KT-276 is a derivative of PKT-185, designed as an orally available and selective inhibitor targeting the nuclear export (SINE) function. Specifically, it acts as a CRM1 antagonist, irreversibly binding to and inhibiting the CRM1 protein, which plays a crucial role in the nuclear export of numerous proteins and RNA[1].
KPT-276 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human myeloma cell lines (HMCLs)
15.625 nM to 1000 nM
72 hours
KPT-276 significantly reduced the viability of 12 HMCLs, with a median IC50 value of approximately 160 nM.
Leukemia. 2013 Dec;27(12):2357-65.
SKBR3
10 μM
24 hours
To evaluate the effect of KPT-276 on SKBR3 cell apoptosis, results showed that KPT-276 significantly induced apoptosis
Mol Cancer Ther. 2014 Mar;13(3):675-86.
SKBR3
0.01-100 μM
72 hours
To evaluate the effect of KPT-276 on SKBR3 cell growth, results showed that KPT-276 significantly inhibited cell growth
Mol Cancer Ther. 2014 Mar;13(3):675-86.
MDA-MB-231
0.01-100 μM
72 hours
To evaluate the effect of KPT-276 on MDA-MB-231 cell growth, results showed that KPT-276 significantly inhibited cell growth
Mol Cancer Ther. 2014 Mar;13(3):675-86.
MCF7
0.01-100 μM
72 hours
To evaluate the effect of KPT-276 on MCF7 cell growth, results showed that KPT-276 significantly inhibited cell growth
Mol Cancer Ther. 2014 Mar;13(3):675-86.
WSU-FSCCL
0–150 nM
72 hours
Evaluate the cytotoxicity and apoptosis effects of KPT-276 in combination with DEX or EVER, showing significantly enhanced apoptosis
Cancer Lett. 2016 Dec 28;383(2):309-317.
WSU-DLCL2
0–150 nM
72 hours
Evaluate the cytotoxicity and apoptosis effects of KPT-276 in combination with DEX or EVER, showing significantly enhanced apoptosis
Cancer Lett. 2016 Dec 28;383(2):309-317.
MesoII cells
0.36 ± 0.04 μmol/L (IC50)
72 hours
To evaluate the inhibitory effect of KPT-276 on DMPM cell growth, results showed that KPT-276 significantly inhibited the growth of MesoII cells with an IC50 value of 0.36 ± 0.04 μmol/L
Oncotarget. 2015 May 30;6(15):13119-32.
STO cells
0.24 ± 0.02 μmol/L (IC50)
72 hours
To evaluate the inhibitory effect of KPT-276 on DMPM cell growth, results showed that KPT-276 significantly inhibited the growth of STO cells with an IC50 value of 0.24 ± 0.02 μmol/L
initial dose 50 mg/kg, escalated to 75 mg/kg after one week
3 times per week (Monday, Wednesday, Friday), continued treatment
Evaluate the in vivo efficacy of KPT-276 in a GBM xenograft model, showing significant tumor growth suppression and prolonged animal survival
Neuro Oncol. 2015 May;17(5):697-707.
Mice
Experimental autoimmune encephalomyelitis (EAE)
Oral gavage
75 mg/kg
Every other day for 12 days
To evaluate the therapeutic effect of KPT-276 in the EAE model, results showed significant attenuation of disease progression and preservation of axonal integrity.
Nat Neurosci. 2015 Apr;18(4):511-20.
ICR-SCID mice
WSU-DLCL2 subcutaneous tumor model and WSU-FSCCL systemic model
Oral
75 and 150 mg/kg
Once daily for ten consecutive days with a one day break prior to start of a new cycle
Evaluate the anti-tumor activity of KPT-276 in NHL xenograft models, showing comparable or superior anti-tumor potential to CHOP regimen
Cancer Lett. 2016 Dec 28;383(2):309-317.
NOD/SCID mice
A375 or CHL-1 human melanoma xenograft models
Oral
75 mg/kg
Three times weekly until tumor volume reached 1500 mm³
KPT-276 significantly inhibited the growth of A375 and CHL-1 human melanoma xenografts.
PLoS One. 2014 Jul 24;9(7):e102983
NOD-SCID mice
H1975 cell xenograft model
Oral
100 mg/kg
3 times a week for 3 weeks
To examine the efficacy and side effects of KPT-276 in vivo. Results showed that KPT-276 significantly inhibited tumor growth with no significant mouse body weight loss or other side effects.
PLoS One. 2014 Mar 4;9(3):e89848
Nude mice
Subcutaneous STO xenograft model
Oral
50 mg/kg
5 days a week for 3 weeks
To evaluate the anti-tumor activity of KPT-276 in subcutaneous STO xenograft model, results showed that KPT-276 significantly inhibited tumor growth with a tumor volume inhibition rate of 84%
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