PEXIDARTINIB HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H15ClF3N5.ClH
Molecular Weight	454.276
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.FC(F)(F)C1=NC=C(CNC2=NC=C(CC3=CNC4=C3C=C(Cl)C=N4)C=C2)C=C1

InChI

InChIKey=CJLUYLRKLUYCEK-UHFFFAOYSA-N

InChI=1S/C20H15ClF3N5.ClH/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);1H

HIDE SMILES / InChI

Molecular Formula	C20H15ClF3N5
Molecular Weight	417.815
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=659167 | http://www.prnewswire.com/news-releases/fda-grants-breakthrough-therapy-designation-for-daiichi-sankyo-and-plexxikons-investigational-csf-1r-inhibitor-pexidartinib-plx3397-in-tenosynovial-giant-cell-tumor-300169556.html

Pexidartinib (PLX3397) is a small-molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Pexidartinib binds to and inhibits phosphorylation of stem cell factor receptor (KIT), colony-stimulating factor-1 receptor (CSF1R) and FMS-like tyrosine kinase 3 (FLT3), which may result in the inhibition of tumor cell proliferation and down-modulation of macrophages, osteoclasts and mast cells involved in the osteolytic metastatic disease. FDA has granted Breakthrough Therapy Designation to pexidartinib (PLX3397) for the treatment of tenosynovial giant cell tumor (TGCT) where surgical removal of the tumor would be associated with potentially worsening functional limitation or severe morbidity. In addition to Breakthrough Therapy Designation, pexidartinib (PLX3397) has been granted Orphan Drug Designation by FDA for the treatment of pigmented villonodular synovitis (PVNS) and giant cell tumor of the tendon sheath (GCT-TS). It also has received Orphan Designation from the European Commission for the treatment of TGCT.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Stem cell growth factor receptor 53 Target ID: CHEMBL1936 Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=659167	Inhibitor 8297	0.027 µM [IC50]
Macrophage colony stimulating factor receptor 24 Target ID: CHEMBL1844 Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=659167	Inhibitor 8297	0.013 µM [IC50]
Tyrosine-protein kinase receptor FLT3 43 Target ID: CHEMBL1974 Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=659167	Inhibitor 8297	0.16 µM [IC50]
Cell division cycle 2-like protein kinase 6 3 Target ID: CHEMBL6002 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26222558	Inhibitor 8297	0.14 µM [IC50]
Vascular endothelial growth factor receptor 2 104 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26222558	Inhibitor 8297	0.44 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Tenosynovial giant cell tumor 2 Sources: http://www.prnewswire.com/news-releases/fda-grants-breakthrough-therapy-designation-for-daiichi-sankyo-and-plexxikons-investigational-csf-1r-inhibitor-pexidartinib-plx3397-in-tenosynovial-giant-cell-tumor-300169556.html	Primary	Phase III 656	PEXIDARTINIB Approved Use Unknown
Pigmented villonodular synovitis 2 Sources: http://www.prnewswire.com/news-releases/fda-grants-breakthrough-therapy-designation-for-daiichi-sankyo-and-plexxikons-investigational-csf-1r-inhibitor-pexidartinib-plx3397-in-tenosynovial-giant-cell-tumor-300169556.html	Primary	Phase III 656	PEXIDARTINIB Approved Use Unknown
Giant cell tumors of the tendon sheath 2 Sources: http://www.prnewswire.com/news-releases/fda-grants-breakthrough-therapy-designation-for-daiichi-sankyo-and-plexxikons-investigational-csf-1r-inhibitor-pexidartinib-plx3397-in-tenosynovial-giant-cell-tumor-300169556.html	Primary	Phase III 656	PEXIDARTINIB Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
8625 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211810s000lbl.pdf	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		PEXIDARTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
77465 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211810s000lbl.pdf	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		PEXIDARTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
26.6 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211810s000lbl.pdf	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		PEXIDARTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211810s000lbl.pdf	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		PEXIDARTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 mg 2 times / day steady, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211810s000lbl.pdf	unhealthy, 44 years (range: 18-79 years) n = 61 Health Status: unhealthy Condition: symptomatic tenosynovial giant cell tumor Age Group: 44 years (range: 18-79 years) Sex: M+F Population Size: 61 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211810s000lbl.pdf	Disc. AE: ALT increased, AST increased... AEs leading to discontinuation/dose reduction: ALT increased (all grades, 4.9%) AST increased (all grades, 4.9%) Hepatotoxicity (all grades, 3.3%) ALT increased (all grades, 13%) AST increased (all grades, 13%) Nausea (all grades, 8%) ALP increased (all grades, 7%) Vomiting (all grades, 4.9%) Bilirubin increased (all grades, 3.3%) GGT increased (all grades, 3.3%) Dizziness (3.3%) Abdominal pain (3.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211810s000lbl.pdf
400 mg 2 times / day steady, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf Page: p. 149	unhealthy, 44 years (range: 18-79 years) n = 61 Health Status: unhealthy Condition: symptomatic tenosynovial giant cell tumor Age Group: 44 years (range: 18-79 years) Sex: M+F Population Size: 61 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf Page: p. 149	Disc. AE: Hypertension, LDH increased... AEs leading to discontinuation/dose reduction: Hypertension (all grades, 1.6%) LDH increased (all grades, 1.6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf Page: p. 149
5000 mg 1 times / day multiple, oral Studied dose Dose: 5000 mg, 1 times / day Route: oral Route: multiple Dose: 5000 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32330242	unhealthy, 60.6 years (range: 24-82 years) n = 4 Health Status: unhealthy Age Group: 60.6 years (range: 24-82 years) Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/32330242	Sources: https://pubmed.ncbi.nlm.nih.gov/32330242
1000 mg 1 times / day steady, oral MTD Dose: 1000 mg, 1 times / day Route: oral Route: steady Dose: 1000 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30825104	unhealthy, 63 years (range: 40–82 years) n = 8 Health Status: unhealthy Age Group: 63 years (range: 40–82 years) Sex: M+F Population Size: 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30825104	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/30825104
400 mg 2 times / day steady, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211810s000lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211810s000lbl.pdf	Other AEs: Hepatotoxicity... Other AEs: Hepatotoxicity (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211810s000lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587 inducer 781	inhibitor 1767		inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2B6 810 CYP2C8 911 CYP2C19 1478 UGT1A1 204 UGT1A4 77 UGT2B7 146 P-gp 1461 MATE1 306 MATE2 263 OATP1B1 788 OATP1B3 706 OATP2B1 123 BCRP 699 OCT1 512 OCT2 647 BSEP 402	BSEP 52 UGT1A4 347 P-gp 1537 OAT1 326 OAT3 339 OCT1 327 OCT2 355 OATP1B1 406 OATP1B3 350 OATP2B1 104 BCRP 561	CYP2B6 547

