| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Somatostatin type 2 (SST2) receptor
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| ln Vitro |
Acromegaly is a hormonal disorder associated with excessive secretion of growth hormone (GH) and subsequent increase in the production of insulin-like growth factor I (IGF-I). Similar to the natural hormone somatostatin, paltusotine suppresses GH and IGF-1 secretion. Paltusotine exerts its pharmacological activity via selective agonism (>4000-fold) at somatostatin receptor 2 (SSTR2) and exhibits little or no affinity for other SST receptor subtypes. Paltusotine inhibited cyclic adenosine monophosphate accumulation via human SSTR2 activation with an average drug (agonist) concentration that results in half-maximal response (EC50) of 0.25 nM.
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| ln Vivo |
Paltusotine, a somatostatin receptor agonist, reduces IGF-1 levels in acromegaly patients in a dose-dependent manner across the 20 to 60 mg therapeutic dose range. Paltusotine may inhibit gallbladder contractility and decrease bile secretion, potentially leading to gallbladder stones or sludge. Paltusotine can also cause changes in glucose metabolism, potentially resulting in hyperglycemia or, less commonly, hypoglycemia. Somatostatin analogs, including paltusotine, may suppress thyroid-stimulating hormone secretion, potentially leading to hypothyroidism. Additionally, they can inhibit pancreatic enzyme and bile acid secretion, potentially causing malabsorption of dietary fats and steatorrhea. Decreased vitamin B12 levels have also been observed.
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| ADME/Pharmacokinetics |
Absorption
In healthy subjects, pertuzumab exposure increased proportionally with increasing dose, ranging from 20 mg (lowest approved recommended dose) to 120 mg (twice the highest approved recommended dose). In patients with acromegaly, a significant dose-proportional increase in mean steady-state trough concentration was also observed with a once-daily dose of 60 mg. Steady-state exposure of pertuzumab is reached within one week after once-daily administration. The geometric mean absolute bioavailability of 20 mg pertuzumab as an oral solution is 69%, with little inter-individual variability. The median time to reach maximum plasma concentration (Tmax) after oral administration of pertuzumab is 1 to 4 hours, regardless of the duration of fasting. Food decreases the drug's AUC and Cmax. Excretion The primary route of excretion after oral administration of radiolabeled pertuzumab is fecal excretion, with total radioactive recoveries observed in feces (90%) and urine (3.9%). Unmetabolized pertuzumab is the main component of excrement. Volume of Distribution The volume of distribution (Vz) of pertuzumab is 220 L. Clearance The geometric mean (geometric coefficient of variation %CV) of the apparent oral clearance (CL/F) after a single oral dose of 20 mg pertuzumab is 8.4 (27.1) L/h. Protein Binding Pertuzumab has a high plasma protein binding rate (99%). Metabolism/Metabolites Pertuzumab is primarily metabolized in the liver. The primary metabolic pathway is glucuronidation, mainly catalyzed by UGT1A1 and UGT1A9 enzymes. The secondary pathway is oxidation, mainly catalyzed by CYP3A4/5, with less catalytic activity from CYP2D6. Four metabolites (M632/1, M472/1, M648/1, and M676/1) have been identified, with their main metabolic pathways being glucuronidation, monooxidation, and N-carbamoylglucuronidation. Biological Half-Life After reaching maximum concentration, the concentration of pertuxotine decreases, with an apparent terminal half-life of 28 hours. |
| Toxicity/Toxicokinetics |
Safety Information
Palsonify increases the risk of gallstones, hyperglycemia, hypoglycemia, bradycardia, thyroid dysfunction, steatorrhea, malabsorption of dietary fat, and changes in vitamin B12 levels. The most common side effects include diarrhea, abdominal pain, nausea, decreased appetite, bradycardia, hyperglycemia, and gastroenteritis. Dosage and Administration The recommended starting dose is 40 mg orally once daily with water on an empty stomach, at least 6 hours after a meal (i.e., after an overnight fast) and at least 1 hour before the next meal. During initial treatment, the dose of palsonify may be temporarily reduced to 20 mg once daily if necessary, depending on tolerance. Once adverse reactions subside, patients should resume the dose of 40 mg palsonify once daily. After 2 to 4 weeks of taking palsonify 40 mg once daily, patients may be advised to increase the dose to 60 mg once daily, depending on their IGF-1 levels. |
| References |
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| Additional Infomation |
Pertuxotine is being investigated in the clinical trial NCT04261712 (ACROBAT Advance), a study evaluating the long-term safety and efficacy of pertuxotine in the treatment of acromegaly. Pertuxotine is an orally bioavailable non-peptide somatostatin receptor type 2 (SST2) agonist with potential growth hormone (GH) secretion inhibition and antitumor activity. After oral administration, pertuxotine targets, binds to, and activates SSTR2, thereby inhibiting the secretion of human growth hormone (hGH) from the pituitary gland and leading to a reduction in the production of insulin-like growth factor (IGF-1). This may inhibit IGF-1-mediated cell signaling pathways and lead to apoptosis. Some neuroendocrine tumor cells overexpress SSTR2, while GH is excessively secreted in the pituitary gland of patients with acromegaly.
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| Molecular Formula |
C27H22F2N4O
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|---|---|
| Molecular Weight |
456.4866
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| Exact Mass |
456.176
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| Elemental Analysis |
C, 71.04; H, 4.86; F, 8.32; N, 12.27; O, 3.50
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| CAS # |
2172870-89-0
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| Related CAS # |
2172870-89-0; 2361216-83-1 (HCl); 2172875-40-8 (2HCl)
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| PubChem CID |
134168328
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| Appearance |
White to yellow solid powder
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| LogP |
5.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
34
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| Complexity |
727
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C([H])=C(C([H])=C(C=1[H])C1=C([H])N=C2C([H])=C([H])C(C3=C([H])C([H])=C([H])C(C#N)=C3O[H])=C([H])C2=C1N1C([H])([H])C([H])([H])C([H])(C([H])([H])C1([H])[H])N([H])[H])F
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| InChi Key |
GHILNKWBALQPDP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H22F2N4O/c28-19-10-18(11-20(29)13-19)24-15-32-25-5-4-16(22-3-1-2-17(14-30)27(22)34)12-23(25)26(24)33-8-6-21(31)7-9-33/h1-5,10-13,15,21,34H,6-9,31H2
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| Chemical Name |
3-[4-(4-aminopiperidin-1-yl)-3-(3,5-difluorophenyl)quinolin-6-yl]-2-hydroxybenzonitrile
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| Synonyms |
Paltusotine; 2172870-89-0; CRN00808; Paltusotine [INN]; CRN-00808;
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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) |
DMSO: 20 mg/mL (43.81 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.48 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 2: ≥ 2 mg/mL (4.38 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 20.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1906 mL | 10.9531 mL | 21.9063 mL | |
| 5 mM | 0.4381 mL | 2.1906 mL | 4.3813 mL | |
| 10 mM | 0.2191 mL | 1.0953 mL | 2.1906 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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