Home MAPK Raf inhibitor Tovorafenib (MLN2480)

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Tovorafenib (MLN2480) Raf inhibitor

Tovorafenib (MLN2480), also known as BIIB-024, TAK580, AMG-2112819, BSK1369, or DAY-101, is an oral, selective pan-Raf kinase inhibitor in clinical trials.

Tovorafenib (MLN2480) Raf inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 506.29

Purity & Quality Control

Related Products

Signaling Pathway

Raf Signaling Pathways

Raf Signaling Pathway

Cell Culture and Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation 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

Mechanism of Action

Targets
Raf [1]

In vitro
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[1].

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[2].

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[1][2].
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-ERK / ERK S7121-WB1 28082416

In Vivo
In vivo

In vivo, Tovorafenib (MLN2480) shows antitumor activity in melanoma, colon, lung, and pancreatic cancer xenograft models[3]. It is well tolerated in a tumor xenograft model at 37.5 mg/kg. The combination of this compound (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[2].
Animal Research Animal Models C57BL/6J mice
Dosages 12.5 mg/kg
Administration oral gavage
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

References
  • http://hwmaint.meeting.ascopubs.org/cgi/content/abstract/31/15_suppl/e13529
  • https://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=2&p_RefId=1820866&p_IsPs=N
  • http://meetinglibrary.asco.org/content/109770-132
  • https://pubmed.ncbi.nlm.nih.gov/26671150/
  • https://pubmed.ncbi.nlm.nih.gov/28002790/

Chemical Information

Molecular Weight 506.29 Formula

C17H12Cl2F3N7O2S
CAS No. 1096708-71-2 SDF Download SDF
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

Storage and Stability

Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (197.51 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble


Molecular Weight Calculator

In vivo
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In vivo Formulation Calculator

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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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