| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
Cambinol (formerly NSC-112546) is a potent SIRT (silent information regulator enzymes) inhibitor with IC50 values of 56 and 59 μM for SIRT1 and SIRT2, respectively. It inhibits NAD-dependent deacetylase activity of human SIRT1 and SIRT2. Inhibition of SIRT1 activity with cambinol during genotoxic stress leads to hyperacetylation of key stress response proteins and promotes cell cycle arrest. Treatment of BCL6-expressing Burkitt lymphoma cells with cambinol as a single agent induced apoptosis, which was accompanied by hyperacetylation of BCL6 and p53. Because acetylation inactivates BCL6 and has the opposite effect on the function of p53 and other checkpoint pathways, the antitumor activity of cambinol in Burkitt lymphoma cells may be accomplished through a combined effect of BCL6 inactivation and checkpoint activation. Cambinol was well tolerated in mice and inhibited growth of Burkitt lymphoma xenografts.
| Targets |
Human SIRT1 (silent information regulator 2 enzyme): NAD-dependent deacetylase activity is inhibited by Cambinol [1]
- Human SIRT2 (silent information regulator 2 enzyme): NAD-dependent deacetylase activity is inhibited by Cambinol [1] |
|---|---|
| ln Vitro |
Human SIRT1 and SIRT2 NAD-dependent deacetylase activity is inhibited by cambinol. Using Cambinol to inhibit SIRT1 activity during genotoxic stress causes important stress response proteins to become hyperacetylated, which in turn encourages cell cycle arrest. When cambinol is used alone to treat BCL6-expressing Burkitt lymphoma cells, it causes apoptosis along with hyperacetylation of p53 and BCL6. Cambinol exhibits no action against SIRT3 and only modest inhibition of SIRT5 (42% inhibition at 300 μM) [1].
1. Inhibition of SIRT1 and SIRT2 deacetylase activity: Cambinol acts as a small-molecule inhibitor that specifically targets the NAD-dependent deacetylase activity of human SIRT1 and SIRT2. When cells are exposed to genotoxic stress, treatment with Cambinol leads to hyperacetylation of key stress response proteins, which is a direct consequence of SIRT1 and SIRT2 inhibition [1] 2. Induction of apoptosis in Burkitt lymphoma cells: In Burkitt lymphoma cells that express BCL6, Cambinol as a single agent effectively induces apoptosis. This apoptotic effect is accompanied by hyperacetylation of both BCL6 and p53 proteins. Acetylation inactivates the oncoprotein BCL6 while activating p53 and other checkpoint pathways, and this combined effect is believed to be responsible for the antitumor activity of Cambinol in these cells [1] 3. Promotion of cell cycle arrest: Under genotoxic stress conditions, inhibition of SIRT1 activity by Cambinol results in the hyperacetylation of stress response proteins, which in turn triggers cell cycle arrest. This cell cycle arrest likely contributes to the drug's ability to suppress tumor cell proliferation [1] |
| ln Vivo |
In mice, camebinol (100 mg/kg) is well tolerated and suppresses the growth of xenografts with Burkitt lymphoma. Animals treated with cambinol do not significantly lose weight in comparison to controls. Novel anticancer drugs could be NAD-dependent deacetylase inhibitors[1].
