Aminobutane bisphosphonate (compound 8) inhibited the activity of purified farnesyl pyrophosphate synthase from Trypanosoma cruzi, with an IC50 value of 30.77 μM[1]. At concentrations up to 100 μM, aminobutane bisphosphonate did not inhibit the proliferation of epiflagellates in Trypanosoma cruzi, therefore IC50 > 100 μM[1]. At a concentration of 85 μM, aminobutane bisphosphonate inhibited only 13% of the proliferation of aflagellates in Trypanosoma cruzi, therefore IC50 > 85 μM[1].

Aminobutane bisphosphonates (compound 8) (0.01–1.0 mg P per kg; subcutaneous injection; for 2 consecutive days prior to surgery) inhibited fixation-induced bone loss in male Sprague-Dawley rats in a dose-dependent manner. A dose of 0.10 mg P per kg eliminated the difference in trabecular volume between intact and fixed limbs at 20 days and reduced the percentage difference in femoral ash weight/length to 7.0% [2].

Animal/Disease Models:Sprague-Dawley mice (male, 250-280 g, bone loss induced by unilateral sciatic nerve resection and fixation) [2]
Doses: 0.01 mg/kg; 0.10 mg/kg; 1.0 mg/kg
Route of Administration: Subcutaneous injection; 2 consecutive days before surgery
Experimental Results: Compared with the solvent control group, the femoral ash weight of both intact and fixed limbs increased in a dose-dependent manner at 10 and 20 days postoperatively (p < 0.05). The 0.10 mg/kg dose eliminated the decrease in femoral ash weight induced by fixation at 10 days postoperatively. At 20 days, the 0.10 mg P/kg dose group and the 1.0 mg P/kg dose group reduced the percentage difference in femoral ash weight/length between intact and fixed limbs from 11.5% in the carrier control group to 7.0% and 4.8%, respectively. At day 20, femoral length decreased from 36.6 mm (intact limb) and 36.4 mm (fixed limb) to 35.6 mm in the 1.0 mg P/kg dose group (p < 0.05). At day 10, trabecular volume increased to 52.1% (intact limb) and 41.0% (fixed limb) in the 0.10 mg P/kg dose group, compared to 17.9% (intact limb) and 7.9% (fixed limb) in the carrier control group (p < 0.05). At day 20, trabecular volume increased in a dose-dependent manner: 22.9% in the 0.01 mg P/kg dose group (intact limb) and 15.5% in the fixed limb; 37.6% in the 0.10 mg P/kg dose group (intact limb) and 35.4% in the fixed limb; and 71.6% in the 1.0 mg P/kg dose group (intact limb) and 68.1% in the fixed limb (p < 0.05 compared to the control group for all dose groups). Both the 0.10 mg P/kg and 1.0 mg P/kg dose groups eliminated the difference in trabecular volume between intact and fixed limbs at day 20. Compared with the control group, all dose groups reduced the number of osteoclasts per millimeter of trabecular surface in both limbs at day 20 (p < 0.05), thereby eliminating the difference between intact and fixed limbs observed in the control group. At day 20, bone erosion area was significantly reduced in both the 0.01 mg P/kg group (12.1% of intact limbs, 12.3% of fixed limbs) and the 1.0 mg P/kg group (16.1% of intact limbs, 15.8% of fixed limbs); the bone erosion area of the fixed limb in the 0.10 mg P/kg group was also significantly reduced (17.7%), which was significantly different from the carrier control group (p < 0.05). On day 10, the osteoid tissue area decreased to 0.4% (intact limb) and 0.1% (fixed limb) in the 0.10 mg P/kg group, compared to 6.0% (intact limb) and 2.4% (fixed limb) in the carrier control group (p < 0.05). On day 20, the osteoid tissue area decreased in a dose-dependent manner: 1.3% (intact limb) in the 0.01 mg P/kg group; after administration of 0.10 mg/kg phosphorus, bone deposition rate decreased by 0.2% in intact limbs and 0.3% in fixed limbs; after administration of 1.0 mg/kg phosphorus, bone deposition rate decreased by 0.2% in intact limbs and 0.1% in fixed limbs (all p < 0.05, compared with the carrier control group). Compared with the carrier control group (0.97 μm/day), administration of 0.10 mg/kg and 1.0 mg/kg phosphorus reduced bone deposition rate in intact limbs by 14% (0.82 μm/day and 0.83 μm/day, respectively; p<0.05), but did not further reduce bone deposition rate in immobilized limbs.

[1]. Synthesis and biological evaluation of 1-amino-1,1-bisphosphonates derived from fatty acids against Trypanosoma cruzi targeting farnesyl pyrophosphate synthase. Bioorg Med Chem Lett. 2005;15(21):4685-4690.

[2]. Aminohydroxybutane bisphosphonate inhibits bone loss due to immobilization in rats. J Bone Miner Res. 1990;5(3):279-286.

C4H13NO6P2

233.10

32545-60-1

Typically exists as solids at room temperature

O=P(O)(C(CCC)(P(O)(O)=O)N)O

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

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.

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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).

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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)

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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).

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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

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)