Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMBK9AM)

• Drug Name: PLX-4720 Drug Info
• Synonyms: PLX 4720; PLX4720 (BRAF inhibitor)

Indication

Disease Entry	ICD 11	Status	REF
Cutaneous melanoma	2C30	Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 24180719
  ChEBI ID: CHEBI:90295
  CAS Number: CAS 918505-84-7
  TTD Drug ID: DMBK9AM

Molecule-Related Drug Atlas

Drug(s) Targeting Vascular endothelial growth factor receptor 2 (KDR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[5]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[6]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[7]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[8]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[9]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[10]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[11]
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[12]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[13]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[14]

Drug(s) Targeting B-Raf messenger RNA (BRAF mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MLN2480	DMBR8NF	Solid tumour/cancer	2A00-2F9Z	Phase 2	[15]
RG7304	DMGFAVQ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[16]
SPN-803	DM8O2AQ	Parkinson disease	8A00.0	Phase 1	[15]
L-779450	DM51B74	Discovery agent	N.A.	Investigative	[17]
ZM-336372	DMD5JYQ	Discovery agent	N.A.	Investigative	[18]
PLX-ORI3	DMZG1L5	Solid tumour/cancer	2A00-2F9Z	Investigative	[15]
2-(Phenylamino)-6-(3-acetamidophenyl)pyrazine	DMPUARE	Discovery agent	N.A.	Investigative	[19]
ISIS 13741	DMC7Q38	Discovery agent	N.A.	Investigative	[20]
ISIS 14144	DMWIKD5	Discovery agent	N.A.	Investigative	[20]
PMID26061392C2	DMHZOIU	Discovery agent	N.A.	Investigative	[21]

Drug(s) Affected By Heat shock factor protein 1 (HSF1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[22]
SPI-1005	DM6XFHS	Reperfusion injury	ND56.Z	Approved	[4]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[4]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[23]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[24]
Ceftazidime	DM41GRA	Bacteremia	1A73	Approved	[4]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[25]
Chlorpheniramine	DM5URA2	Allergic rhinitis	CA08.0	Approved	[4]
Ethacrynic acid	DM60QMR	Edema	MG29	Approved	[4]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[4]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
B-Raf messenger RNA (BRAF mRNA)	TT0EOB8	BRAF_HUMAN	Inhibitor	[2]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Gene/Protein Processing	[4]

References

• [1] Targeting BRAFV600E with PLX4720 displays potent antimigratory and anti-invasive activity in preclinical models of human thyroid cancer. Oncologist. 2011;16(3):296-309.
• [2] Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011 Oct 30;29(11):1046-51.
• [3] In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res. 2003 Jan;9(1):327-37.
• [4] A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.
• [5] Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
• [6] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [8] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [9] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [10] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [11] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [12] Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther. 2014;15(12):1635-45.
• [13] Clinical pipeline report, company report or official report of Exelixis (2011).
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [15] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1943).
• [16] Clinical pipeline report, company report or official report of Roche.
• [17] The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2006 Jan 15;16(2):378-81.
• [18] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [19] Novel inhibitors of B-RAF based on a disubstituted pyrazine scaffold. Generation of a nanomolar lead. J Med Chem. 2006 Jan 12;49(1):407-16.
• [20] US patent application no. 5,981,731, Antisense oligonucleotide modulation of B-raf gene expression.
• [21] Photoactivatable Prodrugs of Antimelanoma Agent Vemurafenib. ACS Chem Biol. 2015 Sep 18;10(9):2099-107.
• [22] NRF2 transcriptionally activates the heat shock factor 1 promoter under oxidative stress and affects survival and migration potential of MCF7 cells. J Biol Chem. 2018 Dec 14;293(50):19303-19316. doi: 10.1074/jbc.RA118.003376. Epub 2018 Oct 11.
• [23] Non-steroidal anti-inflammatory drugs inhibit the expression of cytokines and induce HSP70 in human monocytes. Cytokine. 1999 May;11(5):347-58. doi: 10.1006/cyto.1998.0437.
• [24] Simvastatin induces heat shock factor 1 in vascular endothelial cells. Atherosclerosis. 2006 Oct;188(2):265-73. doi: 10.1016/j.atherosclerosis.2005.10.045. Epub 2005 Dec 20.
• [25] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.