1. Antitumor activity in Burkitt lymphoma xenografts: Cambinol exhibits significant antitumor efficacy in mice bearing Burkitt lymphoma xenografts. Treatment with Cambinol leads to inhibition of tumor growth, demonstrating its in vivo effectiveness against this type of cancer [1] 2. Good tolerability in mice: Cambinol is well tolerated by mice during the treatment period, with no obvious adverse effects reported that would limit its use. This favorable tolerability profile supports its potential as an anticancer agent [1] |
| Enzyme Assay |
1. NAD-dependent deacetylase activity assay for SIRT1 and SIRT2: Recombinant human SIRT1 and SIRT2 enzymes are prepared and incubated with appropriate substrates that contain acetylated residues, along with NAD+ as a cofactor. Different concentrations of Cambinol are added to the reaction mixture, and the mixture is incubated under specific conditions (temperature, time) to allow the deacetylation reaction to proceed. After incubation, the reaction is terminated, and the level of deacetylation is detected using a suitable method (e.g., immunodetection with antibodies specific to acetylated substrates or fluorescence-based detection). The deacetylase activity of SIRT1 and SIRT2 in the presence of Cambinol is compared to that in the absence of the inhibitor (control group) to determine the inhibitory effect of Cambinol on the enzymes [1]
|
| Cell Assay |
1. Apoptosis assay in Burkitt lymphoma cells: Burkitt lymphoma cells expressing BCL6 are seeded in cell culture plates and allowed to adhere or grow in suspension. The cells are then treated with Cambinol at various concentrations as a single agent, with a control group treated with a solvent (e.g., DMSO). After a specific incubation period, the cells are harvested and analyzed for apoptotic markers. This includes detecting hyperacetylation of BCL6 and p53 using Western blot analysis with specific antibodies against acetylated forms of these proteins. Additionally, apoptotic cell death is assessed using methods such as flow cytometry (e.g., Annexin V/PI staining) or detection of caspase activation to quantify the proportion of apoptotic cells [1]
2. Cell cycle arrest assay under genotoxic stress: Tumor cells are seeded in culture plates and subjected to genotoxic stress (e.g., exposure to DNA-damaging agents or radiation). Simultaneously or sequentially, the cells are treated with Cambinol at a predetermined concentration. After incubation, the cells are collected, fixed, and stained with a DNA-binding dye (e.g., propidium iodide). Flow cytometry is then used to analyze the cell cycle distribution, determining the proportion of cells in G0/G1, S, and G2/M phases. The presence of cell cycle arrest is indicated by a significant increase in the number of cells in a specific phase compared to the control group (genotoxic stress alone without Cambinol) [1] 3. Western blot analysis for hyperacetylation of stress response proteins: Cells are treated with Cambinol under genotoxic stress conditions. After treatment, the cells are lysed to extract total proteins, which are then separated by SDS-PAGE and transferred to a membrane. The membrane is probed with specific antibodies that recognize acetylated forms of key stress response proteins (e.g., p53, BCL6). The corresponding total proteins are also detected as loading controls. The intensity of the bands corresponding to acetylated proteins is quantified using imaging software, and the level of hyperacetylation in Cambinol-treated cells is compared to that in control cells [1] |
| Animal Protocol |
100 mg/kg cambinol was the highest dose that could be administered as a single i.v. injection
Daudi Burkitt lymphoma cells (20 × 106) resuspended in PBS were administered s.c. into the flank of 6- to 8-week-old nonobese diabetic/severe combined immunodeficient male mice. 1. Burkitt lymphoma xenograft model in mice: Immunodeficient mice (suitable for xenograft studies) are selected and subcutaneously inoculated with Burkitt lymphoma cells to establish tumor xenografts. Once the tumors reach a predetermined size (e.g., a specific volume or diameter), the mice are randomly divided into treatment and control groups. Cambinol is formulated in an appropriate solvent or vehicle (e.g., DMSO combined with a carrier such as corn oil) to ensure solubility and bioavailability. The treatment group receives Cambinol via a specific administration route (not explicitly stated in the literature, but common routes include intraperitoneal injection or oral gavage) at a predetermined dose and frequency (e.g., daily or every other day) for a specified treatment period. The control group receives the same volume of the solvent/vehicle without Cambinol. During the treatment period, the mice are monitored for general health status, and tumor sizes are measured regularly (e.g., every 2-3 days) using calipers to calculate tumor volume. At the end of the treatment period, the mice are euthanized, and the tumors are excised, weighed, and further analyzed if necessary to evaluate the antitumor effect of Cambinol [1] |
| References | |
| Additional Infomation |
Cambino is a β-naphthol derivative that reduces cellular survival under stress by inhibiting NAD-dependent deacetylases. Its potential as a cancer treatment is currently being investigated. Mechanism of Action Cambino inhibits the NAD-dependent deacetylases SIRT1 and SIRT2, which belong to the sirtuins protein family. Inhibition of SIRT1 and SIRT2 in stressed cells increases the acetylation levels of p53, Ku70, and Foxo3a. This inhibition makes cells more sensitive to drugs such as etoposide and paclitaxel (not just other DNA-damaging drugs). While the mechanism of this sensitization is not fully understood, it is independent of p53, Ku70, or Foxo3a. This independent mechanism suggests the existence of additional molecular targets. Cambino is non-competitive for NAD but competitive for the SIRT2 substrate H-4 peptide. Inhibition of SIRT2 increases the acetylation levels of tubulin. Cambinol can also increase the acetylation level of BCL6, a protein essential for tumorigenesis. Cambinol is also a weak inhibitor of SIRT5.
