| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 10mg | 电议 |
| 50mg | 电议 |
Cell lines | LM8(RCB1450)、NFSa(RCB0282)、KUM5(RCB2322)、LAG(RCB2758) |
Reaction Conditions | a 10mmol/L stock of pexidartinib was formulated in dimethyl sulfoxide (DMSO) |
Applications | In vitro administration of pexidartinib suppressed pERK1/2 stimulation by CSF1 or TCM. CSF1R blockade in the in vitro TAM model resulted in reduced viability and chemotaxis of macrophages and polarization from M2-like to a more M1-like phenotype |
Animal models | Two-month-old 5XFAD mice |
Preparation Method | Treated two-month-old 5XFAD mice with pexidartinib, for a period of 3 months, resulting in a significant ablation of microglia. Directly after this treatment, analyse the amount of intraneuronal amyloid and neuritic plaques and performed behavioral studies including Y-maze, fear conditioning and elevated plus maze |
Dosage form | 290mg/kg formulated in standard chow，3 month |
Applications | Early long-term treatment with the CSF1R inhibitor, pexidartinib significantly reduced intraneuronal amyloid, neuritic plaque formation, a reduced amount of toxic prefibrillar oligomers and improved cognitive function in particular associative learning in the contextual fear conditioning of 5XFAD mice. |
human subjects | Eligible patients were 18 years old or older and have a histologically confirmed TGCT that was both unresectable and symptomatic |
Preparation Method | The pooled analysis encompassed 3 groups of pexidartinib-treated patients with TGCT: 1) patients from a phase 1 extension study, 2) patients from ENLIVEN who were randomized to pexidartinib at 1000mg/d for 2 weeks and then 800mg/d, and 3) crossover patients from ENLIVEN receiving pexidartinib at 800mg/d. |
Applications | One hundred thirty patients with TGCT received pexidartinib (median treatment duration, 19 months; range, 1 to 76+ months); 54 (42%) remained on treatment at the end of the analysis (26 months after initial data cut of March 2017). The RECIST overall response rate (ORR) was 60%; the TVS ORR was 65%. The median times to response were 3.4 (RECIST) and 2.8 months (TVS), with 48 of the responding patients (62%) achieving a RECIST partial response by 6 months and with 72 (92%) doing so by 18 months. The median DOR was reached for TVS (46.8 months). Reported TEAEs were mostly low-grade, with hair color changes being most frequent (75%). Most liver abnormalities (92%) were aminotransferase elevations; 4 patients (3%) experienced mixed/cholestatic hepatotoxicity (all within the first 2 months of treatment), which was reversible in all cases (recovery spanned 1-7 months). |
| 产品描述 | Pexidartinib(PLX3397) is an orally administered small molecule tyrosine kinase inhibitor with potent selective activity against the colony-stimulating factor 1(CSF1) receptor(IC50=20nM), KIT proto-oncogene receptor tyrosine kinase(KIT)(IC50 =10nM) and FMS-like tyrosine kinase 3[1,2] Pexidartinib was a stronger KIT inhibitor than imatinib in vitro. Compared pexidartinib and imatinib in vitro against 2 human GIST cell lines that harbor an imatinib-sensitive, activating KIT exon 11 mutation. Indeed, pexidartinib decreased viability in both cell lines with two-fold greater potency than imatinib, with an IC50of 8-18 nM versus 42 nM(p<0.05). At concentrations similar to the IC50of each drug, i.e., 10 and 40 nM, PLX3397 also decreased phospho-KIT relative to total KIT more effectively than imatinib in vitro[3] Pexidartinib is effective in reducing adipose tissue macrophage levels of chow and high fat diet mice without affecting total myeloid cell levels[4]. A research found pexidartinib was well-tolerated in non-human primates(NHPs), with no Grade 3 or Grade 4 toxicities. Pexidartinib has limited CSF penetrance in NHPs following oral administration of a single dose[5] Pexidartinib received its first approval on 2 August 2019 in the USA for the treatment of adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery[2] References: |
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