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PLX3397 (Pexidartinib)

CAS No.
1029044-16-3
Chemical Name:
PLX3397 (Pexidartinib)
Synonyms
Pexidartinib;Turalio;PLX-3397;Pexidartinib (PLX3397);[5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(6-trifluoromethyl-pyridin-3-ylmethyl)-amine;PLX339;CML261;FP113);CS-1695;Peridartinib
CBNumber:
CB22742977
Molecular Formula:
C20H15ClF3N5
Molecular Weight:
417.81
MDL Number:
MFCD28900745
MOL File:
1029044-16-3.mol
MSDS File:
SDS
Last updated:2024-01-22 16:23:20

PLX3397 (Pexidartinib) Properties

Density 1.458±0.06 g/cm3(Predicted)
storage temp. -20°C
solubility Soluble in DMSO (up to at least 10 mg/ml)
pka 12.81±0.40(Predicted)
form solid
color White
Stability Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months.
CAS DataBase Reference 1029044-16-3
FDA UNII 6783M2LV5X
ATC code L01EX15

SAFETY

Risk and Safety Statements

Symbol(GHS)  GHS hazard pictograms
GHS07
Signal word  Warning
Hazard statements  H302-H315-H319-H335
Precautionary statements  P261-P305+P351+P338

PLX3397 (Pexidartinib) price More Price(29)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Cayman Chemical 18271 Pexidartinib ≥98% 1029044-16-3 5mg $62 2024-03-01 Buy
Cayman Chemical 18271 Pexidartinib ≥98% 1029044-16-3 10mg $115 2024-03-01 Buy
Cayman Chemical 18271 Pexidartinib ≥98% 1029044-16-3 25mg $270 2024-03-01 Buy
Cayman Chemical 18271 Pexidartinib ≥98% 1029044-16-3 50mg $419 2024-03-01 Buy
TRC P293625 Pexidartinib 1029044-16-3 100mg $305 2021-12-16 Buy
Product number Packaging Price Buy
18271 5mg $62 Buy
18271 10mg $115 Buy
18271 25mg $270 Buy
18271 50mg $419 Buy
P293625 100mg $305 Buy

PLX3397 (Pexidartinib) Chemical Properties,Uses,Production

Application

Pexidartinib is a small-molecule, oral, potent multi-targeted receptor tyrosine kinase (RTK) inhibitor of CSF-1R, Kit, and Flt3 and it can cross the blood-brain barrier. In M-NFS-60, Bac 1.2F5 and M-07e cells, PLX3397 (Pexidartinib) inhibits the CSF1-dependent proliferation with IC50 of 0.44 μM, 0.22 μM and 0.1 μM, respectively. It has been reported that PLX3397 strongly attenuates systemic and local accumulation of macrophages driven by B16F10 melanoma and does not affect Gr-1+ bone marrow-derived suppressor cells. Besides, PLX3397 weakly inhibited the growth of SK-N-SH cells with an IC50 of 10 μM and had little effect on the growth of MDA-MB-231 human tumor cell xenografts. In MMTV-PyMT mice, pexidartinib (40 mg/kg, p.o.) significantly inhibits both steady-state and PTX-induced tumor infiltration by CD45 + CD11b + Ly6C − Ly6G − F4/80 +. Pexidartinib/PTX therapy also results in a significant reduction in CD31+ vessel density within mammary tumors, paralleling induction of apoptosis and necrosis.

Description

Pexidartinib (TURALIO™) is a novel, orally available small molecule tyrosine kinase inhibitor (TKI) with potent and selective activity against the colony-stimulating factor 1 (CSF1) receptor. Pexidartinib also inhibits KIT proto-oncogene receptor tyrosine kinase (KIT) and FMS-like tyrosine kinase 3 harboring an internal tandem duplication mutation (FLT3-ITD). Pexidartinib has been developed by Daiichi Sankyo for the treatment of tenosynovial giant cell tumor (TGCT; also known as giant cell tumor of the tendon sheath or pigmented villonodular synovitis.