1. Mechanism of antitumor action: The antitumor activity of Cambinol is thought to be achieved through a dual mechanism. First, it inhibits SIRT1 and SIRT2, leading to excessive acetylation of BCL6, thereby inactivating this oncoprotein. Second, excessive acetylation of p53 and other checkpoint pathway proteins activates these tumor suppressor pathways. The combined effect of BCL6 inactivation and checkpoint pathway activation can induce tumor cell apoptosis and cell cycle arrest, thereby exerting an antitumor effect [1] 2. Anticancer potential: As a small molecule inhibitor of SIRT1 and SIRT2, Cambinol represents a new class of potential anticancer drugs. Its ability to inhibit tumor growth in xenograft models and its good tolerability in mice support its further development and evaluation in cancer treatment, especially Burkitt lymphoma and other cancers in which SIRT1/SIRT2 or BCL6 plays an important role in tumorigenesis [1] |
| Molecular Formula |
C21H16N2O2S
|
|
|---|---|---|
| Molecular Weight |
360.43
|
|
| Exact Mass |
360.093
|
|
| CAS # |
14513-15-6
|
|
| Related CAS # |
|
|
| PubChem CID |
3246390
|
|
| Appearance |
White to off-white solid powder
|
|
| Density |
1.4±0.1 g/cm3
|
|
| Boiling Point |
667ºC at 760mmHg
|
|
| Melting Point |
235 °C(dec.)
|
|
| Flash Point |
357.2ºC
|
|
| Vapour Pressure |
2.12E-18mmHg at 25°C
|
|
| Index of Refraction |
1.771
|
|
| LogP |
4.71
|
|
| Hydrogen Bond Donor Count |
3
|
|
| Hydrogen Bond Acceptor Count |
3
|
|
| Rotatable Bond Count |
3
|
|
| Heavy Atom Count |
26
|
|
| Complexity |
597
|
|
| Defined Atom Stereocenter Count |
0
|
|
| InChi Key |
RVNSQVIUFZVNAU-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C21H16N2O2S/c24-18-11-10-13-6-4-5-9-15(13)16(18)12-17-19(14-7-2-1-3-8-14)22-21(26)23-20(17)25/h1-11,24H,12H2,(H2,22,23,25,26)
|
|
| Chemical Name |
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.77 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7745 mL | 13.8723 mL | 27.7446 mL | |
| 5 mM | 0.5549 mL | 2.7745 mL | 5.5489 mL | |
| 10 mM | 0.2774 mL | 1.3872 mL | 2.7745 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.
Sirtuin inhibitors.A,structure of splitomicin, cambinol (NSC-112546), and ADS012.B,cambinol inhibits human SIRT1 (IC50, 56 ± 2 μmol/L) and SIRT2 (IC50, 59 ± 4) NAD-dependent deacetylation of acetyl-histone H4 peptide.Cancer Res.2006 Apr 15;66(8):4368-77. |
|---|
Cambinol induces hyperacetylation of SIRT1 and SIRT2 substrates p53 and tubulin.Cancer Res.2006 Apr 15;66(8):4368-77. |
Inhibition of SIRT1 with cambinol sensitizes NCI H460 lung cancer cells to etoposide and paclitaxel and enhances etoposide-induced G2arrest.Cancer Res.2006 Apr 15;66(8):4368-77. |
Cambinol sensitizes cells to chemotherapeutic agents in a p53-independent manner.Cancer Res.2006 Apr 15;66(8):4368-77. |
|---|
Cambinol is active as a single agent in Burkitt lymphoma cell lines.Cancer Res.2006 Apr 15;66(8):4368-77. |
Cambinol induces hyperacetylation of p53 and BCL6 and interferes with BCL6 transcriptional repression.Cancer Res.2006 Apr 15;66(8):4368-77. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
