| Size | Price | Stock | Qty |
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| 500 μg |
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Purity: ≥98%
Pentixafor is a ligand/intermediate used for the preparation of gallium Ga 68-pentixafor, which is a ligand for chemokine receptor C-X-C chemokine receptor type 4 (CXCR4), and a radioconjugate consisting a cyclic pentapeptide analog of stromal-cell derived factor-1 (SDF-1 or CXCL12).
Pentixafor (international nonproprietary name: Gallium (⁶⁸Ga) boclatixafortide) is a cyclic pentapeptide analog targeting the C-X-C motif chemokine receptor type 4 (CXCR4), first developed in 2011 by Professor Wester and colleagues at the Technical University of Munich, Germany. As a synthetic analog of stromal cell-derived factor-1 (SDF-1, also known as CXCL12), Pentixafor binds to CXCR4 with high affinity (nanomolar range) and high specificity. Typically radiolabeled with ⁶⁸Ga to form [⁶⁸Ga]Ga-Pentixafor, this tracer enables non-invasive visualization of CXCR4 expression levels in vivo via positron emission tomography (PET) imaging. CXCR4 is highly overexpressed in hematologic malignancies such as multiple myeloma and certain lymphomas, as well as in adrenal disorders like primary aldosteronism, making [⁶⁸Ga]Ga-Pentixafor PET/CT of significant clinical value for diagnosis, staging, and prognostic assessment of these diseases. The tracer features rapid renal clearance, optimal imaging at approximately 60 minutes post-injection, a low effective radiation dose (approximately 2.3 mSv per 150 MBq), and a favorable safety profile. Pentixafor has received orphan drug designation from the European Medicines Agency and is currently in Phase III clinical development for the diagnosis of multiple myeloma.| Targets |
CXCR4/chemokine receptor C-X-C chemokine receptor type 4
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| ln Vitro |
A growing body of literature reports on the upregulation of C-X-C motif chemokine receptor 4 (CXCR4) in a variety of cancer entities, rendering this receptor as suitable target for molecular imaging and endoradiotherapy in a theranostic setting. For instance, the CXCR4-targeting positron emission tomography (PET) agent [68 Ga]PentixaFor has been proven useful for a comprehensive assessment of the current status quo of solid tumors, including adrenocortical carcinoma or small-cell lung cancer. In addition, [68 Ga]PentixaFor has also provided an excellent readout for hematological malignancies, such as multiple myeloma, marginal zone lymphoma, or mantle cell lymphoma. PET-based quantification of the CXCR4 capacities in vivo allows for selecting candidates that would be suitable for treatment using the theranostic equivalent [177Lu]/[90Y]PentixaTher. This CXCR4-directed theranostic concept has been used as a conditioning regimen prior to hematopoietic stem cell transplantation and to achieve sufficient anti-lymphoma/-tumor activity in particular for malignant tissues that are highly sensitive to radiation, such as the hematological system. Increasing the safety margin, pretherapeutic dosimetry is routinely performed to determine the optimal activity to enhance therapeutic efficacy and to reduce off-target adverse events[1].
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| ln Vivo |
In mice affected with either CXCR4( −) or CXCR4( +) leukemia xenografts, an increased [68Ga]PentixaFor signal was observed in the latter animals [1].
After intravenous administration, [177Lu]PentixaTher binds to plasma proteins with high metabolic stability, and only a small fraction of about 4% is attached to leukocytes and platelets via CXCR4 binding. Scintigraphically detectable activity accumulations are found in kidney, liver, spleen, and bone marrow, as well as in CXCR4-expressing malignant tissues. An example of measured time functions of activity retention in organs and tissues in a patient with MM is shown in Fig. 5. The figure, like the results summarized below unless otherwise specified, is taken from a recently published study on [177Lu]PentixaTher biokinetics and dosimetry.[1] |
| Enzyme Assay |
Biokinetics and pretherapeutic dosimetry[1]
After intravenous administration, [177Lu]PentixaTher binds to plasma proteins with high metabolic stability, and only a small fraction of about 4% is attached to leukocytes and platelets via CXCR4 binding. Scintigraphically detectable activity accumulations are found in kidney, liver, spleen, and bone marrow, as well as in CXCR4-expressing malignant tissues. An example of measured time functions of activity retention in organs and tissues in a patient with MM is shown in Fig. 5. The figure, like the results summarized below unless otherwise specified, is taken from a recently published study on [177Lu]PentixaTher biokinetics and dosimetry. |
| Animal Protocol |
Aiming to provide a roadmap among a broad spectrum of neoplasms, a recent bicentric study assessed [68Ga]PentixaFor uptake and image contrast among the largest cohort of subjects imaged with CXCR4-directed PET to date, thereby determining the most relevant clinical applications. Investigating 690 patients affected with various solid tumors and hematological neoplasms scheduled for 777 scans, 68.9% demonstrated uptake in sites of disease The highest tracer uptake was recorded in MM (maximum SUV > 12). The second highest uptake was then found in ACC, MCL, adrenocortical adenoma, and SCL. Osteosarcoma, bladder cancer, head and neck cancer, and Ewing sarcoma, on the other hand, exhibited the lowest average SUV (< 6; Fig. 4A). Comparable findings were recorded for target-to-background ratio (TBR), thereby reflecting image contrast. Again, the highest TBR was found in advanced blood cancers, including MM, MCL, and acute lymphoblastoid leukemia (Fig. 4B). Moreover, lower specific activity is characterized by higher amounts of cold mass, thereby having a relevant impact on image interpretation. The authors did not record any relevant significant associations with semiquantitative parameters and specific activity, supporting the hypothesis that read-out capabilities are not hampered, regardless of the amount of specific activities[1].
