Identification

Name
Pexidartinib
Accession Number
DB12978
Type
Small Molecule
Groups
Approved, Investigational
Description

Pexidartinib is a selective tyrosine kinase inhibitor that works by inhibiting the colony-stimulating factor (CSF1)/CSF1 receptor pathway. Pexidartinib was originally developed by Daiichi Sankyo, Inc. and it was approved by the FDA in August 2019 as the first systemic therapy for adult patients with symptomatic tenosynovial giant cell tumor.11 Tenosynovial giant cell tumor is a rare form of non-malignant tumor that causes the synovium and tendon sheaths to thicken and overgrow, leading to damage in surrounding joint tissue.1,11 Debilitating symptoms often follow with tenosynovial giant cell tumors, along with a risk of significant functional limitations and a reduced quality of life in patients.11

While surgical resection is a current standard of care for tenosynovial giant cell tumor, there are tumor types where surgeries are deemed clinically ineffective with a high risk of lifetime recurrence.10 Pexidartinib works by blocking the immune responses that are activated in tenosynovial giant cell tumors. In clinical trials, pexidartinib was shown to promote improvements in patient symptoms and functional outcomes in TGCT.2 Pexidartinib is available in oral formulations and it is commonly marketed as Turalio.11

Structure
Thumb
Synonyms
  • Pexidartinib
External IDs
CML-261 / PLX-3397 / PLX3397
Product Ingredients
IngredientUNIICASInChI Key
Pexidartinib hydrochlorideYS6WAI3XN72040295-03-0CJLUYLRKLUYCEK-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TuralioCapsule200 mg/1OralDaiichi Sankyo Inc.2019-08-02Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories
UNII
6783M2LV5X
CAS number
1029044-16-3
Weight
Average: 417.82
Monoisotopic: 417.0968077
Chemical Formula
C20H15ClF3N5
InChI Key
JGWRKYUXBBNENE-UHFFFAOYSA-N
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)
IUPAC Name
5-({5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl}methyl)-N-{[6-(trifluoromethyl)pyridin-3-yl]methyl}pyridin-2-amine
SMILES
FC(F)(F)C1=CC=C(CNC2=NC=C(CC3=CNC4=NC=C(Cl)C=C34)C=C2)C=N1

Pharmacology

Indication

Pexidartinib is indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery.9

Associated Conditions
Pharmacodynamics

Pexidartinib works by suppressing the growth of tenosynovial giant cell tumors. In clinical trials comprising of patients with symptomatic tenosynovial giant cell tumor, pexidartinib had a higher overall response rate, characterized by improved patient symptoms and functional outcomes, compared to placebo.2 Pexidartinib works by inhibiting the activation and signaling of tumor-permissive cytokines and receptor tyrosine kinases that play a central role in tumor cell proliferation and survival.3

Mechanism of action

Tenosynovial giant cell tumor is a rare, non-malignant neoplasm that causes abnormal growth and damage to the synovium, bursae, or tendon sheaths.11 Recruitment of immune cells, specifically macrophages, is closely associated with the tumor mass formation in tenosynovial giant cell tumors. 1 Macrophages drive tumor-promoting inflammation 7 and play a central role in every stage of tumor progression.6 As the most abundant immune cells in the tumor microenvironment of solid tumors, macrophages promote processes that enhance tumor survival, such as angiogenesis, tumor cell invasion, and intravasation at the primary site.6 They also modulate the immune response to tumors to inhibit tumor clearance and directly engage with tumor cells to activate pro-survival signaling pathways.8

