| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Cathepsins B, L, S, and V (The probe L-217, synthesized using BMV109 as the quencher, showed inhibitory activity against these enzymes. Ki values for L-217 are reported: Cathepsin B (Ki = 0.1 nM), Cathepsin L (Ki = 0.5 nM), Cathepsin S (Ki = 0.7 nM), Cathepsin V (Ki = 0.1 nM). Note: These Ki values are for the probe L-217, not BMV109 itself. The paper states BMV109 is a potent pan-cathepsin inhibitor but does not provide specific IC50/Ki values for BMV109 alone). [1]
|
|---|---|
| ln Vitro |
BMV109 was used as a key component (quencher) in synthesizing a quenched fluorescent activity-based probe (ABP) L-217 targeting cathepsins. The probe itself (BMV109 conjugated to Cy5) demonstrated target engagement and enzymatic activity-dependent activation in vitro. [1]
Probe L-217 (BMV109-Cy5 conjugate) effectively labeled active cathepsins in cell lysates from various cancer cell lines (e.g., MDA-MB-231 breast cancer cells). Labeling intensity correlated with enzyme activity levels. [1] Pre-incubation of cell lysates with the broad-spectrum cathepsin inhibitor JPM-OEt (which shares the same warhead as BMV109) blocked L-217 labeling, confirming specificity for active cathepsins. [1] Probe L-217 (BMV109-Cy5 conjugate) was used to detect active cathepsins in fresh frozen human colon cancer tissue sections ex vivo. Strong fluorescence signal was observed in tumor regions compared to adjacent normal tissue. [2] In live RAW cells, BMV109 (Compound 8; 0.05 µM, 0.1 µM, 0.5 µM, 1 µM, and 5 µM) identifies all target cysteine cathepsins (B, S, L, and X) equally [1]. |
| ln Vivo |
Probe L-217 (BMV109-Cy5 conjugate) was administered intravenously (IV) to mice bearing MDA-MB-231 breast cancer xenografts. In vivo fluorescence imaging showed specific accumulation and activation of the probe within tumors over time, with peak tumor-to-background ratio achieved at 24 hours post-injection. Signal was significantly reduced in mice pre-treated with JPM-OEt, confirming specificity. [1]
BMV109 itself was used as a pre-injection blocking agent (IV, 100 nmol, 1 hour prior to L-217) in mice bearing MDA-MB-231 xenografts. Pre-treatment with BMV109 significantly reduced the subsequent tumor fluorescence signal from the L-217 probe compared to saline pre-treated controls, demonstrating in vivo target engagement and inhibition by BMV109. [1] Probe L-217 (BMV109-Cy5 conjugate) was administered intravenously to patients with suspected or confirmed colorectal cancer undergoing surgery. Fluorescence endoscopy using a clinical wide-field device successfully detected elevated cathepsin activity in colorectal cancer lesions compared to adjacent normal mucosa in human patients in vivo. This demonstrates the translational application of the probe derived from BMV109. [2] In breast cancer mice models, BMV109 (compound 8; 20 nmol; intravenous administration) produces tumor-specific fluorescence signals[1]. |
| Enzyme Assay |
The inhibitory constant (Ki) of the synthesized probe L-217 (BMV109-Cy5 conjugate) against recombinant human cathepsins B, L, S, and V was determined using continuous enzymatic assays. Enzymes were pre-incubated with varying concentrations of L-217 for 30 minutes at room temperature before adding the fluorogenic substrate. Residual enzyme activity was measured kinetically using a fluorescence plate reader. Ki values were calculated from the dose-response curves using standard methods for tight-binding inhibitors. [1]
Specificity profiling of the probe L-217 (BMV109-Cy5 conjugate) against a panel of other recombinant proteases (e.g., caspases, legumain, proteasome) was performed using similar enzymatic activity assays with appropriate fluorogenic substrates to confirm selectivity towards cathepsins. [1] |
| Cell Assay |
For labeling active cathepsins in cultured cells, cancer cell lines (e.g., MDA-MB-231) were lysed. Cell lysates were incubated with the probe L-217 (BMV109-Cy5 conjugate) at a specific concentration for a defined period (e.g., 1 hour at 37°C).
