Pralsetinib (BLU-667)

Name: Pralsetinib (BLU-667)
Brand: Selleck Chemicals
SKU: S8716
Rating: 5 (1 reviews)

For research use only.

Catalog No.S8716

1 publication

Pralsetinib (BLU-667) Chemical Structure

Molecular Weight(MW): 533.60

Pralsetinib (BLU-667) is a highly potent and selective 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).

Selleck's Pralsetinib (BLU-667) has been cited by 1 publication

Mol Cancer Res, 2020, 27;molcanres.1245.2019

PubMed: 32461304

Purity & Quality Control

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Biological Activity

Description

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	View More

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

Kinase Assay: ^[1]	- Collapse 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 Research: ^[1]	- Collapse Cell lines: LC2/ad cells,　MZ-CRC-1 cells and TT cells Concentrations: 0-1 μM Incubation Time: 90 minutes Method: -- (Only for Reference)
Animal Research: ^[1]	- Collapse 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: -- (Only for Reference)

References

[1] Subbiah V, et al. Cancer Discov. 2018, 8(7):836-849.

Solubility (25°C)

In vitro	DMSO	100 mg/mL (187.4 mM)
	Water	Insoluble
	Ethanol	'''100 mg/mL

* 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.

Chemical Information

Molecular Weight	533.60
Formula	C₂₇H₃₂FN₉O₂
CAS No.	2097132-94-8
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CC1=CC(=NN1)NC2=NC(=NC(=C2)C)C3CCC(CC3)(C(=O)NC(C)C4=CN=C(C=C4)N5C=C(C=N5)F)OC

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Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid 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 DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2020-09-01)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03037385	Recruiting	Drug: pralsetinib (BLU-667)	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 Disease	Blueprint Medicines Corporation	March 17 2017	Phase 1\|Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Pralsetinib (BLU-667)