Pidotimod (PGT-1A) is an oral immunomodulator/immunostimulant and a synthetic dipeptide with immunomodulatory properties against adaptive and the innate immune systems. Also able to increase the concentration of salivary IgA directed against bacteria. Pidotimod increases macrophage activity and humoral immune functions, and can be used for chronic bronchitis, chronic obstructive pulmonary disease (COPD), bronchiectasis, and chronic idiopathic urticaria.
Physicochemical Properties
| Molecular Formula | C9H12N2O4S |
| Molecular Weight | 244.2676 |
| Exact Mass | 244.051 |
| Elemental Analysis | C, 44.25; H, 4.95; N, 11.47; O, 26.20; S, 13.13 |
| CAS # | 121808-62-6 |
| PubChem CID | 65944 |
| Appearance | Solid powder |
| Density | 1.5±0.1 g/cm3 |
| Boiling Point | 663.0±55.0 °C at 760 mmHg |
| Melting Point | 194-198ºC (dec.) |
| Flash Point | 354.8±31.5 °C |
| Vapour Pressure | 0.0±4.3 mmHg at 25°C |
| Index of Refraction | 1.619 |
| LogP | -2.38 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 16 |
| Complexity | 346 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | S1C([H])([H])N(C([C@]2([H])C([H])([H])C([H])([H])C(N2[H])=O)=O)[C@]([H])(C(=O)O[H])C1([H])[H] |
| InChi Key | UUTKICFRNVKFRG-WDSKDSINSA-N |
| InChi Code | InChI=1S/C9H12N2O4S/c12-7-2-1-5(10-7)8(13)11-4-16-3-6(11)9(14)15/h5-6H,1-4H2,(H,10,12)(H,14,15)/t5-,6-/m0/s1 |
| Chemical Name | (R)-3-((S)-5-Oxopyrrolidine-2-carbonyl)thiazolidine-4-carboxylic acid |
| Synonyms | Pidotomod; PGT/1A; PGT 1A; PGT1A; PGT-1A; |
| 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 Vivo | Pidotimod (oral gavage; 800 mg/kg; 12 months) was found to be harmless to rats and 600 mg/kg to dogs in animal toxicology investigations. Pidotimod has no effect on embryonic and fetal development in rats (up to 1000 mg/kg/day), nor does it have any teratogenic effects when administered orally at 600 mg/kg or intravenously at 1000 mg/kg. It also has no effect on the perinatal or postnatal phase. no harmful repercussions after childbirth. Rat (orally 600 mg/kg) [1]. Pidotimod (ip; 200 mg/kg; 5 days) increased the activity of natural killer (NK) cells, the reaction to concanavalin A (ConA), and the proliferation of leukocytes in response to mitogens like interleukin 2. IL-2)[2]. In methylprednisolone-induced immunosuppressed mice, pidotimod (ip; 10-100 mg/kg) markedly boosts macrophage superoxygenation and normalizes the depletion of peritoneal macrophage numbers [2]. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Bioavailability of 45%. 95% of intravenous dose is eliminated in the urine as the parent compound. Biological Half-Life Half life of 4 h. |
| References |
[1]. Ashok Mahashur, et al. Pidotimod: In-depth review of current evidence. Lung India [2]. Ning Zhao, et al. Pidotimod: a review of its pharmacological features and clinical effectiveness in respiratory tract infections. Expert Rev Anti Infect Ther. 2019 Oct;17(10):803-818. |
| Additional Infomation |
(4R)-3-[oxo-[(2S)-5-oxo-2-pyrrolidinyl]methyl]-4-thiazolidinecarboxylic acid is a peptide. Pidotimod is a synthetic dipeptide with immunomodulatory properties. Drug Indication For use as immunostimulant therapy for treatment of cell-mediated immunosuppression with respiratory or urinary infections. Mechanism of Action Pidotimod inhibits tumor necrosis factor α (TNF-α) induced increases in extracellular signal-related kinase (ERK) phosphorylation. It also increases nuclear factor κB (NFκB) expression and translocation to the nucleus. It is these to modulatory effects on ERK and NFκB signalling which are thought to produce the increase in toll-like receptor expression seen with pidotimod. Pidotimod increase maturation of dendritic cells responsible for presenting antigens to naive Th-cells. It also appears to result in a greater population these cells diiferentiating to Th1 cells which are believed to mediate the immune response to pathogens like bacteria and viruses. Lastly, pidotimod appears to increase antigen-specific antibody titer and cytotoxic response with antigen exposure. The precise mechanism and timeline of events leading to these effects is unknown. |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~409.38 mM) H2O : ~25 mg/mL (~102.35 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.23 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 (10.23 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (10.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. Solubility in Formulation 4: 14.29 mg/mL (58.50 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0938 mL | 20.4692 mL | 40.9383 mL | |
| 5 mM | 0.8188 mL | 4.0938 mL | 8.1877 mL | |
| 10 mM | 0.4094 mL | 2.0469 mL | 4.0938 mL |