To confirm labeling specificity, lysates were pre-incubated with a broad-spectrum cathepsin inhibitor (JPM-OEt) for 30 minutes prior to adding L-217. After incubation, the reaction was stopped, and proteins were separated by SDS-PAGE under non-reducing conditions. The labeled cathepsins were visualized directly in the gel using a fluorescence scanner specific for the Cy5 fluorophore. Band intensity indicated the amount of active enzyme present. [1] For ex vivo tissue imaging, fresh frozen human colon cancer tissue sections were cut. Tissue sections were incubated with the probe L-217 (BMV109-Cy5 conjugate) in buffer for a set time (e.g., 1 hour at 37°C). Sections were then washed, fixed, counterstained with DAPI for nuclei, and mounted. Fluorescence images (Cy5 and DAPI channels) were acquired using a fluorescence microscope to visualize the distribution of active cathepsins within the tumor and normal tissue architecture. [2] |
| Animal Protocol |
Animal/Disease Models: balb/c (Bagg ALBino) mouse bearing 4T1 cells[1]
Doses: 20 nmol Route of Administration: Tail vein Experimental Results: Robust tumor specific activation of fluorescence with high overall intensity could be observed. For labeling active cathepsins in cultured cells, cancer cell lines (e.g., MDA-MB-231) were lysed. Cell lysates were incubated with the probe L-217 (BMV109-Cy5 conjugate) at a specific concentration for a defined period (e.g., 1 hour at 37°C). To confirm labeling specificity, lysates were pre-incubated with a broad-spectrum cathepsin inhibitor (JPM-OEt) for 30 minutes prior to adding L-217. After incubation, the reaction was stopped, and proteins were separated by SDS-PAGE under non-reducing conditions. The labeled cathepsins were visualized directly in the gel using a fluorescence scanner specific for the Cy5 fluorophore. Band intensity indicated the amount of active enzyme present. [1] For ex vivo tissue imaging, fresh frozen human colon cancer tissue sections were cut. Tissue sections were incubated with the probe L-217 (BMV109-Cy5 conjugate) in buffer for a set time (e.g., 1 hour at 37°C). Sections were then washed, fixed, counterstained with DAPI for nuclei, and mounted. Fluorescence images (Cy5 and DAPI channels) were acquired using a fluorescence microscope to visualize the distribution of active cathepsins within the tumor and normal tissue architecture. [2] |
| ADME/Pharmacokinetics |
Specific ADME/PK data (e.g., Cmax, Tmax, AUC, t1/2, CL, Vd, F%) for BMV109 itself were not reported in [1] and [2]. These studies focused primarily on the distribution and activation kinetics of the BMV109-derived probe L-217. [1][2] For probe L-217 (BMV109-Cy5 conjugate) in mice: Imaging in xenograft mice showed that the probe circulated in vivo and accumulated specifically in tumors over time, and was activated (lysed) within the tumor. The tumor-to-background concentration ratio peaked 24 hours after intravenous injection. The signal persisted but decreased after 48 hours. Ex vivo imaging confirmed that the probe concentration/activation level in tumors was higher than in other organs at 24 hours. [1]
Regarding the application of probe L-217 (BMV109-Cy5 conjugate) in humans: Fluorescence endoscopy performed 1-3 days after intravenous injection successfully detected tumor-specific signals in colorectal cancer patients, indicating that the probe reached and activated the target lesion within this time range. [2] |
| Toxicity/Toxicokinetics |
Regarding the use of probe L-217 (BMV109-Cy5 conjugate) in humans: The first human clinical trial ([2]) reported that intravenous administration of 0.13 mg/kg of L-217 was well tolerated. No adverse events related to the probe were observed in the 15 enrolled patients. Vital signs remained stable before and after probe administration. This indicates that the probe has good safety at the administered dose in this specific situation. [2]
