2. Membrane Transporter/Ion Channel
  3. Urea Transporter
  4. PU-48

PU-48 is a blood-brain barrier-permeable urea transporter (UT) inhibitor with an IC50 of 0.32 μM against rat UT-A. By functionally inhibiting urea transporters (including UT-A subtypes) in the renal inner medullary collecting ducts, PU-48 induces urea-selective diuresis. PU-48 does not alter blood levels of sodium, potassium or chloride ions, nor does it affect the excretion of non-urea solutes. PU-48 shows no significant toxicity in cell or animal models and can be used in edema-related research.

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PU-48

PU-48 Chemical Structure

CAS No. : 335394-78-0

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PU-48 Related Antibodies

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Description

PU-48 is a blood-brain barrier-permeable urea transporter (UT) inhibitor with an IC50 of 0.32 μM against rat UT-A. By functionally inhibiting urea transporters (including UT-A subtypes) in the renal inner medullary collecting ducts, PU-48 induces urea-selective diuresis. PU-48 does not alter blood levels of sodium, potassium or chloride ions, nor does it affect the excretion of non-urea solutes. PU-48 shows no significant toxicity in cell or animal models and can be used in edema-related research[1][2][3].

In Vitro

PU-48 (0.25-4 µg/mL; 24 h) exhibits high plasma protein binding (over 89%) in human plasma, with no concentration-dependent differences across the tested concentrations[2].
PU-48 (10-9-10-4 M; 6 min) potently and specifically inhibits UT-B-mediated urea transport in human, rat, and mouse erythrocytes with IC50 values of 0.21 μM, 0.33 μM, and 2.1 μM, respectively[3].
PU-48 (4 μM; 60 min) inhibits UT-A1-mediated urea transport in UT-A1-expressing Type I MDCK cells with an IC50 of 0.32 μM, which is ~2.8-fold more potent than its inhibition of UT-B-mediated transport in UT-B-expressing Type I MDCK cells (IC50=0.90 μM)[3].
PU-48 (5-80 μM; 72 h) does not exhibit cytotoxicity in Type I MDCK cells at concentrations up to 80 μM after 72 h incubation[3].
PU-48 (10 μM) does not inhibit hERG, NaV1.5, or CaV1.2 channel activity in stably transfected HEK293 cells[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

PU-48 Related Antibodies

Cell Cytotoxicity Assay[3]

Cell Line: Type I MDCK cells
Concentration: 5-80 μM
Incubation Time: 72 h
Result: Did not significantly reduce MDCK cell viability at concentrations up to 80 μM, with viability remaining near 100% relative to controls.
Parmacokinetics
Species Dose Route Cmax Tmax AUC0-t AUC0-∞ T1/2
Rat[2] 3 mg/kg p.o. 12.6 ng/mL 1.19 h 60.0 ng·h/mL 60.5 ng·h/mL 7.14 h
Rat[2] 6 mg/kg p.o. 52.9 ng/mL 0.63 h 106.8 ng·h/mL 108.2 ng·h/mL 7.00 h
Rat[2] 12 mg/kg p.o. 94.3 ng/mL 0.50 h 178.9 ng·h/mL 180.7 ng·h/mL 6.87 h
In Vivo

