Fostroxacitabine bralpamide (MIV-818) is an orally bioactive Troxacitabine-based nucleotide precursor with anti-cancer activities.

Physicochemical Properties

Molecular Formula	C22H30BRN4O8P
Molecular Weight	589.37
Exact Mass	588.098
CAS #	2129993-56-0
Related CAS #	2416950-25-7 (HCl);2129993-56-0;
PubChem CID	141649565
Appearance	Typically exists as solid at room temperature
LogP	2.2
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	13
Heavy Atom Count	36
Complexity	882
Defined Atom Stereocenter Count	5
SMILES	CCC[C@H](C)OC(=O)[C@H](C)N[P@](=O)(OC[C@H]1OC[C@H](O1)N2C=CC(=NC2=O)N)OC3=CC=C(C=C3)Br
InChi Key	JBYKMODFCUCTGY-LLSQRQBFSA-N
InChi Code	InChI=1S/C22H30BrN4O8P/c1-4-5-14(2)33-21(28)15(3)26-36(30,35-17-8-6-16(23)7-9-17)32-13-20-31-12-19(34-20)27-11-10-18(24)25-22(27)29/h6-11,14-15,19-20H,4-5,12-13H2,1-3H3,(H,26,30)(H2,24,25,29)/t14-,15-,19-,20-,36-/m0/s1
Chemical Name	[(2S)-pentan-2-yl] (2S)-2-[[[(2S,4S)-4-(4-amino-2-oxopyrimidin-1-yl)-1,3-dioxolan-2-yl]methoxy-(4-bromophenoxy)phosphoryl]amino]propanoate
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	Fostroxacitabine bralpamide (MIV-818) is extensively digested by human hepatocytes, which causes the liver to receive high concentrations of the chain-terminating nucleotide triphosphate. During DNA replication, triphosphate is incorporated into the molecule, resulting in DNA double strand breaks, damage responses to the DNA, and cytotoxicity[1].
References	[1]. Phase I study of the novel pro-drug MIV-818 in patients with hepatocellular carcinoma, intra-hepatic cholangiocarcinoma or liver metastases.
Additional Infomation	Fostroxacitabine Bralpamide is a liver-targeting nucleotide phosphoramidate prodrug of troxacitabine monophosphate (TRX-MP), a dioxolane derivative and L-configuration deoxycytidine analogue, with potential antineoplastic activity. Upon oral administration, fostroxacitabine bralpamide is rapidly and specifically hydrolyzed in hepatocytes by liver carboxylesterase 1 (carboxylesterase 1, CE-1), generating high levels of the chain-terminating nucleotide, troxacitabine triphosphate (TRX-TP) in the liver. TRX-TP is then incorporated into tumor cell DNA, leading to termination of DNA synthesis and inhibition of tumor cell proliferation.

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	1.6967 mL	8.4836 mL	16.9673 mL
	5 mM	0.3393 mL	1.6967 mL	3.3935 mL
	10 mM	0.1697 mL	0.8484 mL	1.6967 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.