|
| References |
|
| Additional Infomation |
BMV109 is described as a potent, irreversible inhibitor of pan-cathepsins. It contains an electrophilic epoxy succinyl reactive head that covalently modifies the cysteine residues at the active sites of cathepsins B, L, S, and V. [1] In [1], BMV109 is used as a key quenching component in the design of the quenching fluorescent probe ABP L-217. The probe is formed by linking BMV109 to the fluorophore Cy5 via a self-cleaving p-aminobenzyloxycarbonyl (PABC) spacer. This design allows the fluorophore to remain quenched until the probe is activated by specific proteolytic enzymes within the active site of the target enzyme. [1] The primary purpose of using BMV109 in [1] and [2] is to use it as a targeting ligand and irreversible inhibitor of cathepsins in fluorescent active probes (ABPs, especially L-217). Its function is to ensure that the fluorophore is specifically delivered to the active cathepsin and to retain the signal through covalent binding. [1][2]
[2] The study first applied the active proteomics probe (L-217, derived from BMV109) to human clinical practice for real-time wide-field fluorescence endoscopy imaging to detect the activity of cancer-associated proteases (cathepsins). This study successfully demonstrated that it can distinguish between colorectal cancer and normal mucosa in patients. [2] |
| Molecular Formula |
C107H108N10O23F4S5
|
|---|---|
| Molecular Weight |
2138.37
|
| Exact Mass |
2136.6128
|
| Elemental Analysis |
C, 60.10; H, 5.09; F, 3.55; N, 6.55; O, 17.21; S, 7.50
|
| CAS # |
1458731-58-2
|
| Appearance |
Typically exists as solid at room temperature
|
| SMILES |
S(N1CCC(C(=O)NCCNC(C2C(=C(F)C(OCC(=O)[C@H](CCCCNC(=O)CCCCCN3C(C(C)(C)C4=CC(S(O)(=O)=O)=CC=C34)=CC=CC=CC3C(C4=CC(S([O-])(=O)=O)=CC=C4[N+]=3CC)(C)C)NC(=O)[C@@H](NC(=O)OCC3C=CC=CC=3)CC3C=CC=CC=3)=C(F)C=2F)F)=O)CC1)(C1C=CC=CC=1C1=C2C=CC(N3CCC4=CC(S(O)(=O)=O)=CC=C34)=CC2=[O+]C2C=C(N3CCC4=CC(S([O-])(=O)=O)=CC=C34)C=CC1=2)(=O)=O
|
| InChi Key |
KDFGXWUMTFTKSD-XYZCXLSZSA-N
|
| InChi Code |
InChI=1S/C107H108F4N10O23S5/c1-6-118-86-43-37-75(148(136,137)138)62-80(86)106(2,3)92(118)30-15-9-16-31-93-107(4,5)81-63-76(149(139,140)141)38-44-87(81)121(93)52-22-10-17-32-94(123)112-49-21-20-28-82(115-103(125)83(57-66-23-11-7-12-24-66)116-105(127)143-64-67-25-13-8-14-26-67)88(122)65-142-101-99(110)97(108)96(98(109)100(101)111)104(126)114-51-50-113-102(124)68-45-53-117(54-46-68)145(128,129)91-29-19-18-27-79(91)95-77-39-33-71(119-55-47-69-58-73(146(130,131)132)35-41-84(69)119)60-89(77)144-90-61-72(34-40-78(90)95)120-56-48-70-59-74(147(133,134)135)36-42-85(70)120/h7-9,11-16,18-19,23-27,29-31,33-44,58-63,68,82-83H,6,10,17,20-22,28,32,45-57,64-65H2,1-5H3,(H7-2,112,113,114,115,116,123,124,125,126,127,130,131,132,133,134,135,136,137,138,139,140,141)/t82-,83-/m0/s1
|
| Chemical Name |
1-((E)-9-(2-((4-((2-(4-(((S)-7-(6-((E)-2-((2E,4E)-5-(5-((l1-oxidaneyl)dioxo-l6-sulfaneyl)-1-ethyl-3,3-dimethyl-3H-indol-1-ium-2-yl)penta-2,4-dien-1-ylidene)-3,3-dimethyl-5-sulfoindolin-1-yl)hexanamido)-3-((S)-2-(((benzyloxy)carbonyl)amino)-3-phenylpropanamido)-2-oxoheptyl)oxy)-2,3,5,6-tetrafluorobenzamido)ethyl)carbamoyl)piperidin-1-yl)sulfonyl)phenyl)-6-(5-sulfoindolin-1-yl)-3H-xanthen-3-ylidene)-1l4-indoline-5-sulfonate
|
| Synonyms |
BMV109; BMV-109; BMV 109;
|
| 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 | 0.4676 mL | 2.3382 mL | 4.6765 mL | |
| 5 mM | 0.0935 mL | 0.4676 mL | 0.9353 mL | |
| 10 mM | 0.0468 mL | 0.2338 mL | 0.4676 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