Synthetic Routes

The synthetic routes of pexidartinib were developed by Daiichi Sankyo Company6. A novel efficient synthetic route for pexidartinib was designed via Tsuji–Trost/Heck tandem reaction in combination with palladium and silver catalysis, which avoids the need for ultra-low temperature and greatly reduces the amount of corrosive trifluoroacetic acid. The cheap and easily available materials and reagents and easy operations for workup and purification make this route more practical.

Anti-tumor Activity

Administration of PLX3397 reduced CIBP, induced substantial intratumoral fibrosis, and was also highly efficacious in reducing tumor cell growth, formation of new tumor colonies in bone, and pathological tumor-induced bone remodeling. PLX3397 is superior to imatinib in the treatment of malignant peripheral nerve sheath tumor (MPNST), and the combination of PLX3397 with a TORC1 inhibitor could provide a new therapeutic approach for the treatment of this disease.

Description

Colony stimulating factor 1 (CSF1) is a cytokine that is involved in the recruitment and activation of tissue macrophages. It exerts these effects by binding to its corresponding receptor tyrosine kinase, the cFMS/CSF1 receptor (CSF1R). Pexidartinib is a brain-penetrant inhibitor of CSF1R, as well as c-Kit and FLT3 (IC50s = 20, 10, and 160 nM in vitro, respectively). It has been used in combination with paclitaxel to block macrophage recruitment in mammary tumor-bearing mice, thus slowing primary tumor development and metastasis. Pexidartinib has also been used to block microglial stimulation of glioblastoma invasion in both cell culture and a mouse model of glioblastoma multiforme.

Uses

Pexidartinib is RTK inhibitor. It can be used in pharmacological activity, therapeutic use, and biological study of inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition.

Definition

ChEBI: Pexidartinib is a pyrrolopyridine that is 5-chloro-1H-pyrrolo[2,3-b]pyridine which is substituted by a [6-({[6-(trifluoromethyl)pyridin-3-yl]methyl}amino)pyridin-3-yl]methyl group at position 3. It is a potent multi-targeted receptor tyrosine kinase inhibitor of CSF-1R, KIT, and FLT3 (IC50 of 20 nM, 10 nM and 160 nM, respectively). Approved by the FDA for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT). It has a role as an EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor and an antineoplastic agent. It is a pyrrolopyridine, an organochlorine compound, an aminopyridine, an organofluorine compound and a secondary amino compound.

in vitro

plx3397 strongly dampened the systemic and local accumulation of macrophages driven by b16f10 melanomas, without affecting gr-1+ myeloid derived suppressor cells [1].

in vivo

wild-type c57 mice were orthotopically injected with gl261 cells and fed with plx3397 compound. after 2 wks, tumors in the control group showed extensive microglia infiltration. in animals fed plx3397, however, there was a substantial reduction in the number of iba1- positive cells at the tumor [2].

storage

Store at -20°C

References

1)?DeNardo?et al.?(2011)?Leukocyte Complexity Predicts Breast Cancer Survival and Functionally Regulates Response to Chemotherapy;?Cancer Discov.?1?54 2)?Mok?et al.?(2014)?Inhibition of CSF-1 receptor improves the antitumor efficacy of adoptive cell transfer immunotherapy;?Cancer Res.74?15 3)Sluijter?et al.?(2014)?Inhibition of CSF-1R supports T-cell mediated melanoma therapy;?PLoS One?9?e104230 4)?Peranzoni?et al.?(2018)?Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti-PD-1 treatment;?Proc. Natl. Acad. Sci. USA?115?E4041 5)?Shi?et al.?(2019)?Modulating the Tumor Microenvironment via Oncolytic Viruses and CSF-1R Inhibition Synergistically Enhances Anti-PD-1 Immunotherapy;?Mol. Ther.?27?244 6) Dammeijer?et al.?(2017)?Depletion pf Tumor-Associated Macrophages with a CSF-1R Kinase Inhibitor Enhances Antitumor Immunity and Survival Induced by DC Immunotherapy;?Cancer Immunol. Res.?5?535

