| Size | Price | Stock | Qty |
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| Targets |
The primary target of trans-Pralsetinib is the rearranged during transfection (RET) receptor tyrosine kinase. RET is a proto-oncogene that plays a critical role in cell proliferation, differentiation, and survival. Activating mutations and fusions of RET are implicated in various cancers, including non-small cell lung cancer and medullary thyroid carcinoma. trans-Pralsetinib potently inhibits wild-type RET and clinically relevant RET mutants, including V804L, V804M, M918T, and CCDC6-RET fusions, with IC₅0 values ranging from 0.3 to 0.4 nM. This potent inhibition makes it a valuable tool for studying RET-driven cancers.
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| ln Vitro |
In vitro studies demonstrate that trans-Pralsetinib is a highly potent and selective RET inhibitor with IC₅0 values ranging from 0.3 to 0.4 nM for wild-type RET and four enzyme variants. The compound exhibits broad anti-tumor activity against multiple RET-driven solid tumor types. In cell-based assays, trans-Pralsetinib effectively inhibits RET phosphorylation and downstream signaling pathways, leading to reduced cell proliferation and increased apoptosis in RET-dependent cancer cells. Its potent and selective activity makes it a valuable research tool for studying RET biology and validating RET as a therapeutic target in various cancers.
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| ln Vivo |
In vivo studies of trans-Pralsetinib are focused on evaluating its antitumor efficacy in animal models of RET-driven cancers. As a highly potent and selective RET inhibitor with IC₅0 values of 0.3-0.4 nM, the compound is expected to demonstrate significant tumor growth inhibition in vivo. trans-Pralsetinib has been studied in xenograft models of RET-driven tumors, showing robust anti-tumor activity. The compound's oral bioavailability and favorable pharmacokinetic properties support its use in in vivo studies. Further studies are needed to fully characterize its efficacy, safety, and pharmacokinetic profile in various disease models.
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| Enzyme Assay |
For in vitro enzyme/receptor binding assays, trans-Pralsetinib is evaluated using kinase activity assays that measure RET phosphorylation. The compound is incubated with recombinant RET enzyme and ATP at various concentrations. RET kinase activity is quantified by measuring phosphorylation of peptide substrates using radiometric, fluorescence-based, or ELISA methods. IC₅0 values are determined from dose-response curves. Binding affinity to RET can be assessed using surface plasmon resonance (SPR) or other biophysical methods. Selectivity profiling against other kinases is performed to confirm specificity.
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| Cell Assay |
For in vitro cellular experiments, trans-Pralsetinib is tested in RET-dependent cancer cell lines, such as those harboring RET fusions or mutations. Cells are cultured in appropriate media and treated with various concentrations of the compound (typically ranging from picomolar to micromolar). RET phosphorylation and downstream signaling (such as MAPK and PI3K/AKT pathways) are assessed by Western blotting. Cell viability, proliferation, and apoptosis are evaluated using standard assays such as MTT, CellTiter-Glo, or flow cytometry. The compound's effects on cell cycle and migration can also be assessed.
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| Animal Protocol |
For in vivo animal experiments, trans-Pralsetinib can be administered to tumor-bearing mice via oral gavage, taking advantage of its oral bioavailability. Xenograft models using human RET-driven cancer cell lines in immunodeficient mice are commonly used to evaluate antitumor efficacy. Typical dosing regimens may range from 1 to 50 mg/kg administered daily or intermittently. Tumor volume is measured regularly, and tumor growth inhibition is calculated. Pharmacodynamic markers such as RET phosphorylation and downstream signaling are assessed in tumor tissues by Western blotting or immunohistochemistry. Body weight and overall health are monitored.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of trans-Pralsetinib include oral bioavailability, supporting its administration via oral gavage in vivo. The compound has favorable pharmacokinetic properties for a research compound, with reasonable absorption, distribution, metabolism, and excretion characteristics. Detailed parameters such as Cₘₐₓ, Tₘₐₓ, AUC, half-life, and clearance would need to be determined through comprehensive PK studies. The compound's molecular weight of 533.60 g/mol and chemical properties suggest it may have good tissue distribution and brain penetration. Formulation development may be optimized for in vivo studies.
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| Toxicity/Toxicokinetics |
Toxicological data for trans-Pralsetinib are limited, as it is primarily a research tool. As a potent RET inhibitor, its toxicity would depend on the importance of RET for normal cellular function. RET signaling is involved in various physiological processes, and its inhibition could have on-target effects. Comprehensive toxicology studies including acute and repeated-dose toxicity, genotoxicity, and cardiotoxicity assessments would be needed for further development. Appropriate safety precautions should be taken when handling this compound, including the use of personal protective equipment and adherence to institutional safety guidelines.
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| References |
Jason D. Brubaker, et al. Inhibitors of ret. US20170121312A1.; http://www.blueprintmedicines.com/wp-content/uploads/2017/10/BLU-667-EORTC-2017-BPM.pdf
[2]. Subbiah V, et al. Precision Targeted Therapy With BLU-667 for RET-Driven Cancers. American Association for Cancer Research. 10.1158/2159-8290.CD-18-0338.
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| Additional Infomation |
Pralsetinib is a kinase inhibitor. Its mechanism of action is as a transfection rearrangement (RET) inhibitor.
