Physicochemical Properties
| Molecular Formula | C9H13CLN6O2 |
| Molecular Weight | 272.69 |
| Exact Mass | 272.079 |
| CAS # | 42471-28-3 |
| Related CAS # | Nimustine hydrochloride;55661-38-6 |
| PubChem CID | 39214 |
| Appearance | Typically exists as solid at room temperature |
| Density | 1.52g/cm3 |
| LogP | 1.771 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 18 |
| Complexity | 292 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CC1=NC=C(C(N1)=N)CNC(N(N=O)CCCl)=O |
| InChi Key | VFEDRRNHLBGPNN-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C9H13ClN6O2/c1-6-12-4-7(8(11)14-6)5-13-9(17)16(15-18)3-2-10/h4H,2-3,5H2,1H3,(H,13,17)(H2,11,12,14) |
| Chemical Name | 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-1-(2-chloroethyl)-1-nitrosourea |
| 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 | Nimustine (50 μM; 72-120 h) induces apoptosis in cells, which results in cell death[1]. The DNA damage response system is activated by nimomycin (50 μM; 24-96 h)[1]. In glioma cells, nimustine (50 μM; 24-120 h) stimulates MAPK signaling[1]. |
| ln Vivo | Nimustine efficiently slows tumor growth, with the higher dose being more effective[2]. Nimustine should be taken 15 times per week or 30 mg/kg twice with a two-week interval. |
| Cell Assay |
Apoptosis Analysis[1] Cell Types: LN-229 cell line Tested Concentrations: 50 μM Incubation Duration: 72-120 hrs (hours) Experimental Results: Time-dependently induced apoptosis. Western Blot Analysis[1] Cell Types: LN-229 and glioma cell lines Tested Concentrations: 50 μM Incubation Duration: 24-120 hrs (hours) Experimental Results: Induced cleavage of caspase-8 and -9 and the effector caspase-3. Increased phosphorylation of ERK kinase and H2AX. |
| Animal Protocol |
Animal/Disease Models: Female C3H/HeN mice with solid FM3A tumors[2] Doses: 15 and 30 mg/kg Route of Administration: intravenous (iv)injection; 15 (4 times a week) and 30 mg/kg (twice with an interval of 2 weeks) Experimental Results: The intermittent large-dose injections resulted in better inhibition of tumor growth than did the fractionated small-dose injections. |
| References |
[1]. Apoptosis induced by temozolomide and nimustine in glioblastoma cells is supported by JNK/c-Jun-mediated induction of the BH3-only protein BIM. Oncotarget. 2015 Oct 20;6(32):33755-68. [2]. Effects of combined treatment with nimustine hydrochloride and radiation on solid FM3A tumor in mice. Jpn J Cancer Res. 1987 Jul;78(7):756-62. |
| Additional Infomation |
Nimustine is an organochlorine compound that is urea in which the two hydrogens on one of the amino groups are replaced by nitroso and 2-chloroethyl groups and one hydrogen from the other amino group is replaced by a 4-amino-2-methylpyrimidin-5-ylmethyl] group. An antineoplastic agent especially effective against malignant brain tumors. It has a role as an alkylating agent and an antineoplastic agent. It is an organochlorine compound, an aminopyrimidine and a member of N-nitrosoureas. It is a conjugate base of a nimustine(1+). Nimustine has been used in trials studying the treatment of Glioblastoma. Nimustine is a nitrosourea with antineoplastic activity. Nimustine alkylates and crosslinks DNA, thereby causing DNA fragmentation, inhibition of protein synthesis, and cell death. (NCI05) Antineoplastic agent especially effective against malignant brain tumors. The resistance which brain tumor cells acquire to the initial effectiveness of this drug can be partially overcome by the simultaneous use of membrane-modifying agents such as reserpine, calcium antagonists such as nicardipine or verapamil, or the calmodulin inhibitor, trifluoperazine. The drug has also been used in combination with other antineoplastic agents or with radiotherapy for the treatment of various neoplasms. |
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 | 3.6672 mL | 18.3358 mL | 36.6717 mL | |
| 5 mM | 0.7334 mL | 3.6672 mL | 7.3343 mL | |
| 10 mM | 0.3667 mL | 1.8336 mL | 3.6672 mL |