| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
MMP-2, MMP-3, MMP-9
Inhibitor constants (Ki): 11 nM for MMP-2, 134 nM for MMP-3, 301 nM for MMP-9 [3] |
|---|---|
| ln Vitro |
Without influencing cell proliferation, tanomastat (BAY 12-9566) (1-10000 nM; 6 hours) inhibits endothelial cell matrix invasion in a concentration-dependent manner (IC50=840 nM) [2]. Renal tubule development is fully inhibited by tanomastat (BAY 12-9566) at concentrations of 1–00 µM for five days [3].
At concentrations ranging from 10 µM to 1 mM, BAY 12-9566 did not significantly inhibit the proliferation of MDA-MB-435 human breast cancer cells or HUVEC cells after 48, 72, and 120 hours of incubation. [3] - In a microcarrier (MC) assay, BAY 12-9566 at concentrations of 15 to 100 µM completely inhibited tubule formation by HUVEC cells cultured within a fibrin gel. At concentrations up to 10 µM, no inhibition of tubule formation was observed. [3] |
| ln Vivo |
Tanomastat (BAY 12-9566) (100 mg/kg; oral; once daily for 7 weeks) reduces the quantity and size of lung metastases while also inhibiting local tumor regrowth without having any harmful side effects [3].
In an orthotopic MDA-MB-435 human breast cancer xenograft model in athymic nude mice, daily oral administration of BAY 12-9566 at 100 mg/kg/day for 7 weeks (post-resection of the primary tumor) inhibited local tumor regrowth volume by 58% compared to the vehicle control group (P = 0.04). [3] - In the same model, treatment with BAY 12-9566 decreased the number of pulmonary metastases by 57% (8.8 ± 2.9 in treated vs. 20.8 ± 6.9 in control) and the volume of pulmonary metastases by 88% (3.4 ± 1.2 mm³ in treated vs. 28.7 ± 13.6 mm³ in control) compared to the control group. [3] - The antitumor effects correlated with serum concentrations of BAY 12-9566. At serum concentrations >6 µg/mL, tumor regrowth volume was inhibited by 78%, the number of metastases by 76%, and the volume of metastases by 92%. [3] - Gelatin zymography of sera and regrowth tumor tissue from treated mice showed reduced MMP-9 activity compared to controls, while MMP-2 activity levels were similar between the two groups. [3] |
| Cell Assay |
Cell Proliferation Assay: MDA-MB-435 human breast cancer cells and HUVEC cells were seeded at 5 × 10³ cells per well in 96-well plates and incubated with various concentrations of BAY 12-9566 (ranging from 10 µM to 1 mM). After 48, 72, and 120 hours, a combined tetrazolium/phenazine methosulfate solution was added to the wells. Following a 60-minute incubation, absorbance at 450 nm was measured to assess cell proliferation. [3]
- Microcarrier (MC) Assay for Angiogenesis: HUVEC cells were added to gelatin-coated Cytodex 3 microcarriers (MCs) at a final concentration of 30 cells per MC and incubated for four days. The cell-coated MCs were then embedded in a fibrinogen solution (2.5 mg/mL) clotted with thrombin (0.625 U/mL). After gel equilibration, fresh medium containing vascular endothelial growth factor (100 ng/mL), basic fibroblast growth factor (30 ng/mL), and various doses of BAY 12-9566 (1, 10, 15, 20, and 100 µM) was added. The number of tubules formed was determined five days after gel polymerization. [3] |
| Animal Protocol |
Animal/Disease Models: Six to eightweeks old female BALB/c nude mice (carrying MDA-MB-435 cells) [3]
