Pexidartinib (PLX3397)
Pexidartinib (PLX3397; CAS 1029044-16-3) is a small molecule inhibitor targeting colony-stimulating factor 1 receptor (CSF-1R), a receptor tyrosine kinase involved in macrophage recruitment and activation. Through inhibition of CSF-1R activity, this compound reduces macrophage infiltration and accumulation, demonstrated by diminished macrophage levels in B16F10 melanoma models, without affecting Gr-1+ myeloid-derived suppressor cells. In vivo studies using GL261 glioma models in C57 mice indicate decreased microglial infiltration upon oral dosing with PLX3397. Clinically, combined treatment with Pexidartinib and paclitaxel is under evaluation in advanced solid tumors and breast cancer trials.
Reference:
[1] Sluijter M, van der Sluis TC, van der Velden PA, Versluis M, West BL, van der Burg SH, van Hall T. Inhibition of CSF-1R supports T-cell mediated melanoma therapy. PLoS One. 2014 Aug 11;9(8):e104230.
[2] Coniglio SJ, Eugenin E, Dobrenis K, Stanley ER, West BL, Symons MH, Segall JE. Microglial stimulation of glioblastoma invasion involves epidermal growth factor receptor (EGFR) and colony stimulating factor 1 receptor (CSF-1R) signaling. Mol Med. 2012 May 9;18:519-27.
- 1. Jinchao Gao, Qingxiang Song, et al. "Intracerebral fate of organic and inorganic nanoparticles is dependent on microglial extracellular vesicle function." Nat Nanotechnol. 2024 Mar;19(3):376-386. PMID: 38158436
- 2. Sanghoon Lee, Rebekah Karns, et al. "Mechanism of paracrine communications between hepatic progenitor cells and endothelial cells." Cell Signal. 2022 Aug 30;100:110458. PMID: 36055565
- 3. Nina M. Dräger, Sydney M. Sattler, et al. "A CRISPRi/a platform in human iPSC-derived microglia uncovers regulators of disease states." Nat Neurosci. 2022 Sep;25(9):1149-1162. PMID: 35953545
- 4. Komohara Y, Noyori O, et al. "Potential anti-lymphoma effect of M-CSFR inhibitor in adult T-cell leukemia/lymphoma." J Clin Exp Hematop. 2018;58(4):152-160. PMID: 30541986
- 5. Yu R, Jin H, et al. "Inhibition of the CSF-1 receptor sensitizes ovarian cancer cells to cisplatin." Cell Biochem Funct. 2018 Jan 25. PMID: 29372560
- 6. Wang C, Yeo S, et al. "Autophagy gene FIP200 in neural progenitors non-cell autonomously controls differentiation by regulating microglia." J Cell Biol. 2017 Jun 20. pii: jcb.201609093. PMID: 28634261
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 417.81 |
| Cas No. | 1029044-16-3 |
| Formula | C20H15ClF3N5 |
| Solubility | insoluble in EtOH; insoluble in H2O; ≥20.9 mg/mL in DMSO |
| Chemical Name | 5-((5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)pyridin-2-amine |
| SDF | Download SDF |
| Canonical SMILES | ClC(C=N1)=CC2=C1NC=C2CC3=CN=C(NCC4=CN=C(C(F)(F)F)C=C4)C=C3 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
|
Cell lines |
SK-N-SH cells |
|
Preparation method |
The solubility of this compound in DMSO is >20.9mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
IC50: 10 μM |
|
Applications |
Pexidartinib weakly inhibited the growth of SK-N-SH cells with an IC50 of 10 μM. PLX3397 had little or no effect on the growth of MDA-MB-231 human tumor cells grown as xenografts. |
| Animal experiment [1,2]: | |
|
Animal models |
C57BL/6 mice xenografted with B16F10 melanoma cells, Female nude mice bearing MDA-MB-468 human breast tumor cells xenografts |
|
Dosage form |
Oral administration, daily doses of approximately 45 mg/kg |
|
Application |
Pexidartinib predominantly affected F4/80+ Ly6C- blood macrophages and strongly decreased the CSF-1R expression levels on F4/80+ Ly6C+ ‘inflammatory’ monocytes. Oral dosing of PLX3397 prevented the rise in osteoclasts and the loss of bone. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1] West B L, DeNardo D G, Tsai J, et al. Efficacy of the selective CSF-1R kinase inhibitor PLX3397 in mouse models of tumor growth and bone metastasis[J]. 2010. [2] Sluijter M, van der Sluis T C, van der Velden P A, et al. Inhibition of CSF-1R supports T-cell mediated melanoma therapy[J]. PloS one, 2014, 9(8): e104230. |
|
Quality Control & MSDS
- View current batch:
Chemical structure
Related Biological Data
Related Biological Data
Related Biological Data
Related Biological Data
Related Biological Data