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	no
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	no
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	weak
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	yes [IC50 16.7 uM]
UGT1A4 80	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	yes [IC50 22 uM]
UGT2B7 157	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	yes [IC50 26 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	yes [IC50 3.7 uM]
UGT1A1 254	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	yes [IC50 6.9 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	yes [IC50 7.9 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	yes [IC50 9.3 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=101 Page: 67, 87-88	yes [IC50 9.3 uM]	unlikely (co-administration study) Comment: Estimated IC50; Coadministration of pexidartinib decreased the geometric mean Cmax and AUC0-inf of omeprazole (a CYP2C19 substrate) by 37% and 17%, respectively. Comparable decreases in geometric mean Cmax (decrease by 36%) and AUC0-inf (decrease by 23%) were observed for 5-hydroxy omeprazole resulting in similar M/P ratio (73% (OME alone) vs. 72% (OME + Pexidartinib)). The observed similar M/P ratio indicates that pexidartinib had no impact on the CYP2C19 pathway. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=101 Page: 67, 87-88
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	yes
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	yes
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	yes
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	yes
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	yes
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	yes
OATP2B1 126	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	yes
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=101 Page: 67, 87-88	yes	likely (co-administration study) Comment: Coadministration of pexidartinib increased the geometric mean Cmax of digoxin (a P-gp substrate) by 32% with no effect on its AUC0-inf (only 9% increase). The increase in digoxin Cmax is consistent with P-gp inhibitory effect of pexidartinib in the gut. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=101 Page: 67, 87-88