Doses: 100 mg/kg Route of Administration: Oral; one time/day for 7 weeks Experimental Results: Inhibition of local tumor regeneration 58%, without causing any toxic effects, and inhibited the number and volume of lung metastases by 57% and 88%, respectively. Orthotopic Human Breast Cancer Xenograft Model:** Female BALB/c nude mice (6-8 weeks old) were injected with 5 × 10⁵ MDA-MB-435 cells into the mammary fat pad. Eight weeks post-implantation, the primary tumors were surgically resected under anesthesia. After surgery, BAY 12-9566, suspended in a vehicle of 0.5% sodium carboxymethylcellulose and 0.2% Tween 80, was administered orally once daily at a dose of 100 mg/kg/day for 7 weeks until the study was terminated. Control mice received the vehicle only. [3] Orthotopic Human Breast Cancer Xenograft Model: Female BALB/c nude mice (6-8 weeks old) were injected with 5 × 10⁵ MDA-MB-435 cells into the mammary fat pad. Eight weeks post-implantation, the primary tumors were surgically resected under anesthesia. After surgery, BAY 12-9566, suspended in a vehicle of 0.5% sodium carboxymethylcellulose and 0.2% Tween 80, was administered orally once daily at a dose of 100 mg/kg/day for 7 weeks until the study was terminated. Control mice received the vehicle only. [3] |
| ADME/Pharmacokinetics |
Serum Concentration Analysis: Serum concentrations of BAY 12-9566 in mice were determined using a reversed-phase HPLC-UV assay. Serum samples were prepared via ethyl acetate extraction, followed by evaporation and reconstitution in mobile phase. The analysis used a gradient elution with varying mixtures of 1% acetic acid and acetonitrile, and UV detection at 290 nm. The retention time for BAY 12-9566 was 7.4 minutes. [3]
|
| Toxicity/Toxicokinetics |
Daily oral administration of BAY 12-9566 at 100 mg/kg/day over a 7-week period did not affect the body weight of the mice, indicating no overt toxic effects from the treatment. [3]
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| References | |
| Additional Infomation |
Tanomastat is an organochlorine compound belonging to the biphenyl class. Tanomastat is a biphenyl matrix metalloproteinase (MMP) inhibitor (MMPI) with potential antitumor activity. Tanomastat inhibits MMP-2, MMP-3, and MMP-9, thereby inhibiting extracellular matrix degradation and potentially inhibiting angiogenesis, tumor growth, invasion, and metastasis. MMPs contain at least 18 zinc-containing endopeptides capable of degrading collagen and proteoglycans. Drug Indications It has been investigated for the treatment of pancreatic cancer, lung cancer, ovarian cancer, and osteoarthritis.
BAY 12-9566 is a novel, non-peptidic biphenyl matrix metalloproteinase inhibitor that is orally bioavailable. [3] - It demonstrated nanomolar inhibitory activity against several MMPs. [3] - Although all clinical trials in cancer involving BAY 12-9566 have been halted, this MMP inhibitor has never been used in clinical trials in breast cancer. The results from this study suggest it may be a useful and safe oral treatment adjunctive to surgery for breast cancer. [3] |
| Molecular Formula |
C23H19O3SCL
|
|---|---|
| Molecular Weight |
410.91316
|
| Exact Mass |
410.074
|
| CAS # |
179545-77-8
|
| Related CAS # |
(Rac)-Tanomastat;179545-76-7
|
| PubChem CID |
6918336
|
| Appearance |
White to off-white solid powder
|
| Density |
1.33g/cm3
|
| Boiling Point |
620.1ºC at 760 mmHg
|
| Melting Point |
110-110.5ºC
|
| Flash Point |
328.8ºC
|
| Vapour Pressure |
3.07E-16mmHg at 25°C
|
| Index of Refraction |
1.662
|
| LogP |
6.072
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
28
|
| Complexity |
504
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C1=CC=C(C=C1)SC[C@@H](CC(=O)C2=CC=C(C=C2)C3=CC=C(C=C3)Cl)C(=O)O
|
| InChi Key |
JXAGDPXECXQWBC-LJQANCHMSA-N
|
| InChi Code |
InChI=1S/C23H19ClO3S/c24-20-12-10-17(11-13-20)16-6-8-18(9-7-16)22(25)14-19(23(26)27)15-28-21-4-2-1-3-5-21/h1-13,19H,14-15H2,(H,26,27)/t19-/m1/s1
|
| Chemical Name |
(2S)-4-[4-(4-chlorophenyl)phenyl]-4-oxo-2-(phenylsulfanylmethyl)butanoic acid
|
| 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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 2.4336 mL | 12.1681 mL | 24.3362 mL | |
| 5 mM | 0.4867 mL | 2.4336 mL | 4.8672 mL | |
| 10 mM | 0.2434 mL | 1.2168 mL | 2.4336 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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