| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg | |||
| Other Sizes |
Purity: ≥98%
Vipivotide tetraxetan (also known as PSMA-617) is a novel and highly potent prostate-specific membrane antigen (PSMA) inhibitor with anticancer activity. It inhibits PSMA with a Ki of 0.37 nM. Vipivotide tetraxetan is a ligand used to make 177Lu-PSMA-617 [Pluvicto (lutetium (177Lu) vipivotide tetraxetan)], which is a radioactive molecule approved in 2022 to combat cancer. PSMA-617 originally was developed at the German Cancer Research Center and the Heidelberg University Hospital. ABX held the exclusive license to bring the treatment through early clinical development.
| Targets |
Traditional Cytotoxic Agents
Prostate-Specific Membrane Antigen (PSMA) (Ki = 2.34 ± 2.94 nM on LNCaP cells; Ki = 0.37 ± 0.21 nM in enzymatic NAALADase assay) |
|---|---|
| ln Vitro |
For a minimum of 72 hours, pipivotide tetraxetan (PSMA-617) exhibits high radiolytic stability. It is shown to have a high inhibition potency (equilibrium dissociation constant Ki=2.34±2.94 nM on LNCaP; determined enzymatically to be Ki=0.37±0.21 nM) and to internalize into LNCaP cells very efficiently[1].
PSMA-617 demonstrated high binding affinity for PSMA with a Ki of 2.34 ± 2.94 nM on LNCaP cells and a subnanomolar Ki of 0.37 ± 0.21 nM in an enzyme-based NAALADase assay using recombinant human PSMA. The radiolabeled compounds [⁶⁸Ga]Ga-PSMA-617 and [¹⁷⁷Lu]Lu-PSMA-617 were efficiently internalized into PSMA-positive LNCaP cells, with internalization values of 17.67 ± 4.34 %IA/10⁶ cells and 17.51 ± 3.99 %IA/10⁶ cells, respectively, at 37°C. The binding affinity of the non-labeled compound and its radiolabeled counterparts ([⁶⁸Ga]Ga-PSMA-617 and [¹⁷⁷Lu]Lu-PSMA-617) was comparable, with Ki values of 6.40 ± 1.02 nM and 6.91 ± 1.32 nM, respectively. [⁶⁸Ga]Ga-PSMA-617 and [¹⁷⁷Lu]Lu-PSMA-617 exhibited high radiochemical stability in PBS and human serum for up to 72 hours at 37°C, with minimal release of free radionuclide. The lipophilicity (log D) of [⁶⁸/⁶⁷Ga]Ga-PSMA-617 was determined to be -2.00 in an n-octanol/HEPES buffer system. Serum protein binding analysis by gel filtration showed no significant transfer of activity to human serum proteins after 1 hour incubation at 37°C. [1] |
| ln Vivo |
After 1 hour (n = 3), organ distribution with 68Ga-labeled Vipivotide tetraxetan (PSMA-617) reveals a high specific uptake in the kidneys and LNCaP tumors. By coinjecting 2 mg of 2-PMPA per kilogram, the high uptake in the kidneys is almost entirely blocked. Except for the spleen, other organs like the liver, lung, and spleen exhibit relatively low absorption and no blocking effect.At one hour following injection, the tumor-to-background ratios are 7.8 (tumor to blood) and 17.1 (tumor to muscle). The organ distribution of 177Lu-labeled Vipivotide tetraxetan (PSMA-617) (n=3) demonstrates a similar uptake in the kidneys and LNCaP tumors as compared to the 68Ga-labeled version. It is discovered that the liver uptake differs statistically. Tumor-to-background ratios measured one hour after injection reveal somewhat higher values than the prior organ distribution with 68Ga-labeled Vipivotide tetraxetan (PSMA-617)[1]. Tumor to blood is 22.1, and tumor to muscle is 25.6.