The recruitment, proliferation, and irreversible differentiation of macrophages are regulated by colony-stimulating factor-1 (CSF-1),3,5 which is a cytokine that is often translocated and highly expressed in tenosynovial giant cell tumors.8 Elevated expression of CSF-1 and CSF-1 receptor (CSF1R) has also been implicated in various models of malignant cancers and tumors.4 Pexidartinib targets the CSF1/CSF1R pathway as a selective CSF1R inhibitor. It stimulates the autoinhibited state of the CSF1R by interacting with the juxtamembrane region of CSF1R, which is responsible for folding and inactivation of the kinase domain, and preventing the binding of CSF1 and ATP to the region.1 Without the binding of CSF1 to the receptor, CSF1R cannot undergo ligand-induced autophosphorylation.9 By inhibiting the CSF1R signaling pathway, pexidartinib works to inhibit tumor cell proliferation and downmodulate cells involved in the disease, such as macrophages. It was also shown to inhibit the CD117 or proto-oncogene receptor tyrosine kinase (cKIT), mutant fms-like tyrosine kinase 3 (FLT3), and platelet-derived growth factor receptor (PDGFR)-β, which are all receptor tyrosine kinases that regulate critical cellular processes such as cell proliferation and survival.3

TargetActionsOrganism
AMacrophage colony-stimulating factor 1 receptor
inhibitor
Humans
UMast/stem cell growth factor receptor Kit
inhibitor
Humans
UReceptor-type tyrosine-protein kinase FLT3
inhibitor
Humans
UPlatelet-derived growth factor receptor beta
inhibitor
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Following administration of single doses in healthy subjects and multiple doses in patients, the mean Cmax was 8625 ng/mL and the mean AUC was 77465 ngxh/mL. The median Tmax was 2.5 hours and the time to reach the steady state was approximately 7 days. Administration of pexidartinib with a high fat meal resulted in an increased drug Cmax and AUC by 100%, with a delay in Tmax by 2.5 hours.9

Volume of distribution

The apparent volume of distribution of pexidartinib is about 187 L.9 In rats, pexidartinib was shown to penetrate into the central nervous system.10

Protein binding

Based on the findings of in vitro plasma protein binding study, pexidartinib is about 99% bound to serum proteins, where it is extensively bound to human serum albumin by 99.9% and alpha-1-acid glycoprotein by 89.9%.9

Metabolism

Pexidartinib primarily undergoes oxidation mediated by hepatic CYP3A4 and glucuronidation by UGT1A4. Following UGT1A4-mediated glucuronidation, a major inactive N-glucuronide metabolite is formed with approximately 10% higher exposure than the parent drug after a single dose administration of pexidartinib.9 Based on the findings of in vitro studies, CYP1A2 and CYP2C9 may also play a minor role in drug metabolism.10

Route of elimination

Pexidartinib is predominantly excreted via feces, where fecal excretion accounts for 65% of total pexidartinib elimination. Via this route of elimination, about 44% of the compound found in feces is recovered as unchanged parent drug. The renal elimination accounts for 27% of pexidartinib elimination, where more than 10% of the compound is found as the N-glucuronide metabolite.9

Half life

The elimination half-life is about 26.6 hours.9

Clearance

The apparent clearance is about 5.1 L/h.9

Toxicity

There is limited human data on the overdose of pexidartinib. In 4-week toxicology studies, the no-observed-adverse-effect levels (NOAELs) of pexidatrtinib were determined to be 10 mg/kg/day in rats and 6 mg/kg/day in dogs.10 Pexidartinib was shown to cause hepatotoxicity in clinical trials, including mixed or cholestatic hepatotoxicity,2 and embryo-fetal toxicity in animal studies.9