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| ADME/Pharmacokinetics |
Systemic 177Lu activity typically decays in a biexponential manner. Approximately half of the activity is excreted primarily by the kidneys, with a median effective half-life of approximately 10 hours; the remainder decays with an average effective half-life of approximately 4 days. The blood concentration of activity typically comprises three fractions, with approximately 10%, 2.5%, and 0.2% of the administered activity per liter of blood decaying with half-lives of 0.23 hours, 7 hours, and 40 hours, respectively. PentixaTher accumulates in the bone marrow and remains there for several days, making the bone marrow the primary organ for acute toxicity. Calculated bone marrow specific doses are heterogeneous, ranging from 0.14 to 2.3 (median 0.5) Gy/GBq 177Lu. Given the significant individual variability and the uncertainty in bone marrow dosing, the therapeutic use of PentixaTher may be limited to myeloablative therapy. However, in myeloablative therapy, it must be considered that the long-term retention of radiopharmaceuticals in the bone marrow means that a long decay time is required before stem cell transplantation. Therefore, in order to shorten the period of aplastic impairment and reduce the risk of related complications, 90Y is usually used instead of 177Lu for treatment[1].
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| Toxicity/Toxicokinetics |
Toxicity Overview [1]
To investigate safety, we included 22 patients with advanced hematologic malignancies who received [177Lu] or [90Y] PentixaTher followed by chemotherapy and then hematopoietic stem cell transplantation (HSCT). As expected, all patients experienced cytopenia (including decreases in hemoglobin, white blood cells, granulocytes, and platelets; Figure 7A). One patient developed tumor lysis syndrome, which subsequently led to grade 3 acute renal failure, while all other adverse events were manageable and did not cause delays in subsequent treatment. In this respect, the time interval between CXCR4 ERT and pretreatment was significantly longer in the [177Lu] PentixaTher group than in the [90Y] PentixaTher group, which is likely due to the longer half-life of [177Lu] PentixaTher (6.7 days) compared to [90Y] PentixaTher (2.7 days; Figure 7B). The ongoing COLPRIT trial is a prospective phase I/II study that will further clarify the efficacy and safety of this treatment and diagnostic strategy in patients with advanced hematologic malignancies (Eudra-CT 2015-001817-28). |
| References | |
| Additional Infomation |
CXCR4 is highly expressed in a variety of cancer cells, making it a potential target for tumor detection and treatment strategies. The CXCR4-targeting PET imaging agent [68Ga]PentixaFor has been successfully used in patients with solid tumors and advanced hematologic malignancies, showing significant radiotracer accumulation in adenoid cystic carcinoma (ACC), small cell lung cancer (SCLC), multiple myeloma (MM), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), or gastric mucosa-associated lymphoid tissue (MALT). In addition to assessing the broad distribution of the disease, this functional imaging approach can also evaluate the function of the target in vivo. Therefore, quantitative analysis of [68Ga]PentixaFor accumulation can be used to evaluate the efficacy of non-radioactive CXCR4 inhibitor therapy (e.g., treatment of MM patients with anti-human CXCR4 IgG monoclonal antibodies) or to identify patients suitable for treatment with CXCR4-targeting diagnostic radiotracers (e.g., [177Lu]/[90Y]PentixaTher). The latter concept has been applied to known radiation-sensitive hematologic malignancies, such as advanced multiple myeloma (MM), acute lymphoblastic leukemia (ALL), or diffuse large B-cell lymphoma. In this context, pre-treatment dosimetry can determine the appropriate dose required to achieve antitumor effects and minimize off-target effects. CXCR4 ERT also resulted in the expected bone marrow clearance and has therefore been included in the treatment regimens for patients with advanced hematologic malignancies (CXCR4 ERT followed by allogeneic/autologous hematopoietic stem cell transplantation, which was successful). These treatment regimens have shown significant efficacy and have greatly benefited patients who have previously received extensive treatment. Due to the high intratumoral dose, some patients have developed tumor lysis syndrome, and these patients should be closely monitored [1].
