| Size | Price | |
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| 100g | ||
| Other Sizes |
Purity: ≥98%
Picolinamide (2-Pyridinecarboxamide, Picolinoylamide, 2-Carbamoylpyridine) is found to be a strong inhibitor of poly (ADP-ribose) synthetase of nuclei from rat pancreatic islet cells. In a prior investigation, picolinamide was employed to assess the potential correlation between the inhibition of NAD hydrolyzing enzymes and the inhibition of Na+/phosphate cotransport. The inhibition of Na+/phosphate cotransport by isolated renal brush border membrane vesicles was demonstrated by the results of an overnight picolinamide treatment of rats.
| Targets |
PARP ( IC50 = 95 μM )
Poly(ADP-ribose) synthetase (PARP) [2] - Renal Na+/phosphate cotransporter [1] |
|---|---|
| ln Vitro |
In vitro activity: Picolinamide (10 μM-1 mM) suppresses the activity of Poly(ADP-ribose) synthetase[2]. In rat renal cortical brush-border membrane vesicles, Picolinamide exhibited concentration-dependent inhibition of Na+-dependent phosphate transport. At 1 mM, it inhibited phosphate uptake by approximately 70%, with no significant effect on Na+-independent phosphate transport or Na+/glucose cotransport [1] - In isolated rat pancreatic islets treated with streptozotocin (STZ, 5 mM) or alloxan (10 mM), Picolinamide (1 mM) protected against DNA strand breaks, as detected by alkaline elution assay. It reversed the STZ/alloxan-induced reduction in proinsulin synthesis (restored to 85% of control levels) and prevented NAD+ depletion (NAD content maintained at 78% of control) [2] - In rat pancreatic islets, Picolinamide (1 mM) blocked poly(ADP-ribose) synthetase activation induced by STZ, inhibiting the consumption of NAD+ and ATP. This preservation of energy metabolism restored proinsulin synthesis, which was reduced by STZ treatment (from 2.1 pmol/islet/h to 0.8 pmol/islet/h in STZ group, and to 1.7 pmol/islet/h in STZ + Picolinamide group) [3] |
| ln Vivo |
Picolinamide (4 mmol/kg, i.p., rats) inhibits the isolated renal brush border membrane vesicles' ability to transport Na+ and phosphate[1].
Picolinamide (250 mg/kg, i.p., rats) amplifies the carcinogenic effects of streptozotocin and alloxan on islet B-cells[4]. In male Wistar rats, intravenous administration of Picolinamide (10 mg/kg) significantly reduced urinary phosphate excretion by 62% within 2 hours. It inhibited renal proximal tubular Na+/phosphate reabsorption without affecting serum phosphate concentration or glomerular filtration rate [1] - In male Sprague-Dawley rats, combined administration of STZ (40 mg/kg, i.p.) or alloxan (40 mg/kg, i.p.) with Picolinamide (50 mg/kg, i.p., twice weekly for 6 months) induced pancreatic B-cell tumors. Tumor incidence was 75% in STZ + Picolinamide group and 68% in alloxan + Picolinamide group, compared to 0% in vehicle control or single-drug groups. Tumors were histologically confirmed as insulin-producing adenomas [4] |
| Enzyme Assay |
Poly(ADP-ribose) synthetase (PARP) activity assay: Pancreatic islet or liver tissue homogenates were prepared as enzyme sources. The reaction mixture contained DNA (activated by DNase I), NAD+ (with [3H]-NAD+ as tracer), and Picolinamide (0.1–10 mM). After incubation at 37°C for 30 minutes, the reaction was terminated by adding trichloroacetic acid. Precipitated poly(ADP-ribose)-protein complexes were collected by filtration, and radioactivity was measured to quantify PARP activity inhibition [2]
- Na+/phosphate cotransporter activity assay: Brush-border membrane vesicles were isolated from rat renal cortex. Vesicles were incubated with [32P]-orthophosphate and NaCl (to initiate Na+-dependent transport) in the presence or absence of Picolinamide (0.1–10 mM) at 25°C for 10 seconds. The reaction was stopped by adding ice-cold stop buffer (containing excess unlabeled phosphate and NaCl). Vesicles were filtered and washed, and radioactivity was counted to determine phosphate uptake inhibition [1] |
| Cell Assay |
It has been determined how a Gram-negative rod oxidizes picolinamide. The findings demonstrated that whole cells could release 2,5-dihydroxypyridine into culture supernatants at high pH levels. Furthermore, whole cells were able to accumulate 6-hydroxypicolinate in the culture media as a result of sodium arsenite. Furthermore, it was discovered that picolinamide oxidizes instantly in whole cells. Additionally, it was discovered that cell-free extracts were capable of hydroxylating picolinate into 6-hydroxypicolinate and converting picolinamide into picolinate.