In LNCaP tumor-bearing BALB/c nu/nu mice, [⁶⁸Ga]Ga-PSMA-617 showed specific uptake in tumors (8.47 ± 4.09 %ID/g at 1 h p.i.) and kidneys (113.3 ± 24.4 %ID/g at 1 h p.i.), which could be significantly blocked by co-injection of the PSMA inhibitor 2-PMPA. [¹⁷⁷Lu]Lu-PSMA-617 exhibited similar tumor uptake (11.20 ± 4.17 %ID/g at 1 h p.i.) and high kidney uptake (137.2 ± 77.8 %ID/g at 1 h p.i.), also blockable by 2-PMPA. The kidney uptake of [¹⁷⁷Lu]Lu-PSMA-617 cleared rapidly over time, decreasing from 137.2 ± 77.8 %ID/g at 1 h p.i. to 2.13 ± 1.36 %ID/g at 24 h p.i., while tumor uptake remained high (10.58 ± 4.50 %ID/g at 24 h p.i.). This favorable pharmacokinetic profile resulted in very high tumor-to-background ratios at 24 hours post-injection: tumor/blood = 1,058 and tumor/muscle = 529. Dynamic µPET imaging in mice showed high tumor-to-muscle contrast (ratio of 8.5) as early as 1 hour post-injection, rapid kidney excretion, and accumulation of radioactivity in the bladder within minutes. [1] |
| Enzyme Assay |
A competitive enzyme-based (NAALADase) assay was performed to determine the inhibition potency of PSMA-617 against recombinant human PSMA (rhPSMA). The assay is based on the competition between the non-labeled inhibitor and the enzyme's substrate. The concentration resulting in 50% inhibition (IC₅₀) was determined, and the inhibition constant (Ki) was calculated from the IC₅₀ value. [1]
|
| Cell Assay |
A cell-based competitive binding assay was conducted using PSMA-positive LNCaP cells to determine the binding affinity (Ki) of PSMA-617. Cells were incubated with a fixed concentration of a competing radioligand and varying concentrations of the unlabeled test compound. The bound radioactivity was measured, and data were analyzed using nonlinear regression to obtain the Ki value.
An internalization assay was performed to evaluate the cellular uptake of radiolabeled PSMA-617 ([⁶⁸Ga]Ga-PSMA-617 and [¹⁷⁷Lu]Lu-PSMA-617). LNCaP cells were incubated with the radioligand at 37°C. After specific time points, the surface-bound radioactivity was removed by an acid wash, and the internalized radioactivity (cell lysate) was measured using a gamma counter. Results were expressed as percentage of incubated activity (%IA) per 10⁶ cells. [1] |
| Animal Protocol |
For in vivo studies, 8-week-old male BALB/c nu/nu mice were subcutaneously inoculated into the right flank with 5 × 10⁶ LNCaP cells suspended in 50% Matrigel. Experiments commenced when tumors reached approximately 1 cm³ in size.
For µPET imaging, mice received an intravenous tail vein injection of approximately 30 MBq (0.5 nmol) of [⁶⁸Ga]Ga-PSMA-617. A 50-minute dynamic scan followed by a static scan from 100 to 120 minutes post-injection was performed. For biodistribution studies, mice received an intravenous tail vein injection of approximately 1 MBq (0.06 nmol) of either [⁶⁸/⁶⁷Ga]Ga-PSMA-617 or [¹⁷⁷Lu]Lu-PSMA-617. Animals were sacrificed at specified time points (1, 4, and 24 hours post-injection). Organs and blood were collected, weighed, and their radioactivity was measured using a gamma counter. Uptake was expressed as percentage of injected dose per gram of tissue (%ID/g). Specificity of uptake was confirmed in separate groups of mice by co-injecting 2 mg/kg of the PSMA inhibitor 2-PMPA along with the radioligand. [1] |
| ADME/Pharmacokinetics |
Biodistribution studies in tumor-bearing mice (LNCaP) showed that [⁶⁸Ga]Ga-PSMA-617 had a rapid blood clearance rate and was mainly excreted by the kidneys. Initial renal uptake was high, but it was rapidly cleared over time. One hour after injection, the renal uptake of [¹⁷⁷Lu]Lu-PSMA-617 was 137.2 ± 77.8 %ID/g, which decreased significantly to 2.13 ± 1.36 %ID/g 24 hours after injection, indicating high renal clearance efficiency. Tumor uptake continued for 24 hours, resulting in an excellent tumor-to-background ratio 24 hours after injection (tumor/blood: 1058; tumor/muscle: 529). [1]
|
| Toxicity/Toxicokinetics |
In a preliminary clinical diagnostic study, a single intravenous injection of 288 MBq (2 µg) of [⁶⁸Ga]Ga-PSMA-617 into one patient did not result in any adverse reactions or clinically detectable pharmacological effects. [1]
|
| References | |
| Additional Infomation |
PSMA-617 is a custom-designed, low-molecular-weight, therapeutic radiopharmaceutical composed of three components: a glutamate-urea-lysine pharmacophore (a PSMA inhibitor), a naphthyl-containing linker, and a chelating agent, DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). The DOTA chelator stably complexes with both diagnostic and therapeutic radiometals (⁶⁸Ga) and therapeutic radiometals (¹⁷⁷Lu, ⁹⁰Y), enabling true therapeutic integration using the same target molecule. The optimized linker is designed to improve tumor targeting, internalization efficiency, and pharmacokinetics, particularly accelerating renal clearance. This compound exhibits high radiochemical yields (⁶⁸/⁶⁷Ga-labeled yield >97%) (¹⁷⁷Lu-labeled purity >99%) and good stability.
