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

General Information of Drug (ID: DMS2J0Z)

• Drug Name: Pexidartinib Drug Info
• Synonyms: PLX-3397

Indication

Disease Entry	ICD 11	Status	REF
Tenosynovial giant cell tumour	2F7B	Approved	[1]
Alzheimer disease	8A20	Phase 3	[2]
Pigmented villonodular synovitis	FA27.1	Phase 3	[3]
Neurofibromatosis type 1	LD2D.10	Phase 1/2	[4]

• Cross-matching ID:
  PubChem CID: 25151352
  ChEBI ID: CHEBI:145373
  CAS Number: CAS 1029044-16-3
  TTD Drug ID: DMS2J0Z
  ACDINA Drug ID: D01339

Molecule-Related Drug Atlas

Drug(s) Targeting Macrophage colony-stimulating factor 1 receptor (CSF1R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sulfatinib	DMPOTM4	Neuroendocrine cancer	2B72.1	Phase 3	[6]
ARRY-382	DM0VGDC	Solid tumour/cancer	2A00-2F9Z	Phase 2	[6]
BLZ-945	DMG1LVA	Amyotrophic lateral sclerosis	8B60.0	Phase 2	[6]
Cabiralizumab	DMGE058	Pancreatic cancer	2C10	Phase 2	[7]
AMB-05X	DM958C5	Idiopathic pulmonary fibrosis	CB03.4	Phase 2	[8]
FPA-008	DM3ZN6Y	Autoimmune diabetes	5A10	Phase 1/2	[3]
DCC-3014	DMHW289	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[6]
DCC-3014	DMHW289	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[9]
PLX7486	DM0IVGU	Pancreatic cancer	2C10	Phase 1	[6]
TPX-0022	DMC2IJN	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]

Drug(s) Targeting Tyrosine-protein kinase Kit (KIT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[11]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[12]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[13]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[14]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[14]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[15]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[16]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[17]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]
MP470	DMELUAK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[19]

Drug(s) Targeting Fms-like tyrosine kinase 3 (FLT-3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[20]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[14]
Intedanib	DMSTA36	Colorectal cancer	2B91.Z	Approved	[21]
Midostaurin	DMI6E0R	Acute myeloid leukaemia	2A60	Approved	[11]
Gilteritinib	DMTI0ZO	Acute myeloid leukaemia	2A60	Approved	[22]
Pacritinib	DM1T6ZN	Myelofibrosis	2A20.2	Approved	[20]
Quizartinib	DM8Y4JS	Acute myeloid leukaemia	2A60	Approved	[6]
Lestaurtinib	DMQ2AIJ	Acute myeloid leukaemia	2A60	Approved (orphan drug)	[23]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[17]
BMS-690514	DMX302C	Chronic pain	MG30	Phase 2	[24]

Drug(s) Affected By Macrophage colony-stimulating factor 1 (CSF1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[25]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[26]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[27]
Selenium	DM25CGV	N. A.	N. A.	Approved	[28]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[29]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[30]
Nefazodone	DM4ZS8M	Major depressive disorder	6A70.3	Approved	[31]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[32]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[33]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[34]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fms-like tyrosine kinase 3 (FLT-3)	TTGJCWZ	FLT3_HUMAN	Inhibitor	[1]
Macrophage colony-stimulating factor 1 receptor (CSF1R)	TT7MRDV	CSF1R_HUMAN	Inhibitor	[1]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Macrophage colony-stimulating factor 1 (CSF1)	OT68M7RD	CSF1_HUMAN	Protein Interaction/Cellular Processes	[5]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [2] ClinicalTrials.gov (NCT02371369) PLX3397 Phase 3 Study for Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCT-TS). U.S. National Institutes of Health.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Antitumor activity of a pexidartinib bioisostere inhibiting CSF1 production and CSF1R kinase activity in human hepatocellular carcinoma. Chem Biol Interact. 2023 Jan 5;369:110255. doi: 10.1016/j.cbi.2022.110255. Epub 2022 Nov 9.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Clinical pipeline report, company report or official report of AmMax Bio
• [9] Clinical pipeline report, company report or official report of Deciphera Pharmaceuticals.
• [10] Clinical pipeline report, company report or official report of Turning Point Therapeutics.
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• [12] 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.
• [13] New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven a... J Med Chem. 2000 Jun 15;43(12):2310-23.
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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• [16] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [17] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [18] National Cancer Institute Drug Dictionary (drug id 452042).
• [19] Phase 1B study of amuvatinib in combination with five standard cancer therapies in adults with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Jul;74(1):195-204.
• [20] 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: 1807).
• [21] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [22] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [23] Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with ... Blood. 2008 Jun 15;111(12):5663-71.
• [24] Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2. J Pharm Sci. 2010 Aug;99(8):3579-93.
• [25] Gene expression profiles with activation of the estrogen receptor alpha-selective estrogen receptor modulator complex in breast cancer cells expressing wild-type estrogen receptor. Cancer Res. 2002 Aug 1;62(15):4419-26.
• [26] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
• [27] Enhanced production of nitric oxide by bone marrow cells and increased sensitivity to macrophage colony-stimulating factor (CSF) and granulocyte-macrophage CSF after benzene treatment of mice. Blood. 1994 Jun 1;83(11):3255-63.
• [28] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [29] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [30] 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.
• [31] Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury. Arch Toxicol. 2020 Apr;94(4):1151-1172. doi: 10.1007/s00204-020-02691-9. Epub 2020 Mar 10.
• [32] Alcohol and Cannabinoids Differentially Affect HIV Infection and Function of Human Monocyte-Derived Dendritic Cells (MDDC). Front Microbiol. 2015 Dec 22;6:1452. doi: 10.3389/fmicb.2015.01452. eCollection 2015.
• [33] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [34] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.