Name: Tovorafenib (MLN2480)
Brand: Selleck Chemicals
SKU: S7121
Availability: InStock
Rating: 5 (7 reviews)

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Quality Control

Batch: Purity: 99.94%

99.94

Related Targets	ERK p38 MAPK JNK MEK Ras KRas S6 Kinase MAP4K TAK1 Mixed Lineage Kinase
Other Raf Inhibitors	LY3009120 Exarafenib (KIN-2787) GDC-0879 Avutometinib (Ro5126766, CH5126766) PLX-4720 AZ 628 SB590885 TAK-632 GW5074 RAF265 (CHIR-265)

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Activity Description	PMID
A673	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
SK-N-SH	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
NB1643	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (197.51 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

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Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

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Calculation results:

Working concentration: mg/ml;

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.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	506.29	Formula	C₁₇H₁₂Cl₂F₃N₇O₂S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1096708-71-2	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	BIIB-024, TAK580, AMG-2112819, BSK1369, DAY-101			Smiles	CC(C1=NC=C(S1)C(=O)NC2=NC=C(C(=C2)C(F)(F)F)Cl)NC(=O)C3=C(C(=NC=N3)N)Cl

Mechanism of Action

Targets/IC₅₀/Ki	Raf
In vitro	Tovorafenib (MLN2480) inhibits MAPK pathway signaling in BRAF mutant and some RAS mutant preclinical cancer models at concentrations that are tolerated in vivo. It is found to activate phosphorylated MEK at very low concentrations, but inhibits this same activity at higher concentrations. The inhibitory effects of this compound are found to vary across models and genetic contexts. In vitro analysis of the drug combination of MLN2480 and TAK-733 (an investigational allosteric MEK kinase inhibitor) in cell proliferation assays demonstrates synergistic activity. In addition, western blot analysis demonstrates the effect of it in reversing feedback activation of MEK in response to TAK-733, leading to more concerted MAPK pathway inhibition. It only modestly inhibits PRAK.
In vivo	In vivo, Tovorafenib (MLN2480) shows antitumor activity in melanoma, colon, lung, and pancreatic cancer xenograft models. This compound (37.5 mg/kg) is well tolerated in a tumor xenograft model. The combination of it (12.5 mg) and TAK-733 (1 mg/kg) is effective in an SK-MEL-30 xenograft model, but monotherapy with either compound produces negligible effects.
References	[1] http://hwmaint.meeting.ascopubs.org/cgi/content/abstract/31/15_suppl/e13529 [2] https://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=2&p_RefId=1820866&p_IsPs=N [3] http://meetinglibrary.asco.org/content/109770-132 [4] https://pubmed.ncbi.nlm.nih.gov/26671150/ [5] https://pubmed.ncbi.nlm.nih.gov/28002790/

Applications

Methods	Biomarkers	Images	PMID
Western blot	p-ERK / ERK		28082416

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT06381570	Recruiting	Low-grade Glioma	Daniel Morgenstern\|The Hospital for Sick Children	March 21 2024	Early Phase 1
NCT05566795	Recruiting	Low-grade Glioma	Day One Biopharmaceuticals Inc.\|SIOPe Brain Tumor Group LOGGIC Consortium	February 27 2023	Phase 3
NCT04985604	Recruiting	Melanoma\|Solid Tumor\|CRAF Gene Amplification\|RAF1 Gene Amplification\|BRAF Gene Fusion\|BRAF Fusion\|CRAF Gene Fusion\|CRAF Fusion\|RAF1 Gene Fusion\|RAF1 Fusion\|Thyroid Cancer Papillary\|Spitzoid Melanoma\|Pilocytic Astrocytoma\|Pilocytic Astrocytoma Adult\|Non Small Cell Lung Cancer\|Non-Small Cell Adenocarcinoma\|Colorectal Cancer\|Pancreatic Acinar Carcinoma\|Spitzoid Malignant Melanoma\|Bladder Cancer\|Bladder Urothelial Carcinoma\|MAP Kinase Family Gene Mutation\|RAS Mutation\|RAF Mutation\|MEK Mutation	Day One Biopharmaceuticals Inc.	July 15 2021	Phase 1\|Phase 2
NCT04775485	Recruiting	Low-grade Glioma\|Advanced Solid Tumor	Day One Biopharmaceuticals Inc.\|Pacific Pediatric Neuro-Oncology Consortium	April 22 2021	Phase 2
NCT03429803	Active not recruiting	Low-grade Glioma	Karen D. Wright MD\|PLGA Fund at Pediatric Brain Tumor Foundation\|National Cancer Institute (NCI)\|Pacific Pediatric Neuro-Oncology Consortium\|Team Jack Foundation\|Day One Biopharmaceuticals Inc.\|Dana-Farber Cancer Institute	February 27 2018	Phase 1

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Tovorafenib (MLN2480) Raf Kinase Inhibitor

Chemical Structure

Molecular Weight: 506.29