A first-ever human PET/CT imaging study showed that prostate cancer metastases could be clearly visualized one hour after injection, with high tumor uptake and high contrast between the tumor and the background. [1] |
| Molecular Formula |
C49H71N9O16
|
|---|---|
| Molecular Weight |
1042.1388
|
| Exact Mass |
1,041.50
|
| Elemental Analysis |
C, 56.47; H, 6.87; N, 12.10; O, 24.56
|
| CAS # |
1702967-37-0
|
| Related CAS # |
1702967-37-0;PSMA617 TFA;
|
| PubChem CID |
122706786
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
11
|
| Hydrogen Bond Acceptor Count |
20
|
| Rotatable Bond Count |
27
|
| Heavy Atom Count |
74
|
| Complexity |
1870
|
| Defined Atom Stereocenter Count |
3
|
| InChi Key |
JBHPLHATEXGMQR-LFWIOBPJSA-N
|
| Chemical Name |
(((S)-1-carboxy-5-((S)-3-(naphthalen-2-yl)-2-((1r,4S)-4-((2-(4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)acetamido)methyl)cyclohexane-1-carboxamido)propanamido)pentyl)carbamoyl)-L-glutamic acid tetra(trifluoroacetic acid)
|
| Synonyms |
PSMA-617; WHO 11010; PSMA617; WHO-11010; PSMA 617; WHO11010;
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~119.95 mM)
H2O : ≥ 100 mg/mL (~95.96 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (2.00 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 (2.00 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (2.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10% DMSO+ 40% PEG300+ 5% Tween-80+ 45% saline: ≥ 2.08 mg/mL (2.00 mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9596 mL | 4.7978 mL | 9.5956 mL | |
| 5 mM | 0.1919 mL | 0.9596 mL | 1.9191 mL | |
| 10 mM | 0.0960 mL | 0.4798 mL | 0.9596 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05682443 | RECRUITING | Drug: ONC-392 | Metastatic Castration- resistant Prostate Cancer |
OncoC4, Inc. | 2023-12-11 | Phase 1 Phase 2 |
| NCT05803941 | RECRUITING | Drug: AAA617 | Prostate Cancer | Novartis Pharmaceuticals | 2023-08-14 | Phase 4 |
| NCT05849298 | RECRUITING | Drug: AAA617 Drug: AAA517 Drug: Piflufolastat F 18 |
Prostatic Neoplasm | Novartis Pharmaceuticals | 2024-01-03 | Phase 2 |
| NCT06099093 | RECRUITING | Drug: 18F-DCFPyl | Prostate Cancer | Brigham and Women's Hospital | 2024-04-01 | Phase 4 |
| NCT05658003 | ACTIVE | Drug: [177Lu]Lu-PSMA-617 Drug: ARDT Drug: [68Ga]Ga-PSMA-11 Other: Best supportive care |
Metastatic Castration-Resistant Prostate Cancer (mCRPC) |
Novartis Pharmaceuticals | 2023-05-05 | Phase 2 |
|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
