et al. Inhibition of DNA repair pathways and induction of ROS are potential mechanisms of action of the small molecule inhibitor BOLD-100 in breast cancer[J]. Cancers, 2020, 12(9): 2647.
[5] Baier D, Schoenhacker-Alte B, Rusz M, et al. The anticancer ruthenium compound BOLD-100 targets glycolysis and generates a metabolic vulnerability towards glucose deprivation[J]. Pharmaceutics, 2022, 14(2): 238.
[6] Heffeter P, Atil B, Kryeziu K, et al. The ruthenium compound KP1339 potentiates the anticancer activity of sorafenib in vitro and in vivo[J]. European Journal of Cancer, 2013, 49(15): 3366-3375.
[7] Griffin D, Carson R, Moss D, et al. Ruthenium Drug BOLD-100 Regulates BRAF MT Colorectal Cancer Cell Apoptosis through AhR/ROS/ATR Signaling Axis Modulation[J]. Molecular Cancer Research, 2024, 22(12): 1088-1101.
| Cell experiment [1]: | |
Cell lines | MCF7(2) cells (MCF7(2) is a MCF7 derivative cell line that shows increased sensitivity to estrogen) |
Preparation Method | Cells were grown at 70% confluence on 100mm in complete growth medium for 24h. The following day, cells were treated with vehicle or 100μM BOLD-100 for an additional 72h. Cells were then fixed in ethanol, and analyzed by the Flow Cytometry. Each experiment was repeated at least three times. |
Reaction Conditions | 100μM; 72h |
Applications | Treatment of MCF7(2) cells with BOLD-100 significantly reduced the S phase and increased the G2/M phase compared with cells treated with the vehicle. |
| Animal experiment [2]: | |
Animal models | Balb/c SCID mice |
Preparation Method | Hep3B xenografts were grown in Balb/c SCID mice and treated with BOLD-100 (30mg/kg; i.v.; once a week) and/or Sorafenib (25mg/kg; orally; five days a week) for 2 weeks when tumor nodules reached an average size of 25mm3. Tumour size was assessed by caliper measurement. |
Dosage form | 30mg/kg; once a week for 2 weeks; i.v. |
Applications | Withregardto the anticancer activity, BOLD-100 as well as Sorafenib monotreatment induced a distinct delay in tumour growth. |
References: | |
| Cas No. | 783324-98-1 | SDF | |
| المرادفات | NKP-1339 free base; IT-139 free base; KP-1339 free base | ||
| Formula | C14H12Cl4N4Ru | M.Wt | 479.15 |
| الذوبان | Storage | Store at -20°C | |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.087 mL | 10.4351 mL | 20.8703 mL |
| 5 mM | 0.4174 mL | 2.087 mL | 4.1741 mL |
| 10 mM | 0.2087 mL | 1.0435 mL | 2.087 mL |
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Quality Control & SDS
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- Purity: >98.00%
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