Pralsetinib (BLU-667)

Catalog No.S8716 Batch:S871602

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Technical Data

Formula

C27H32FN9O2
Molecular Weight 533.60 CAS No. 2097132-94-8
Solubility (25°C)* In vitro DMSO 100 mg/mL (187.4 mM)
Ethanol 10 mg/mL (18.74 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Pralsetinib (BLU-667, CS 3009, Gavreto) is a highly potent and selective RET (c-RET) inhibitor with an IC50 of 0.4 nM for WT RET. It also demonstrates potent activity (IC50 0.4 nmol/L) against common oncogenic RET alterations, including RET (M918T).
Targets
RET V804L [1]
(Cell-free assay )		 WT RET [1]
(Cell-free assay)		 RET V804M [1]
(Cell-free assay)		 RET M918T [1]
(Cell-free asssay)		 CCDC6-RET [1]
(Cell-free assay)		 View More
0.3 nM 0.4 nM 0.4 nM 0.4 nM 0.4 nM
In vitro

BLU-667 is at least 100-fold more selective for RET over 96% of kinases tested (a panel of 371 kinases). BLU-667 specifically abrogates RET signaling in RET-altered cancers from diverse lineages. RET pathway inhibition with BLU-667 also more potently inhibits proliferation of RET-altered cell lines relative to multikinase inhibitors[1].
In vivo

In vivo, BLU-667 potently inhibits growth of NSCLC and thyroid cancer xenografts driven by various RET mutations and fusions without inhibiting VEGFR2. BLU-667 is well tolerated throughout the in vivo studies[1].

Protocol (from reference)

Kinase Assay:

[1]
  • Human Kinase Selectivity

    BLU-667 is screened at 300 nmol/L for inhibitory activity across a panel of 371 kinases. The 23 kinases inhibited >50% at 300 nmol/L are selected for full 10 point concentration-response curves with BLU-667 (1 μmol/L maximum concentration) at 200 μmol/L ATP to generate biochemical IC50 (Reaction Biology Corp) using 33P-ATP (10 mCi/mL) to initiate the reaction, followed by the detection of kinase activity by a filter-binding method.
Cell Assay:

[1]
  • Cell lines

    LC2/ad cells,　MZ-CRC-1 cells and TT cells

  • Concentrations

    0-1 μM

  • Incubation Time

    90 minutes

  • Method

    --
Animal Study:

[1]
  • Animal Models

    PDX tumor models (BALB/c nude mice)

  • Dosages

    3, 10, or 30 mg/kg twice daily or 60 mg/kg once daily

  • Administration

    --

Selleck's Pralsetinib (BLU-667) has been cited by 9 publications

Lenvatinib enhances antitumor immunity by promoting the infiltration of TCF1+ CD8+ T cells in HCC via blocking VEGFR2 [ Cancer Sci, 2023, 114(4):1284-1296] PubMed: 36609997
Lenvatinib enhances antitumor immunity by promoting the infiltration of TCF1+ CD8+ T cells in HCC via blocking VEGFR2 [ Cancer Sci, 2023, 114(4):1284-1296] PubMed: 36609997
Loss of Tumour Suppressor TMEM127 Drives RET-mediated Transformation Through Disrupted Membrane Dynamics [ bioRxiv, 2023, 2023.06.28.546955] PubMed: 37425958
Novel Calcium-Binding Ablating Mutations Induce Constitutive RET Activity and Drive Tumorigenesis [ Cancer Res, 2022, 82(20):3751-3762] PubMed: 36166639
The kinase PLK1 promotes the development of Kras/Tp53-mutant lung adenocarcinoma through transcriptional activation of the receptor RET [ Sci Signal, 2022, 15(754):eabj4009] PubMed: 36194647
Targeting RET Kinase in Neuroendocrine Prostate Cancer [ Mol Cancer Res, 2020, 18(8):1176-1188] PubMed: 32461304
Elucidating the Mechanism of RET Kinase Activity in Neuroendocrine Prostate Cancer [ Mol Cancer Res, 2020, 1176-1188] PubMed: None
Targeting RET Kinase in Neuroendocrine Prostate Cancer [ Mol Cancer Res, 2020, 27;molcanres.1245.2019] PubMed: 32461304
RET Kinase Signaling as a Key Switch Toward the Neuroendocrine Phenotype [ Defense Technical Information Center, 2020, N/A] PubMed: N/A

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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