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
3,5-diiodothyropropionic acidThe therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Pexidartinib.
3,5-DiiodotyrosineThe therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Pexidartinib.
6-Deoxyerythronolide BThe metabolism of Pexidartinib can be decreased when combined with 6-Deoxyerythronolide B.
7-ethyl-10-hydroxycamptothecinThe metabolism of Pexidartinib can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
9-aminocamptothecinThe metabolism of Pexidartinib can be decreased when combined with 9-aminocamptothecin.
AbacavirThe metabolism of Abacavir can be decreased when combined with Pexidartinib.
AbaloparatideThe therapeutic efficacy of Abaloparatide can be decreased when used in combination with Pexidartinib.
AbataceptThe metabolism of Pexidartinib can be increased when combined with Abatacept.
AbemaciclibThe excretion of Abemaciclib can be decreased when combined with Pexidartinib.
AcalabrutinibThe metabolism of Pexidartinib can be decreased when combined with Acalabrutinib.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of pexidartinib.
  • Avoid St. John's Wort. This herb induces the CYP3A metabolism of pexidartinib and may reduce its serum concentration.
  • Take on an empty stomach. Take at least 1 hour before or 2 hours after eating a meal or snack.
  • Take separate from antacids. Take antacids at least 2 hours before or after pexidartinib.

References

Synthesis Reference

Chen D, Zhang Y, Li J, Liu Y: Exploratory Process Development of Pexidartinib through the Tandem Tsuji–Trost Reaction and Heck Coupling. Synthesis. 2019 January 4;51(12):2564-2571. doi:10.1055/s-0037-1612421.

General References
  1. Giustini N, Bernthal NM, Bukata SV, Singh AS: Tenosynovial giant cell tumor: case report of a patient effectively treated with pexidartinib (PLX3397) and review of the literature. Clin Sarcoma Res. 2018 Jul 10;8:14. doi: 10.1186/s13569-018-0101-2. eCollection 2018. [PubMed:30002809]
  2. Tap WD, Gelderblom H, Palmerini E, Desai J, Bauer S, Blay JY, Alcindor T, Ganjoo K, Martin-Broto J, Ryan CW, Thomas DM, Peterfy C, Healey JH, van de Sande M, Gelhorn HL, Shuster DE, Wang Q, Yver A, Hsu HH, Lin PS, Tong-Starksen S, Stacchiotti S, Wagner AJ: Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial. Lancet. 2019 Jun 19. pii: S0140-6736(19)30764-0. doi: 10.1016/S0140-6736(19)30764-0. [PubMed:31229240]
  3. Cannarile MA, Weisser M, Jacob W, Jegg AM, Ries CH, Ruttinger D: Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017 Jul 18;5(1):53. doi: 10.1186/s40425-017-0257-y. [PubMed:28716061]
  4. Espinosa I, Beck AH, Lee CH, Zhu S, Montgomery KD, Marinelli RJ, Ganjoo KN, Nielsen TO, Gilks CB, West RB, van de Rijn M: Coordinate expression of colony-stimulating factor-1 and colony-stimulating factor-1-related proteins is associated with poor prognosis in gynecological and nongynecological leiomyosarcoma. Am J Pathol. 2009 Jun;174(6):2347-56. doi: 10.2353/ajpath.2009.081037. Epub 2009 May 14. [PubMed:19443701]
  5. Hume DA, MacDonald KP: Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling. Blood. 2012 Feb 23;119(8):1810-20. doi: 10.1182/blood-2011-09-379214. Epub 2011 Dec 20. [PubMed:22186992]
  6. Nielsen SR, Schmid MC: Macrophages as Key Drivers of Cancer Progression and Metastasis. Mediators Inflamm. 2017;2017:9624760. doi: 10.1155/2017/9624760. Epub 2017 Jan 22. [PubMed:28210073]
  7. Mantovani A, Marchesi F, Malesci A, Laghi L, Allavena P: Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol. 2017 Jul;14(7):399-416. doi: 10.1038/nrclinonc.2016.217. Epub 2017 Jan 24. [PubMed:28117416]
  8. Cupp JS, Miller MA, Montgomery KD, Nielsen TO, O'Connell JX, Huntsman D, van de Rijn M, Gilks CB, West RB: Translocation and expression of CSF1 in pigmented villonodular synovitis, tenosynovial giant cell tumor, rheumatoid arthritis and other reactive synovitides. Am J Surg Pathol. 2007 Jun;31(6):970-6. doi: 10.1097/PAS.0b013e31802b86f8. [PubMed:17527089]
  9. FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
  10. TURALIO (PEXIDARTINIB) CAPSULES - Daiichi Sankyo, Inc. - FDA Oncologic Drugs Advisory Committee Briefing Document [Link]
  11. FDA approves first therapy for rare joint tumor - FDA News Release [Link]
External Links
PubChem Compound
25151352
PubChem Substance
347829117
ChemSpider
35308322
BindingDB
50177716
RxNav
2183102
ChEBI
145373
ChEMBL
CHEMBL3813873
ZINC
ZINC000115705166
PDBe Ligand
P31
Wikipedia
Pexidartinib
PDB Entries
4r7h

