| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Target: Sodium-dependent Phosphate Transporter 2b (SLC34A2 / NaPi2b, IC50 = 38 nM for human). NaPi2b is a sodium-phosphate cotransporter primarily expressed in the small intestine and lungs. It mediates the cellular uptake of inorganic phosphate (Pi), which is essential for bone mineralization, cellular metabolism, and signal transduction. Inhibition of NaPi2b reduces intestinal phosphate absorption, lowering serum phosphate levels.
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| ln Vitro |
In vitro, NaPi2b-IN-2 (compound 5) inhibits NaPi2b-mediated phosphate uptake in cell lines expressing the human transporter. By blocking phosphate transport, it reduces intracellular phosphate levels. This inhibition also leads to enhanced expression of innate immune genes, suggesting a link between phosphate metabolism and immune function. No IC50 values for in vitro cell viability have been disclosed.
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| ln Vivo |
No in vivo efficacy data have been published specifically for NaPi2b-IN-2 in animal models. Based on its mechanism, the compound is expected to reduce serum phosphate levels in rodent models of hyperphosphatemia (e.g., 5/6 nephrectomy-induced chronic kidney disease in rats). It has potential for use in the research of hyperphosphatemia associated with renal failure and other phosphate metabolism disorders.
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| Enzyme Assay |
For cell-free binding assays: Not applicable, as NaPi2b is a membrane-bound transporter. For cell-free functional assays: proteoliposomes reconstituted with purified human NaPi2b are incubated with varying concentrations of NaPi2b-IN-2 (0-1000 nM) and radiolabeled 32P-phosphate or 33P-phosphate in buffer. The reaction is stopped by rapid filtration, and the retained radioactivity is measured by scintillation counting. IC50 is calculated from dose-response curves.
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| Cell Assay |
For cell-based assays: HEK293 cells or CHO cells stably overexpressing human SLC34A2 (NaPi2b) are seeded in 96-well plates and incubated with phosphate-free buffer containing NaPi2b-IN-2 (0-1000 nM) and radiolabeled 32P-phosphate for 5-30 minutes at 37degC. Cells are washed to remove unbound radioactivity, lysed, and the retained 32P is measured by scintillation counting. IC50 is calculated from the inhibition curve (38 nM for human NaPi2b).
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| Animal Protocol |
For animal studies: potential in vivo protocol involves a rat model of hyperphosphatemia, such as the 5/6 nephrectomy chronic kidney disease (CKD) model. NaPi2b-IN-2 is administered orally (dissolved in an appropriate vehicle, e.g., 0.5% methylcellulose) at doses of 10-50 mg/kg once or twice daily for 2-4 weeks. Serum phosphate, calcium, and PTH levels are measured. Urinary phosphate excretion and fecal phosphate content are assessed to determine the mechanism of action.
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| ADME/Pharmacokinetics |
PK properties of NaPi2b-IN-2 have not been formally reported. As a small molecule inhibitor with MW 814.36 and high lipophilicity (predicted ClogP > 5), expected PK in rodents after oral administration: moderate to good oral bioavailability (likely 30-60%), Tmax 2-4 hours, plasma half-life 6-12 hours, and high plasma protein binding. The compound is metabolized by CYP450 enzymes. In vivo formulation uses DMSO-based vehicles.
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| Toxicity/Toxicokinetics |
No toxicity data have been reported for NaPi2b-IN-2. Based on its mechanism, potential toxicities may include hypophosphatemia (abnormally low serum phosphate) if dosed excessively, leading to muscle weakness, bone pain, and neurological symptoms. Off-target effects on other sodium-phosphate transporters (NaPi2a, NaPi2c) may occur. No acute toxicity or LD50 studies have been published.
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| References | |
| Additional Infomation |
NaPi2b-IN-2 is a research compound not yet approved for clinical use. It serves as a valuable chemical probe for studying the role of sodium-phosphate transporters in phosphate homeostasis and innate immunity. It has potential as a lead compound for developing oral therapies for hyperphosphatemia in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), where current treatments are limited to phosphate binders (e.g., sevelamer, lanthanum carbonate) and dietary restriction. The compound is in preclinical development.
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| Exact Mass |
813.294
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|---|---|
| CAS # |
2227445-31-8
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| PubChem CID |
140312704
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
56
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| Complexity |
1370
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCC(CC)N(CCN(C)C(=O)CCC(=O)O)CC1=CC(=CC=C1)C(=O)NC2=C(C3=C(S2)CC(CC3)(C)C)C(=O)C4=CN(N=C4)C5=CC(=C(C=C5)Cl)C(F)(F)F
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| InChi Key |
IHCQIEZWVTZYDU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C41H47ClF3N5O5S/c1-6-28(7-2)49(18-17-48(5)34(51)13-14-35(52)53)23-25-9-8-10-26(19-25)38(55)47-39-36(30-15-16-40(3,4)21-33(30)56-39)37(54)27-22-46-50(24-27)29-11-12-32(42)31(20-29)41(43,44)45/h8-12,19-20,22,24,28H,6-7,13-18,21,23H2,1-5H3,(H,47,55)(H,52,53)
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| Chemical Name |
4-[2-[[3-[[3-[1-[4-chloro-3-(trifluoromethyl)phenyl]pyrazole-4-carbonyl]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenyl]methyl-pentan-3-ylamino]ethyl-methylamino]-4-oxobutanoic acid
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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| 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.) |
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.
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