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| Molecular Formula |
C60H80N14O14
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|---|---|
| Molecular Weight |
1221.36261367798
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| Exact Mass |
1220.597
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| Elemental Analysis |
C, 59.00; H, 6.60; N, 16.06; O, 18.34
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| CAS # |
1341207-62-2
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| Related CAS # |
1341207-62-2;1342253-77-3 (Gallium);1345698-96-5 (Ga-68);
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| PubChem CID |
54575322
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| Appearance |
White to off-white solid powder
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| LogP |
-6.3
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| Hydrogen Bond Donor Count |
12
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| Hydrogen Bond Acceptor Count |
19
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| Rotatable Bond Count |
23
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| Heavy Atom Count |
88
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| Complexity |
2330
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CN1[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](C1=O)CC2=CC=C(C=C2)O)CC3=CC4=CC=CC=C4C=C3)CCCN=C(N)N)CCCNC(=O)C5=CC=C(C=C5)CNC(=O)CN6CCN(CCN(CCN(CC6)CC(=O)O)CC(=O)O)CC(=O)O
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| InChi Key |
OSUJVKAXNLHVRB-HUMWUIFSSA-N
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| InChi Code |
nChI=1S/C60H80N14O14/c1-70-49(9-5-20-63-55(84)43-16-10-40(11-17-43)33-65-51(77)35-71-22-24-72(36-52(78)79)26-28-74(38-54(82)83)29-27-73(25-23-71)37-53(80)81)58(87)68-46(8-4-21-64-60(61)62)57(86)69-47(32-41-12-15-42-6-2-3-7-44(42)30-41)56(85)66-34-50(76)67-48(59(70)88)31-39-13-18-45(75)19-14-39/h2-3,6-7,10-19,30,46-49,75H,4-5,8-9,20-29,31-38H2,1H3,(H,63,84)(H,65,77)(H,66,85)(H,67,76)(H,68,87)(H,69,86)(H,78,79)(H,80,81)(H,82,83)(H4,61,62,64)/t46-,47-,48+,49+/m0/s1
SMILES Code: OC1=CC=C(C[C@@H](NC(CNC([C@H](CC2=CC3=C(C=CC=C3)C=C2)NC4=O)=O)=O)C(N(C)[C@H](CCCNC(C5=CC=C(CNC(CN6CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC6)=O)C=C5)=O)C(N[C@H]4CCCNC(N)=N)=O)=O)C=C1
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| Chemical Name |
2,2',2''-(10-(2-((4-((3-((2R,5S,8S,14R)-5-(3-guanidinopropyl)-14-(4-hydroxybenzyl)-1-methyl-8-(naphthalen-2-ylmethyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentaazacyclopentadecan-2-yl)propyl)carbamoyl)benzyl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid
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| Synonyms |
CPCR 4-2; CPCR4-2; CPCR-4-2; CPCR42; CPCR4-2; TOZ93UY3AX; UNII-TOZ93UY3AX; 2-[4,7-bis(carboxymethyl)-10-[2-[[4-[3-[(2R,5S,8S,14R)-5-[3-(diaminomethylideneamino)propyl]-14-[(4-hydroxyphenyl)methyl]-1-methyl-8-(naphthalen-2-ylmethyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]propylcarbamoyl]phenyl]methylamino]-2-oxoethyl]-1,4,7,10-tetrazacyclododec-1-yl]acetic acid; (68GA)PENTIXAFOR; BOCLATIXAFORTIDE; Ligand of gallium Ga 68-pentixafor; CPCR-42; CPCR 42; Pentixafor
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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 Note: Please store this product in a sealed and protected environment, away from moisture and light. |
| 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: ~100 mg/mL (81.9 mM)
Methanol: ≥ 125 mg/mL (102.3 mM) |
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8188 mL | 4.0938 mL | 8.1876 mL | |
| 5 mM | 0.1638 mL | 0.8188 mL | 1.6375 mL | |
| 10 mM | 0.0819 mL | 0.4094 mL | 0.8188 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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