Name: Pralsetinib (BLU-667)
Brand: Selleck Chemicals
SKU: S8716
Rating: 5 (7 reviews)

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).

Pralsetinib (BLU-667) Chemical Structure

CAS: 2097132-94-8

Selleck's Pralsetinib (BLU-667) has been cited by 7 publications

Purity & Quality Control

Batch: Purity: 99.99%

99.99

Pralsetinib (BLU-667) Related Products

Signaling Pathway

c-RET Signaling Pathway

Choose Selective c-RET Inhibitors

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)	Click to View More Targets
0.3 nM	0.4 nM	0.4 nM	0.4 nM	0.4 nM	Click to View More Targets

In vitro
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].
Kinase Assay	Human Kinase Selectivity
Kinase Assay	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	Cell lines	LC2/ad cells,　MZ-CRC-1 cells and TT cells
	Concentrations	0-1 μM
	Incubation Time	90 minutes
	Method	--

In Vivo
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].
Animal Research	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	--

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT04760288	Withdrawn	Medullary Thyroid Cancer	Hoffmann-La Roche	November 30 2023	Phase 3
NCT04697446	Unknown status	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 Diseases\|Carcinoma Bronchogenic\|Bronchial Diseases\|Head and Neck Neoplasms\|Carcinoma\|Neoplasms by Histologic Type\|Neoplasms Germ Cell and Embryonal\|Neoplasms Nerve Tissue\|Metastatic Non Small Cell Lung Cancer	Blueprint Medicines Corporation\|Analysis Group Inc.	December 1 2020	--
NCT03037385	Active not recruiting	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	Hoffmann-La Roche	March 17 2017	Phase 1\|Phase 2

References

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

Chemical Information & Solubility

Molecular Weight	533.60	Formula	C₂₇H₃₂FN₉O₂
CAS No.	2097132-94-8	SDF	--
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
Storage (From the date of receipt)	3 years -20°C powder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years -20°C powder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 100 mg/mL ( (187.4 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 13 mg/mL

Water : Insoluble

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In vivo
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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 μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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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

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