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentModerate Hepatic Impairment1
1Active Not RecruitingTreatmentAdvanced Solid Tumors1
1Active Not RecruitingTreatmentDrug Interaction Potential1
1Active Not RecruitingTreatmentGastrointestinal Stromal Tumors (GISTs)1
1Active Not RecruitingTreatmentTumors, Solid1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic SciencePharmacokinetics in Healthy Volunteers1
1CompletedTreatmentCancer, Advanced / Colorectal Cancers / Malignant Neoplasm of Pancreas / Metastatic Cancers1
1CompletedTreatmentTumors, Solid1
1SuspendedTreatmentStage I Prostate Adenocarcinoma / Stage II Prostate Adenocarcinoma / Stage III Prostate Adenocarcinoma1
1TerminatedTreatmentStage III or Stage IV Metastatic Melanoma That Has Not Been Previously Treated With a Selective BRAF Inhibitor / V600-mutated BRAF Metastatic Melanoma / V600-mutated BRAF Unresectable Melanoma1
1WithdrawnTreatmentRheumatoid Arthritis1
1, 2Active Not RecruitingTreatmentGastrointestinal Stromal Tumors1
1, 2Active Not RecruitingTreatmentPatients With Newly Diagnosed Glioblastoma1
1, 2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2CompletedTreatmentMetastatic Breast Cancer1
1, 2RecruitingTreatmentLeukemia, Prolymphocytic, Acute / Plexiform Neurofibroma / Precursor Cell Lymphoblastic Leukemia-Lymphoma / Sarcomas1
1, 2RecruitingTreatmentMalignant Peripheral Nerve Sheath Tumour (MPNST) / Sarcomas1
1, 2TerminatedTreatmentCancer, Bladder / Gastrointestinal Stromal Tumors (GISTs) / GIST / Lung Cancer Non-Small Cell Cancer (NSCLC) / Malignant Neoplasm of Stomach / Melanoma / Ovarian Cancer / Pancreatic Ductal Adenocarcinoma / Squamous Cell Carcinoma of the Head and Neck (SCCHN) / Triple Negative Breast Cancer (TNBC) / Triple-Negative Breast Cancer (TNBC)1
2CompletedTreatmentLymphoma, Hodgkins1
2RecruitingTreatmentBreast Cancer / Hemangiosarcoma / Neoplasms, Breast / Tumors, Breast1
2RecruitingTreatmentMelanoma, Malignant1
2TerminatedTreatmentProstate Cancer1
2TerminatedTreatmentRecurrent Glioblastoma1
3Active Not RecruitingTreatmentGiant Cell Tumors of the Tendon Sheath / Synovitis, Pigmented Villonodular / Tenosynovial Giant Cell Tumor / Tenosynovial Giant Cell Tumour1
Not AvailableActive Not RecruitingTreatmentMelanoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral200 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9358235No2016-06-072033-06-08Us
US8461169No2013-06-112028-04-19Us
US10189833No2019-01-292036-05-05Us
US9169250No2015-10-272027-11-21Us
US10435404No2019-10-082038-07-24Us
US8404700No2013-03-262027-11-21Us
US8722702No2014-05-132027-11-21Us
US7893075No2011-02-222028-10-13Us
US9802932No2017-10-312036-05-05Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00315 mg/mLALOGPS
logP4.64ALOGPS
logP4.54ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)15.68ChemAxon
pKa (Strongest Basic)6.76ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area66.49 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity105.89 m3·mol-1ChemAxon
Polarizability39.33 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as pyrrolopyridines. These are compounds containing a pyrrolopyridine moiety, which consists of a pyrrole ring fused to a pyridine. Pyrrole is 5-membered ring consisting of four carbon atoms and one nitrogen atom. Pyridine is a 6-membered ring consisting of five carbon atoms and one nitrogen center.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyrrolopyridines
