Details of the Drug

General Information of Drug (ID: DMS2J0Z)

• Drug Name: Pexidartinib
• 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]

• Affected Organisms: Humans and other mammals
• ATC Code:
  L01EX15: Pexidartinib
  L01EX: Other protein kinase inhibitors
  L01E: PROTEIN KINASE INHIBITORS
  L01: ANTINEOPLASTIC AGENTS
  L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 417.8
  Logarithm of the Partition Coefficient (xlogp); 4.5
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 7
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 77465 mcgh/L [5]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 8625 mcg/L [5]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2.5 h [5]
  Clearance: The clearance of drug is 5.1 L/h [5]
  Elimination: Pexidartinib is predominantly excreted via feces, where fecal excretion accounts for 65% of total pexidartinib elimination [5]
  Half-life: The concentration or amount of drug in body reduced by one-half in 26.6 hours [5]
  Metabolism: The drug is metabolized via the hepatic CYP3A4 and glucuronidation by UGT1A4 [5]
  Vd: The volume of distribution (Vd) of drug is 187 L [5]
• Chemical Identifiers:
  Formula: C20H15ClF3N5
  IUPAC Name: 5-[(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-N-[[6-(trifluoromethyl)pyridin-3-yl]methyl]pyridin-2-amine
  Canonical SMILES: C1=CC(=NC=C1CC2=CNC3=C2C=C(C=N3)Cl)NCC4=CN=C(C=C4)C(F)(F)F
  InChI: InChI=1S/C20H15ClF3N5/c21-15-6-16-14(10-28-19(16)29-11-15)5-12-2-4-18(26-7-12)27-9-13-1-3-17(25-8-13)20(22,23)24/h1-4,6-8,10-11H,5,9H2,(H,26,27)(H,28,29)
  InChIKey: JGWRKYUXBBNENE-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 25151352
  ChEBI ID: CHEBI:145373
  CAS Number: 1029044-16-3
  UNII: 6783M2LV5X
  DrugBank ID: DB12978
  TTD ID: D09TAB
  ACDINA ID: D01339
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

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	[6]

Molecular Expression Atlas of This Drug

• The Studied Disease: Tenosynovial giant cell tumour
• ICD Disease Classification: 2F7B

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Tyrosine-protein kinase Kit (KIT)	DTT	KIT	2.06E-01	-0.1	-0.14
Fms-like tyrosine kinase 3 (FLT-3)	DTT	FLT3	2.11E-01	-0.05	-0.16

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Pexidartinib (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Pexidartinib and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[7]
Tagraxofusp	DM9HQ5U	Major	Increased risk of hepatotoxicity by the combination of Pexidartinib and Tagraxofusp.	Acute myeloid leukaemia [2A60]	[8]
Oliceridine	DM6MDCF	Major	Increased metabolism of Pexidartinib caused by Oliceridine mediated induction of CYP450 enzyme.	Acute pain [MG31]	[9]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Pexidartinib caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[8]
Fenofibric acid	DMGO2MC	Major	Increased risk of hepatotoxicity by the combination of Pexidartinib and Fenofibric acid.	Cardiovascular disease [BA00-BE2Z]	[8]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of Pexidartinib caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[8]
Ripretinib	DM958QB	Moderate	Increased metabolism of Pexidartinib caused by Ripretinib mediated induction of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[7]
Avapritinib	DMK2GZX	Major	Increased metabolism of Pexidartinib caused by Avapritinib mediated induction of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[10]
177Lu-DOTATATE	DMT8GVU	Major	Increased risk of hepatotoxicity by the combination of Pexidartinib and 177Lu-DOTATATE.	Hepatitis virus infection [1E50-1E51]	[8]
Givosiran	DM5PFIJ	Major	Increased risk of hepatotoxicity by the combination of Pexidartinib and Givosiran.	Inborn porphyrin/heme metabolism error [5C58]	[8]
Pemigatinib	DM819JF	Major	Increased metabolism of Pexidartinib caused by Pemigatinib mediated induction of CYP450 enzyme.	Liver cancer [2C12]	[11]
Pralsetinib	DMWU0I2	Major	Increased risk of hepatotoxicity by the combination of Pexidartinib and Pralsetinib.	Lung cancer [2C25]	[8]
Selpercatinib	DMZR15V	Major	Increased metabolism of Pexidartinib caused by Selpercatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[11]
Calaspargase pegol	DMQZBXI	Major	Increased risk of hepatotoxicity by the combination of Pexidartinib and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[8]
Ubrogepant	DM749I3	Moderate	Increased metabolism of Pexidartinib caused by Ubrogepant mediated induction of CYP450 enzyme.	Migraine [8A80]	[12]
Upadacitinib	DM32B5U	Moderate	Increased metabolism of Pexidartinib caused by Upadacitinib mediated induction of CYP450 enzyme.	Rheumatoid arthritis [FA20]	[13]
Voxelotor	DMCS6M5	Major	Decreased metabolism of Pexidartinib caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[8]
Larotrectinib	DM26CQR	Major	Increased risk of hepatotoxicity by the combination of Pexidartinib and Larotrectinib.	Solid tumour/cancer [2A00-2F9Z]	[8]
Fluticasone	DMGCSVF	Moderate	Increased metabolism of Pexidartinib caused by Fluticasone mediated induction of CYP450 enzyme.	Vasomotor/allergic rhinitis [CA08]	[8]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Crospovidone	E00626	Not Available	Disintegrant
Ferric oxide black	E00522	16211978	Colorant
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Poloxamer 407	E00646	Not Available	Emulsifying agent; Solubilizing agent; Surfactant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Colcothar yellow	E00436	518696	Colorant

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Pexidartinib 200 mg capsule	200 mg	Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

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] FDA Approved Drug Products: Turaliotm (pexidartinib) capsules
• [6] 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.
• [7] Cerner Multum, Inc. "Australian Product Information.".
• [8] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [9] Product Information. Mycobutin (rifabutin). Pharmacia and Upjohn, Kalamazoo, MI.
• [10] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [11] Patel S, Robinson R, Burk M "Hypertensive crisis associated with St. John's Wort." Am J Med 112 (2002): 507-8. [PMID: 11959071]
• [12] Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
• [13] Product Information. Rinvoq (upadacitinib). AbbVie US LLC, North Chicago, IL.