Physicochemical Properties
| Molecular Formula | C26H38CLN5O8 |
| Molecular Weight | 584.0616 |
| Exact Mass | 583.24 |
| CAS # | 2443966-86-5 |
| Related CAS # | Macropa-NH2 TFA;2705054-08-4;Macropa-NH2 diester;2146091-22-5;Macropa-NCS;2146095-31-8 |
| PubChem CID | 138911411 |
| Appearance | White to off-white solid powder |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 13 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 40 |
| Complexity | 700 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | Cl[H].O1C([H])([H])C([H])([H])OC([H])([H])C([H])([H])N(C([H])([H])C2C([H])=C([H])C([H])=C(C(=O)O[H])N=2)C([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])N(C([H])([H])C2C([H])=C(C([H])=C(C(=O)O[H])N=2)N([H])[H])C([H])([H])C1([H])[H] |
| InChi Key | LFFSSMKPBQSWNZ-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C26H37N5O8.ClH/c27-20-16-22(29-24(17-20)26(34)35)19-31-6-10-38-14-12-36-8-4-30(5-9-37-13-15-39-11-7-31)18-21-2-1-3-23(28-21)25(32)33;/h1-3,16-17H,4-15,18-19H2,(H2,27,29)(H,32,33)(H,34,35);1H |
| Chemical Name | 4-amino-6-[[16-[(6-carboxypyridin-2-yl)methyl]-1,4,10,13-tetraoxa-7,16-diazacyclooctadec-7-yl]methyl]pyridine-2-carboxylic acid;hydrochloride |
| Synonyms | Macropa-NH2 hydrochloride; Macropa-NH2 (hydrochloride); 2443966-86-5; 4-amino-6-[[16-[(6-carboxypyridin-2-yl)methyl]-1,4,10,13-tetraoxa-7,16-diazacyclooctadec-7-yl]methyl]pyridine-2-carboxylic acid;hydrochloride; |
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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
| Targets | Prostate-specific membrane antigen |
| ln Vitro | Prior to the gradual addition of CSCl2 (305 µL of CSCl2, 85%, Acros Organics), a white suspension of 11·4TFA (0.1598 g, 0.16 mmol) and Na2CO3 (0.2540 g, 2.4 mmol) was heated at reflux in acetone (10 mL) for 30 minutes. The orange suspension that resulted was heated at reflux for three hours before being reduced to a pale orange solid and concentrated at 30 °C under reduced pressure. After portioning the material into 10% ACN/H2O with 0.2% TFA (8 mL total), filtering it, and purifying it right away using preparative HPLC, Method C was used. The pure fractions were mixed, concentrated at room temperature under decreased pressure to eliminate the organic solvent, and lyophilized. Fractions at -80 °C were frozen if they could not be concentrated right away. After being obtained as a mixture of white and pale-yellow solid (0.0547 g), isothiocyanate 12 was kept in a jar of Drierite at a temperature of –80 °C. A 0.1 M pH 9.1 NaHCO3 buffer containing 0.154 M NaCl was used to generate a stock solution containing 4.4 mg/mL of macropa-NCS, which was then kept at -80 °C. Macropa-NCS (52 μL) and NaHCO3 buffer (266 μL) were added to a portion of Tmab in saline (74 μL), resulting in final concentrations of Tmab and macropa-NCS of 5.1 mg/mL and 0.59 mg/mL, respectively. Based on the tetra-TFA salt's molecular weight of 1045.76 g/mol, macropa-NCS was shown to be 16 times more molar than Tmab[1]. |
| ln Vivo | The 18-membered macrocycle H2 macropa was investigated for 225 Ac chelation in targeted alpha therapy (TAT). Radiolabeling studies showed that macropa, at submicromolar concentration, complexed all 225 Ac (26 kBq) in 5 min at RT. [225 Ac(macropa)]+ remained intact over 7 to 8 days when challenged with either excess La3+ ions or human serum, and did not accumulate in any organ after 5 h in healthy mice. A bifunctional analogue, macropa-NCS, was conjugated to trastuzumab as well as to the prostate-specific membrane antigen-targeting compound RPS-070. Both constructs rapidly radiolabeled 225 Ac in just minutes at RT, and macropa-Tmab retained >99 % of its 225 Ac in human serum after 7 days. In LNCaP xenograft mice, 225 Ac-macropa-RPS-070 was selectively targeted to tumors and did not release free 225 Ac over 96 h. These findings establish macropa to be a highly promising ligand for 225 Ac chelation that will facilitate the clinical development of 225 Ac TAT for the treatment of soft-tissue metastases [1]. |
| References |
[1]. An Eighteen-Membered Macrocyclic Ligand for Actinium-225 Targeted Alpha Therapy. Angew Chem Int Ed Engl. 2017 Nov 13;56(46):14712-14717. |
Solubility Data
| Solubility (In Vitro) |
H2O: ≥ 100 mg/mL (171.22 mM) DMSO: 83.33 mg/mL (142.67 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.56 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 20.8 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: ≥ 2.08 mg/mL (3.56 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 20.8 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: ≥ 2.08 mg/mL (3.56 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7122 mL | 8.5608 mL | 17.1215 mL | |
| 5 mM | 0.3424 mL | 1.7122 mL | 3.4243 mL | |
| 10 mM | 0.1712 mL | 0.8561 mL | 1.7122 mL |