Sub Class
Not Available
Direct Parent
Pyrrolopyridines
Alternative Parents
Aminopyridines and derivatives / Substituted pyrroles / Imidolactams / Aryl chlorides / Heteroaromatic compounds / Azacyclic compounds / Organofluorides / Organochlorides / Hydrocarbon derivatives / Amines
show 1 more
Substituents
Pyrrolopyridine / Aminopyridine / Aryl chloride / Aryl halide / Pyridine / Substituted pyrrole / Imidolactam / Pyrrole / Heteroaromatic compound / Azacycle
show 10 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein homodimerization activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor ...
Gene Name
CSF1R
Uniprot ID
P07333
Uniprot Name
Macrophage colony-stimulating factor 1 receptor
Molecular Weight
107982.955 Da
References
  1. Cannarile MA, Weisser M, Jacob W, Jegg AM, Ries CH, Ruttinger D: Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017 Jul 18;5(1):53. doi: 10.1186/s40425-017-0257-y. [PubMed:28716061]
  2. FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
  3. TURALIO (PEXIDARTINIB) CAPSULES - Daiichi Sankyo, Inc. - FDA Oncologic Drugs Advisory Committee Briefing Document [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell main...
Gene Name
KIT
Uniprot ID
P10721
Uniprot Name
Mast/stem cell growth factor receptor Kit
Molecular Weight
109863.655 Da
References
  1. Cannarile MA, Weisser M, Jacob W, Jegg AM, Ries CH, Ruttinger D: Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017 Jul 18;5(1):53. doi: 10.1186/s40425-017-0257-y. [PubMed:28716061]
  2. TURALIO (PEXIDARTINIB) CAPSULES - Daiichi Sankyo, Inc. - FDA Oncologic Drugs Advisory Committee Briefing Document [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells...
Gene Name
FLT3
Uniprot ID
P36888
Uniprot Name
Receptor-type tyrosine-protein kinase FLT3
Molecular Weight
112902.51 Da
References
  1. Cannarile MA, Weisser M, Jacob W, Jegg AM, Ries CH, Ruttinger D: Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017 Jul 18;5(1):53. doi: 10.1186/s40425-017-0257-y. [PubMed:28716061]
  2. TURALIO (PEXIDARTINIB) CAPSULES - Daiichi Sankyo, Inc. - FDA Oncologic Drugs Advisory Committee Briefing Document [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vascular endothelial growth factor binding
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...
Gene Name
PDGFRB
Uniprot ID
P09619
Uniprot Name
Platelet-derived growth factor receptor beta
Molecular Weight
123966.895 Da
References
  1. Cannarile MA, Weisser M, Jacob W, Jegg AM, Ries CH, Ruttinger D: Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017 Jul 18;5(1):53. doi: 10.1186/s40425-017-0257-y. [PubMed:28716061]
  2. TURALIO (PEXIDARTINIB) CAPSULES - Daiichi Sankyo, Inc. - FDA Oncologic Drugs Advisory Committee Briefing Document [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A4
Uniprot ID
P22310
Uniprot Name
UDP-glucuronosyltransferase 1-4
Molecular Weight
60024.535 Da
References
  1. FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Drug transmembrane transporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
References
  1. FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]

Drug created on October 20, 2016 19:45 / Updated on May 16, 2020 15:52

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