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

General Information of Drug (ID: DMK2XB7)

• Drug Name: AR-00341677 Drug Info
• Synonyms: GDC-0879; Anticancer program, Array/Genentech; B-Raf kinase inhibitors (cancer), Array/Genentech

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 25093303
  ChEBI ID: CHEBI:91434
  CAS Number: CAS 905281-76-7
  TTD Drug ID: DMK2XB7

Molecule-Related Drug Atlas

Drug(s) Targeting Serine/threonine-protein kinase B-raf (BRAF)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dabrafenib	DMX6OE3	Melanoma	2C30	Approved	[5]
Vemurafenib	DM62UG5	Melanoma	2C30	Approved	[6]
LGX818	DMNQXV8	Melanoma	2C30	Approved	[7]
PLX8394	DMRTD7I	Solid tumour/cancer	2A00-2F9Z	Phase 2	[8]
CEP-32496	DMAO04B	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[9]
BGB-283	DMVYTG7	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[10]
ARQ 736	DMP9ZT1	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
RO-5212054	DML4C3Q	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
ASN003	DMJCX6D	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]
BMS-908662	DM3K8VM	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]

Drug(s) Affected By Tissue factor (F3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[15]
Primidone	DM0WX6I	Epilepsy	8A60-8A68	Approved	[4]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[16]
Dactinomycin	DM2YGNW	Adult kidney Wilms tumor		Approved	[17]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[18]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[19]
Fructose	DM43AN2	Vomiting	MD90	Approved	[20]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[21]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[4]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[22]

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	[23]
SPI-1005	DM6XFHS	Reperfusion injury	ND56.Z	Approved	[3]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[3]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[24]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[25]
Ceftazidime	DM41GRA	Bacteremia	1A73	Approved	[3]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[26]
Chlorpheniramine	DM5URA2	Allergic rhinitis	CA08.0	Approved	[3]
Ethacrynic acid	DM60QMR	Edema	MG29	Approved	[3]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[3]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Serine/threonine-protein kinase B-raf (BRAF)	TTWCGQT	BRAF_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Gene/Protein Processing	[3]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Gene/Protein Processing	[4]

References

• [1] 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. (Ligand id: 5681).
• [2] 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. (Ligand id: 5681).
• [3] 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.
• [4] Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects. Int J Mol Sci. 2015 Jan 5;16(1):1008-29. doi: 10.3390/ijms16011008.
• [5] Clinical pipeline report, company report or official report of GlaxoSmithKline (2011).
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [7] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [8] Identification of PLX4032-resistance mechanisms and implications for novel RAF inhibitors. Pigment Cell Melanoma Res. 2014 Mar;27(2):253-62.
• [9] Clinical pipeline report, company report or official report of Ambit Biosciences.
• [10] BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF-Mutated Colorectal Cancers. Mol Cancer Ther. 2015 Oct;14(10):2187-97.
• [11] National Cancer Institute Drug Dictionary (drug id 688029).
• [12] National Cancer Institute Drug Dictionary (drug id 680347).
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] Clinical pipeline report, company report or official report of Exelixis (2011).
• [15] Inhibition of interleukin-1-induced endothelial tissue factor expression by the synthetic cannabinoid WIN 55,212-2. Oncotarget. 2016 Sep 20;7(38):61438-61457. doi: 10.18632/oncotarget.11367.
• [16] The effects of chemotherapeutic agents on the regulation of thrombin on cell surfaces. Br J Haematol. 2003 Jan;120(2):315-24. doi: 10.1046/j.1365-2141.2003.03971.x.
• [17] Mechanisms of tissue factor induction by the uremic toxin indole-3 acetic acid through aryl hydrocarbon receptor/nuclear factor-kappa B signaling pathway in human endothelial cells. Arch Toxicol. 2019 Jan;93(1):121-136.
• [18] Simvastatin attenuates vascular hypercoagulability in cardiac transplant recipients. Transplantation. 2000 May 15;69(9):1830-6. doi: 10.1097/00007890-200005150-00017.
• [19] Resveratrol and quercetin down-regulate tissue factor expression by human stimulated vascular cells. J Thromb Haemost. 2003 May;1(5):1089-95. doi: 10.1046/j.1538-7836.2003.00217.x.
• [20] Non-nutritional sweeteners effects on endothelial vascular function. Toxicol In Vitro. 2020 Feb;62:104694. doi: 10.1016/j.tiv.2019.104694. Epub 2019 Oct 23.
• [21] Tissue factors on acute promyelocytic leukemia and endothelial cells are differently regulated by retinoic acid, arsenic trioxide and chemotherapeutic agents. Leukemia. 1999 Jul;13(7):1062-70. doi: 10.1038/sj.leu.2401448.
• [22] Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
• [23] 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.
• [24] 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.
• [25] 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.
• [26] 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.