See also: Pralsetinib (note moved to). trans-Pralsetinib is a research compound used to study RET biology and develop therapies for RET-driven cancers. No clinical trials or regulatory approvals have been reported for this specific stereoisomer as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound is a highly potent and selective RET inhibitor with IC₅0 values of 0.3-0.4 nM and demonstrates broad anti-tumor activity against multiple RET-driven solid tumor types. It is the defined active stereoisomer of the clinical RET inhibitor pralsetinib. |
| Molecular Formula |
C27H32FN9O2
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|---|---|
| Molecular Weight |
533.600487709045
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| Exact Mass |
533.266
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| CAS # |
2097132-93-7
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| Related CAS # |
Pralsetinib;2097132-94-8
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| PubChem CID |
129073603
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
39
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| Complexity |
816
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC1C=NN(C=1)C1=CC=C(C=N1)[C@H](C)NC(C1(CCC(C2N=C(C=C(C)N=2)NC2C=C(C)NN=2)CC1)OC)=O
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| InChi Key |
GBLBJPZSROAGMF-SIYOEGHHSA-N
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| InChi Code |
InChI=1S/C27H32FN9O2/c1-16-11-22(33-23-12-17(2)35-36-23)34-25(31-16)19-7-9-27(39-4,10-8-19)26(38)32-18(3)20-5-6-24(29-13-20)37-15-21(28)14-30-37/h5-6,11-15,18-19H,7-10H2,1-4H3,(H,32,38)(H2,31,33,34,35,36)/t18-,19?,27?/m0/s1
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| Chemical Name |
N-[(1S)-1-[6-(4-fluoropyrazol-1-yl)pyridin-3-yl]ethyl]-1-methoxy-4-[4-methyl-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]cyclohexane-1-carboxamide
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| Synonyms |
trans-Blu667trans-Blu 667trans-Blu-667
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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 : ~100 mg/mL (~187.41 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.55 mg/mL (8.53 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 45.5 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 (4.69 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8741 mL | 9.3703 mL | 18.7406 mL | |
| 5 mM | 0.3748 mL | 1.8741 mL | 3.7481 mL | |
| 10 mM | 0.1874 mL | 0.9370 mL | 1.8741 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.
Link: https://clinicaltrials.gov/ct2/show/NCT04589845
Conditions:Solid TumorsLink: https://clinicaltrials.gov/ct2/show/NCT06563999
Conditions:Lung Cancer Stage III|MutationLink: https://clinicaltrials.gov/ct2/show/NCT04302025
Conditions:Non-small Cell Lung Cancer
Title:A Study of Pralsetinib Versus Standard of Care for First-Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)
Status:Terminated
updateDate:2026-03-05
Ctid:NCT04222972
Link: https://clinicaltrials.gov/ct2/show/NCT04222972
Conditions:RET-fusion Non Small Cell Lung Cancer|Lung Neoplasm|Carcinoma, Non-Small-Cell Lung|Respiratory Tract Neoplasms|Thoracic Neoplasms|Neoplasms by Site|Neoplasms|Lung Diseases|Respiratory Tract Disease|Carcinoma, Bronchogenic|Bronchial Diseases|Head and Neck Neoplasms|Adenocarcinoma|Carcinoma|Neoplasms by Histologic Type|Neoplasms, Germ Cell and Embryonal|Neoplasms, Nerve TissueLink: https://clinicaltrials.gov/ct2/show/NCT07418879
Conditions:Non-small Cell Lung Cancer|RET Fusion|PralsetinibLink: https://clinicaltrials.gov/ct2/show/NCT07010393
Conditions:Thyroid NeoplasmsLink: https://clinicaltrials.gov/ct2/show/NCT03037385
Conditions:RET-altered Non Small Cell Lung Cancer|Medullary Thyroid Cancer|RET-altered Papillary Thyroid Cancer|RET-altered Colon Cancer|RET-altered Solid Tumors|Lung Neoplasm|Carcinoma, Non-Small-Cell Lung|Thyroid Diseases|Thyroid Neoplasm|Thyroid Cancer, Papillary|Carcinoma, Neuroendocrine|Respiratory Tract Neoplasms|Thoracic Neoplasms|Neoplasms by Site|Neoplasms|Lung Diseases|Respiratory Tract Disease|Carcinoma, Bronchogenic|Bronchial Neoplasms|Endocrine System Diseases|Endocrine Gland Neoplasm|Head and Neck Neoplasms|Adenocarcinoma, Papillary|Adenocarcinoma|Carcinoma|Neoplasms, Glandular and Epithelial|Neoplasms by Histologic Type|Neuroendocrine Tumors|Neuroectodermal Tumors|Neoplasms, Germ Cell and Embryonal|Neoplasms, Nerve Tissue|Colonic Neoplasms|Colorectal Neoplasms|Intestinal Neoplasms|Gastrointestinal Neoplasms|Digestive System Neoplasm|Digestive System Disease|Gastrointestinal Disease|Colonic Diseases|Intestinal DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT05525858
Conditions:Solid Tumor|Advanced Solid Tumor|Metastatic CancerLink: https://clinicaltrials.gov/ct2/show/NCT04632992
Conditions:Advanced Unresectable or Metastatic Solid MalignancyLink: https://clinicaltrials.gov/ct2/show/NCT06482086
Conditions:Locally Advanced Thyroid Gland CarcinomaLink: https://clinicaltrials.gov/ct2/show/NCT04760288
Conditions:Medullary Thyroid CancerLink: https://clinicaltrials.gov/ct2/show/NCT04591431
Conditions:Breast Cancer|Gastrointestinal Cancer|Non Small Cell Lung Cancer|Other CancerLink: https://clinicaltrials.gov/ct2/show/NCT04204928
Conditions:Non-Small Cell Lung Cancer|Medullary Thyroid CancerProducts are for research use only; We do not sell to patients
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