Physicochemical Properties
| Molecular Formula | C11H20N3O14P3 |
| Molecular Weight | 511.2093 |
| Exact Mass | 511.016 |
| CAS # | 332863-86-2 |
| Related CAS # | MBC-11 trisodium;387877-45-4;MBC-11 triethylamine |
| PubChem CID | 44463769 |
| Appearance | Typically exists as solid at room temperature |
| LogP | -6.1 |
| Hydrogen Bond Donor Count | 8 |
| Hydrogen Bond Acceptor Count | 14 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 31 |
| Complexity | 934 |
| Defined Atom Stereocenter Count | 4 |
| SMILES | P(C(C)(O)P(=O)(O)O)(=O)(O)OP(=O)(O)OC[C@@H]1[C@H]([C@@H]([C@H](N2C(N=C(C=C2)N)=O)O1)O)O |
| InChi Key | HUIKCRXUQCSUJS-ZLRZYOKSSA-N |
| InChi Code | InChI=1S/C11H20N3O14P3/c1-11(18,29(19,20)21)30(22,23)28-31(24,25)26-4-5-7(15)8(16)9(27-5)14-3-2-6(12)13-10(14)17/h2-3,5,7-9,15-16,18H,4H2,1H3,(H,22,23)(H,24,25)(H2,12,13,17)(H2,19,20,21)/t5-,7-,8+,9-,11?/m1/s1 |
| Chemical Name | [1-[[[(2R,3S,4S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]-1-hydroxyethyl]phosphonic acid |
| Synonyms | MBC11; MBC 11; MBC-11 |
| 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) |
Biological Activity
| ln Vitro | MBC-11 strongly suppressed the proliferation of all three cell lines between 10-8 and 10-4 M, exhibiting similar activity patterns. KAS-6/1 cell growth was decreased by MBC-11 from roughly 56% at 10-8 M to 6% at 10-8 M. 10-5M [1]. |
| ln Vivo | In patients treated with PBS (90%) or 0.04 μg/day zoledronate (100%), the incidence of bone metastases was reduced by 40% by MBC-11 (0.04 μg/day, subcutaneous). In comparison to mice given PBS or zoledronate, MBC-11 also dramatically decreased the burden of bone tumors [1]. Mice given 500 μg/day of MBC-11 experienced weight increase comparable to the PBS-treated group [1]. These findings suggest that MBC-11 merits more research as a treatment for tumor-induced bone disease (TIBD) since it can lessen the burden of bone tumors, preserve bone structure, and possibly increase overall survival [1]. |
| Cell Assay |
Cell proliferation assay [1] Cell Types: human multiple myeloma cell lines (KAS-6/1, DP-6, KP-6). Tested Concentrations: between 10-8 and 10-4 M. Incubation Duration: 48 hrs (hours). Experimental Results: Significant inhibition of multiple myeloma cell proliferation across cell lines at most concentrations tested. |
| Animal Protocol |
Animal/Disease Models: Approximately 4weeks old female balb/c (Bagg ALBino) mouse are inoculated (subcutaneously (sc) (sc) into their mammary fat pad) with 500,000 4T1/luc cells (a mammary tumor model) on day 0 [1]. Doses: 0.04, 0.4 or 4.0 mcg/day. Route of Administration: Daily subcutaneous injection from days 7 to 21. Experimental Results: The 0.04 μg/day dose resulted in a lower incidence of bone metastases compared with PBS or 0.04 μg/day zoledronic acid treatment. Animal/Disease Models: Female Balb/c and SCID (severe combined immunodeficient) mouse (4-6 weeks old) [1]. Doses: 500, 100, 1 or 0.01 μg/100 μL. Route of Administration: Daily subcutaneous injection for 24 or 49 days. Experimental Results: The weight gain of mice in different doses of MBC-11 treatment groups was similar to that of the PBS treatment group. |
| References |
[1]. Reinholz MM, et al. A promising approach for treatment of tumor-induced bone diseases: utilizing bisphosphonate derivatives of nucleoside antimetabolites. Bone. 2010 Jul;47(1):12-22. [2]. Zinnen SP, et al. First-in-Human Phase I Study of MBC-11, a Novel Bone-Targeted Cytarabine-Etidronate Conjugate in Patients with Cancer-Induced Bone Disease. Oncologist. 2019 Mar;24(3):303-e102. |
| Additional Infomation | Etidronate-Cytarabine Conjugate MBC-11 is a synthetic conjugate composed of the bisphosphonate etidronate linked to the cytostatic agent and antimetabolite cytarabine, with potential antineoplastic and antiresorptive activities. Upon intravenous administration of the etidronate-cytarabine conjugate MBC-11, the etidronate moiety targets bone and the two moieties are released upon hydrolysis. Etidronate binds to hydroxyapatite crystals in bone tissues and prevents its resorption. This prevents bone destruction and induces bone cell mineralization. In addition, the bone-targeting nature of this agent allows for the accumulation of cytarabine in bone tissue, where it is able to exert its antitumor effect locally by competing with cytidine for incorporation into DNA, thereby inhibiting DNA synthesis, while reducing systemic exposure. This leads to a destruction of bone-associated tumor cells, an inhibition of tumor cell proliferation and bone metastasis, and prevents tumor-mediated bone destruction. |
Solubility Data
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9561 mL | 9.7807 mL | 19.5614 mL | |
| 5 mM | 0.3912 mL | 1.9561 mL | 3.9123 mL | |
| 10 mM | 0.1956 mL | 0.9781 mL | 1.9561 mL |