PU-48 (12 mg/kg; p.o.; single dose) rapidly and extensively distributes across tissues in healthy rats, with high concentrations in the gastrointestinal tract, liver, kidney, and bladder (target tissues for diuretic activity), crosses the blood-brain barrier, and shows no tissue accumulation over 24 hours[2].
PU-48 (100 mg/kg; s.c.; single dose) induces urea-selective diuresis in both UT-B null and wild-type male C57BL/6 mice without altering electrolyte excretion[3].
PU-48 (3.125-50 mg/kg; s.c.; single dose) induces dose-dependent diuresis in male SD rats at subcutaneous doses of 12.5 and 50 mg/kg, with peak efficacy at 2 h post-administration[3].
PU-48 (50-100 mg/kg; s.c.; every 8 h; 6 days) induces sustained diuresis in male SD rats with twice-daily subcutaneous dosing of 50 mg/kg (first dose 100 mg/kg) for 6 days, without causing electrolyte imbalance or altering renal transporter/aquaporin protein expression[3].
PU-48 (14 g/kg; p.o.; single dose) shows no acute toxicity in 4-week-old male and female CD-ICR mice[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: C57BL/6 UT-B null mice (10-week-old male, ~25 g); C57BL/6 wild-type mice (10-week-old male, ~25 g)[3]
Dosage: 100 mg/kg
Administration: s.c.; single dose
Result: Significantly increased urine output in both UT-B null and wild-type mice.
Decreased urinary osmolality in both UT-B null and wild-type mice.
Decreased urinary urea concentration in both UT-B null and wild-type mice.
Decreased urinary non-urea solute concentration in both UT-B null and wild-type mice.
Increased urea excretion in both UT-B null and wild-type mice.
Did not change excretion of non-urea solutes (including Na+, K+, Cl-) in either group.
Reached peak changes at 2 h post-administration, with values returning to basal levels by 10 h.
Animal Model: Sprague-Dawley (SD) rats (male, 200~220 g)[3]
Dosage: 3.125 mg/kg; 12.5 mg/kg; 50 mg/kg
Administration: s.c.; single dose
Result: Caused a dose-dependent increase in urine output at doses of 12.5 and 50 mg/kg.
Significantly reduced urinary osmolality at doses of 12.5 and 50 mg/kg (P<0.05).
Significantly reduced urinary urea concentration at doses of 12.5 and 50 mg/kg (P<0.05).
Showed no significant effect at the 3.125 mg/kg dose.
Reached peak changes at 2 h post-administration, with values returning to basal levels by 10 h.
Animal Model: Sprague-Dawley (SD) rats (male, 200~220 g)[3]
Dosage: 50 mg/kg; 100 mg/kg (first dose)
Administration: s.c.; every 8 h; 6 days
Result: Caused continuous diuresis over the 6-day treatment period, with diuretic efficacy similar to that of hydrochlorothiazide (HCTZ).
Reduced urinary osmolality over the 6-day treatment period.
Reduced urinary urea concentration over the 6-day treatment period.
Did not significantly alter blood levels of Na+, K+, Cl-, urea, glucose, cholesterol, or triglycerides compared to vehicle controls.
Significantly reduced inner medullary tissue osmolality.
Significantly reduced inner medullary urea concentration.
Did not affect inner medullary Na+ or Cl- concentrations.
Caused no significant changes in renal protein expression levels of UT-A1, UT-A2, UT-A3, UT-B, AQP1, AQP2, AQP3, AQP4, NCC, or NKCC2.
Molecular Weight

288.32

Formula

C14H12N2O3S
CAS No.
Appearance

Solid

Color

Light yellow to yellow

SMILES

O=C(C1=C(N)C2=C(N=C3C=CC(OC)=CC3=C2)S1)OC
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

4°C, protect from light, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

Solvent & Solubility
In Vitro: 

DMSO : 6.67 mg/mL (23.13 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 3.4684 mL 17.3418 mL 34.6837 mL
5 mM 0.6937 mL 3.4684 mL 6.9367 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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Purity & Documentation
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 3.4684 mL 17.3418 mL 34.6837 mL 86.7092 mL
5 mM 0.6937 mL 3.4684 mL 6.9367 mL 17.3418 mL
10 mM 0.3468 mL 1.7342 mL 3.4684 mL 8.6709 mL
15 mM 0.2312 mL 1.1561 mL 2.3122 mL 5.7806 mL
20 mM 0.1734 mL 0.8671 mL 1.7342 mL 4.3355 mL
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PU-48 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

PU-48335394-78-0PU48PU 48Urea TransporterhERGUT-AUT-BType I MDCK cellsurea transporterCaV1.2HEK293 cellsinner medullary collecting ducterythrocytesNaV1.5Inhibitorinhibitorinhibit

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