PLX3397 (Pexidartinib) Preparation Products And Raw materials

Raw materials

Preparation Products

Global( 151)Suppliers
Supplier Tel Email Country ProdList Advantage
Hangzhou FandaChem Co.,Ltd.
008657128800458; +8615858145714 fandachem@gmail.com China 9354 55
ATK CHEMICAL COMPANY LIMITED
+undefined-21-51877795 ivan@atkchemical.com China 32480 60
Biochempartner
0086-13720134139 candy@biochempartner.com CHINA 967 58
BOC Sciences
+1-631-485-4226 inquiry@bocsci.com United States 19553 58
Chengdu Feibo Pharm Technology Co., Ltd
15982321820 abby@arkpharm.com CHINA 3279 58
TopScience Biochemical
00852-68527855 info@itopbiochem.com China Hong Kong 902 58
career henan chemical co
+86-0371-86658258 15093356674; factory@coreychem.com China 29826 58
TargetMol Chemicals Inc.
+1-781-999-5354 +1-00000000000 marketing@targetmol.com United States 19892 58
HANGZHOU CLAP TECHNOLOGY CO.,LTD
86-571-88216897,88216896 13588875226 sales@hzclap.com CHINA 6313 58
Dideu Industries Group Limited
+86-29-89586680 +86-15129568250 1026@dideu.com China 29831 58

Related articles

  • What is PLX3397 (Pexidartinib)?
  • PLX3397 (Pexidartinib) is a small-molecule, oral, potent multi-targeted receptor tyrosine kinase (RTK) inhibitor of CSF-1R, Ki....
  • Feb 24,2020
  • PLX3397 (Pexidartinib)
  • Pexidartinib (TURALIO) is a novel, orally available small molecule tyrosine kinase inhibitor (TKI) with potent and selective a....
  • Dec 11,2019

View Lastest Price from PLX3397 (Pexidartinib) manufacturers

Image Update time Product Price Min. Order Purity Supply Ability Manufacturer
PLX3397 (Pexidartinib) USP/EP/BP pictures 2021-08-18 PLX3397 (Pexidartinib) USP/EP/BP
1029044-16-3
US $1.10 / g 1g 99.9% 100 Tons min Dideu Industries Group Limited
PLX3397 (Pexidartinib) pictures 2021-07-13 PLX3397 (Pexidartinib)
1029044-16-3
US $15.00-10.00 / KG 1KG 99%+ HPLC Monthly supply of 1 ton Zhuozhou Wenxi import and Export Co., Ltd
PLX3397 (Pexidartinib) pictures 2021-07-10 PLX3397 (Pexidartinib)
1029044-16-3
US $15.00-10.00 / KG 1KG 99%+ HPLC Monthly supply of 1 ton Zhuozhou Wenxi import and Export Co., Ltd
5-((5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl) 3-Pyridinemethanamine,N-[5-[(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-2-pyridinyl]-6-(trifluoromethyl)- N-[5-[(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-2-pyridinyl]-6-(trifluoromethyl)-3-pyridinemethanamine PLX3397 (Pexidartinib) PLX339 5-((5-chloro-1H-pyrrolo[2,3-b]pyridin-2-yl)methyl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)pyridin-2-amine 5-[(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-N-[[6-(trifluoromethyl)pyridin-3-yl]methyl]pyridin-2-amine CS-1695 PLX3397;PLX 3397;PLX-3397 PLX3397 (Pexidartinib) USP/EP/BP Peridartinib CML261 FP113) PLX-3397 Pexidartinib (PLX3397) Pexidartinib [5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(6-trifluoromethyl-pyridin-3-ylmethyl)-amine Turalio 13C,2H4]-Peridartinib PLX3397,inhibit,PLX 3397,CSF-1 receptor,SCFR,Pexidartinib,Inhibitor,c-Fms,Apoptosis,CSF-1R,colony stimulating factor 1 receptor,CSF1R,CD117,c-Kit 5-[[5-Chloropyrrolo[2,3-b]pyridin-3-yl]methyl]-2-[[[6-(trifluoromethyl)-3-pyridyl]methyl]amino]pyridine Morinidazole Impurity 14 1029044-16-3 1029004-16-3 C20H15ClF3N5 Inhibitors API