Limantrafin (CB-103) is a pioneering, orally bioavailable inhibitor of protein-protein interaction (PPI) targeting the NOTCH transcriptional activation complex. Limantrafin exhibits antitumor efficacy[1][2][3][4].
体内研究
Limantrafin suppresses NOTCH-dependent cellular processes in mice[2].
Limantrafin impedes the in vivo growth of patient-derived xenograft (PDX) models of T-ALL[2].
Limantrafin (25 mg/kg; i.p./pO.; 2x daily; for 2 weeks) suppresses the growth of triple negative breast cancer resistant to GSI/Mab[3].
Limantrafin demonstrates antitumor efficacy in xenograft models of human T-ALL and mouse mammary tumors[3].
体外研究
Limantrafin functions as a broad-spectrum NOTCH inhibitor by targeting the NOTCH transcriptional activation complex[2].
Limantrafin is capable of inhibiting NOTCH signaling in human T cell acute lymphoblastic leukemia cancer cell lines[2].
Limantrafin demonstrates antitumor effectiveness in T-ALL cell lines resistant to GSI[2].
CB-103 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HeLa cells
0.9 to 3.9 µM (IC50)
24 hours
CB-103 inhibits Notch signaling, including Notch1, Notch2, Notch3, and Notch4-mediated signaling
Proc Natl Acad Sci U S A. 2020 Jul 14;117(28):16292-16301.
HEK293 cells
0.5 and 2.5 µM
48 hours
To evaluate the effect of CB-103 on the Notch signaling pathway, results showed a dose-dependent reduction in luciferase signal.
Sci Rep. 2023 Aug 22;13(1):13700.
HCC1187 TNBC cells
10 µM
6 days
CB-103 inhibits growth of GSI-resistant tumor cells
Proc Natl Acad Sci U S A. 2020 Jul 14;117(28):16292-16301.
WHM20
1 µM and 5 µM
7 days
To evaluate the effect of CB-103 alone or in combination with fulvestrant on mammosphere formation, results showed that CB-103 significantly inhibited mammosphere formation.
Cancers (Basel). 2023 Aug 3;15(15):3957.
T47D/PKCα
1 µM and 5 µM
7 days
To evaluate the effect of CB-103 alone or in combination with fulvestrant on mammosphere formation, results showed that CB-103 significantly inhibited mammosphere formation.
Cancers (Basel). 2023 Aug 3;15(15):3957.
HCC1187
150 nM to 10 µM
72 hours
To evaluate the synergistic effects of CB-103 with various anti-neoplastic drugs, results showed that CB-103 exhibited synergy with paclitaxel in HCC1187 cells.
Cancers (Basel). 2023 Aug 3;15(15):3957.
MCF-7
150 nM to 10 µM
72 hours
To evaluate the synergistic effects of CB-103 with various anti-neoplastic drugs, results showed that CB-103 exhibited synergy with fulvestrant and paclitaxel in MCF-7 cells.
Cancers (Basel). 2023 Aug 3;15(15):3957.
RPMI-8402 T-ALL cells
10 µM
72 hours
CB-103 induces cell cycle arrest and apoptosis, impairing proliferation
Proc Natl Acad Sci U S A. 2020 Jul 14;117(28):16292-16301.
CB-103 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
HCC1187 xenograft model
Oral
25 mg/kg
Twice daily for 15 days
CB-103 significantly inhibits tumor growth and reduces tumor burden
Proc Natl Acad Sci U S A. 2020 Jul 14;117(28):16292-16301.
Nude mice
PDX CTG-2308 (ER+ ESR1 wild type)
Subcutaneous injection
40 mg/kg
Once daily for 5 days
To evaluate the effect of CB-103 in combination with fulvestrant on ER+ breast cancer models, results showed that combination therapy significantly delayed tumor growth.
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