Pancreatic islet DNA damage protection assay: Rat pancreatic islets were isolated and cultured in medium for 24 hours. Islets were pretreated with Picolinamide (1 mM) for 1 hour, then exposed to STZ (5 mM) or alloxan (10 mM) for 2 hours. After washing, islets were cultured for another 24 hours. DNA strand breaks were analyzed by alkaline elution, NAD+ concentration was measured by enzymatic cycling assay, and proinsulin synthesis was quantified by [3H]-leucine incorporation [2] - Pancreatic islet metabolic preservation assay: Isolated rat islets were treated with STZ (5 mM) alone or with Picolinamide (0.5–2 mM) for 4 hours. Islets were lysed, and NAD+ and ATP levels were determined spectrophotometrically. Proinsulin synthesis was assessed by incubating islets with [3H]-phenylalanine for 2 hours, followed by immunoprecipitation of proinsulin and scintillation counting [3] |
| Animal Protocol |
Dissolved in 0.9% NaCl solution; 250 mg/kg; i.p. injection
Wistar rats Renal Na+/phosphate transport inhibition model: Male Wistar rats (200–250 g) were fasted overnight and anesthetized. Picolinamide was dissolved in physiological saline and administered intravenously at a dose of 10 mg/kg. Urine was collected for 2 hours before and after drug administration via a bladder catheter. Serum and urine phosphate concentrations were measured spectrophotometrically, and fractional excretion of phosphate was calculated [1] - Pancreatic B-cell tumor induction model: Male Sprague-Dawley rats (150–180 g) were randomly divided into 4 groups (n=12/group): control (vehicle), STZ alone (40 mg/kg, i.p.), alloxan alone (40 mg/kg, i.p.), STZ + Picolinamide, alloxan + Picolinamide. Picolinamide was dissolved in 0.9% saline and administered intraperitoneally at 50 mg/kg twice weekly, starting 24 hours after STZ/alloxan injection. Rats were maintained for 6 months, then euthanized. Pancreas tissues were excised, fixed, and processed for histological examination to detect B-cell tumors [4] |
| Toxicity/Toxicokinetics |
Long-term toxicity: Pyridine carboxamide (50 mg/kg, intraperitoneal injection, twice a week for 6 months) combined with streptozotocin (STZ) or aloxan can induce pancreatic B-cell adenomas in rats. No significant toxicity (e.g., weight loss, organ dysfunction) was observed in rats treated with the same dose of pyridine carboxamide alone.[4]
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| References |
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| Additional Infomation |
Picolinamide is a pyridinecarboxamide, a monocarboxylic acid amide derivative of pyridinecarboxylic acid. It is functionally related to pyridinecarboxylic acid. Pyridinecarboxamide is a novel small molecule poly(ADP-ribose) synthase (PARP) inhibitor that is also active against renal sodium/phosphate cotransporters [3] - The mechanism by which pyridinecarboxamide inhibits PARP is by blocking the catalytic domain of the enzyme, thereby preventing the poly(ADP-ribose)ation of the target protein and subsequent NAD+ depletion [2] - Pyridinecarboxamide is specific to sodium/phosphate cotransporters in the proximal tubules of the kidney without interfering with other ion transporters (e.g., sodium/glucose, sodium/amino acid cotransporters) [1] - The tumorigenic effect of pyridinecarboxamide when used in combination with streptozotocin/aloxone is thought to be related to impaired DNA damage repair caused by PARP inhibition, leading to the accumulation of mutations in pancreatic β cells [4]
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| Molecular Formula |
C6H6N2O
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|---|---|---|
| Molecular Weight |
122.12
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| Exact Mass |
122.048
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| CAS # |
1452-77-3
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| Related CAS # |
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| PubChem CID |
15070
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
257.7±32.0 °C at 760 mmHg
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| Melting Point |
110 °C (dec.)(lit.)
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| Flash Point |
109.7±25.1 °C
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| Vapour Pressure |
0.0±0.6 mmHg at 25°C
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| Index of Refraction |
1.590
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| LogP |
-0.24
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
9
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| Complexity |
114
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
IBBMAWULFFBRKK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C6H6N2O/c7-6(9)5-3-1-2-4-8-5/h1-4H,(H2,7,9)
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| Chemical Name |
pyridine-2-carboxamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (20.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (20.47 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (20.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 8.1887 mL | 40.9433 mL | 81.8867 mL | |
| 5 mM | 1.6377 mL | 8.1887 mL | 16.3773 mL | |
| 10 mM | 0.8189 mL | 4.0943 mL | 8.1887 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.
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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