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=101 Page: 58, 62, 67, 68, 83-85	major		yes (co-administration study) Comment: 76 % metabolized by CYP3A4; Itraconazole, a strong CYP3A4 inhibitor (200 mg loading dose then 200 mg once daily for 15 days) increased the geometric mean AUC0-inf and Cmax of pexidartinib by 73% and 48%. Rifampin, a strong CYP3A4 inducer (600 mg once daily for 10 days) reduced the geometric mean AUC0-inf and Cmax of pexidartinib by 63% and 33%, respectively, compared to pexidartinib alone (600 mg single dose). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=101 Page: 58, 62, 67, 68, 83-85
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	no
BSEP 52	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	no
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	no
OATP2B1 104	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	no
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=81 Page: 67.0	no
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=97 Page: 83-85	yes	ZAAD-1006a 2	yes (co-administration study) Comment: Coadministration of itraconazole (strong CYP3A4 inhibitor) increased the geometric mean Cmax and AUC0-inf of ZAAD-1006a by 50% and 97%, respectively. Coadministration of rifampin (strong CYP3A4 inducer) decreased the geometric mean AUC0-inf of ZAAD-1006a by 45%, but increased its Cmax by 35% compared to pexidartinib alone. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=97 Page: 83-85
UGT1A4 347	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=99 Page: 58, 62, 67, 68, 85-86	yes		yes (co-administration study) Comment: 25 % metabolized by UGT1A4; Probenecid, a known UGT inhibitor (500 mg four times a day) increased the geometric mean AUC0-inf of pexidartinib by 60% compared to pexidartinib alone (600 mg single dose) with no effect noted on its Cmax (only 5 % increase). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=99 Page: 58, 62, 67, 68, 85-86
UGT1A4 347	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=99 Page: 85-86	yes	ZAAD-1006a 2	yes (co-administration study) Comment: Coadministration of probenecid (UGT inhibitor) increased the geometric mean AUC0-inf of ZAAD-1006a by 125% with no effect on Cmax (1% decrease) compared to pexidartinib alone. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=99 Page: 85-86

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211810Orig1s000MultidisciplineR.pdf#page=39 Page: 25, 32, 39, 78

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:145373	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:145373
ChemicalBook	CB22742977	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB22742977
MolPort	MolPort-039-193-825	https://www.molport.com/shop/molecule-link/MolPort-039-193-825
ZINC	ZINC000115705166	http://zinc15.docking.org/substances/ZINC000115705166

PubMed

Title	Date	PubMed
Translocation and expression of CSF1 in pigmented villonodular synovitis, tenosynovial giant cell tumor, rheumatoid arthritis and other reactive synovitides.	2007 Jun	17527089
Molecular pathways involved in synovial cell inflammation and tumoral proliferation in diffuse pigmented villonodular synovitis.	2010 Sep	20620241
Synovial colony-stimulating factor-1 mRNA expression in diffuse pigmented villonodular synovitis.	2011 May-Jun	21640049
Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor.	2015 Jul 30	26222558
Colony-Stimulating Factor 1 Receptor Blockade Inhibits Tumor Growth by Altering the Polarization of Tumor-Associated Macrophages in Hepatocellular Carcinoma.	2017 Aug	28572167

Patents

Sample Use Guides

In Vivo Use Guide

1000 mg per day for 2 weeks (dose split over morning and evening), then 800 mg per day for 22 weeks (dose split over morning and evening).

Route of Administration: Oral

In Vitro Use Guide

In vitro, a population doubling assay showed that the IC50 of pexidartinib (PLX3397) for CSF1-induced bone marrow–derived macrophages (M(CSF1)) was 22 nM. Marked suppression of CSF-1R phosphorylation in M(CSF1) cells could be achieved with PLX3397. In contrast, the same doses of PLX3397 showed no antiproliferation effect on Hepa1-6, MHCC97-H, HCCLM3, HepG2, HUVEC, T cells, fibroblasts cells, and CSF2-induced bone marrow–derived macrophages.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:16:53 GMT 2023` Edited by `admin` on `Fri Dec 15 16:16:53 GMT 2023`
Record UNII	YS6WAI3XN7
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PEXIDARTINIB HYDROCHLORIDE

Common Name

English

PEXIDARTINIB HYDROCHLORIDE [JAN]

Common Name

English

PLX3397 HYDROCHLORIDE

Code

English

PEXIDARTINIB HYDROCHLORIDE [USAN]

Common Name

English

Pexidartinib hydrochloride [WHO-DD]

Common Name

English

PLX-3397 HCL

Code

English

PLX-3397 HYDROCHLORIDE

Code

English

5-((5-CHLORO-1H-PYRROLO(2,3-B)PYRIDIN-3-YL)METHYL)-N-((6-(TRIFLUOROMETHYL)PYRIDIN-3-YL)METHYL)PYRIDIN-2-AMINE HYDROCHLORIDE

Systematic Name

English

PLX3397 HCL

Code

English

PEXIDARTINIB HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

(5-(5-CHLORO-1H-PYRROLO(2,3-B)PYRIDIN-3-YLMETHYL)-PYRIDIN-2-YL)-(6-TRIFLUOROMETHYL-PYRIDIN-3-YLMETHYL)-AMINE HYDROCHLORIDE SALT

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

419913