DCLK1-IN-1 is a selective chemical probe with oral bioavailability and in vivo compatibility, targeting the doublecortin like kinase 1 (DCLK1 kinase) domain. It inhibits both DCLK1 and DCLK2 kinases (IC50: DCLK1=9.5/57.2 nM and DCLK2=31/103 nM in binding and kinase assays, respectively). DCLK1-IN-1 demonstrates low toxicity, enabling investigation into DCLK1 biology and its role in cancers such as DCLK1+ pancreatic ductal adenocarcinoma (PDAC) [1].
体内研究
DCLK1-IN-1 exhibits promising pharmacokinetics in mice, characterized by a half-life of 2.09 hours, an area under the curve of 5506 h/ng/mL, and 81% oral bioavailability [1].
体外研究
DCLK1-IN-1 exhibits negligible activity against ERK5, ACK, and LRRK2. It demonstrates potent binding to DCLK1 in HCT116 cells (IC50=279 nM). In PATU-8988T cell lysates and live cells, DCLK1-IN-1 significantly inhibits DCLK1 and weakly inhibits ERK5 [1].
DCLK1-IN-1 细胞实验
Cell Line
Concentration
Treated Time
Description
References
DLD-1 cells
1 μM
24 h
Evaluate the effect of DCLK1-IN-1 on DLD-1 cell proliferation, invasion, and spheroid formation, showing significant inhibition of these processes
Cell Chem Biol. 2020 Oct 15;27(10):1229-1240. e4
DCLK1-FL1Δ (residues 50-686)
20 μM and 40 μM
Confirm the binding of DCLK1-IN-1 to the DCLK1 long isoform
Commun Biol. 2021 Sep 20;4(1):1105
Panc-1 cells
5 μM, 10 μM
48 h
DCLK1-IN-1 effectively blocks EMT process and restores T-cell activity
Transl Oncol. 2022 Mar;17:101317
Huh7 cells
5 μM
48 h
DCLK1-IN-1 inhibited DCLK1 kinase activity, reducing the production of SARS-CoV-2 viral particles and inflammatory cytokine secretion.
J Virol. 2022 Sep 14;96(17):e0096722
Calu3 cells
5 μM and 10 μM
48 h
Inhibition of DCLK1 kinase activity reduced the production of SARS-CoV-2 viral proteins (nucleocapsid and Spike) and decreased the infectivity of viral particles.
J Virol. 2022 Sep 14;96(17):e0096722
Calu-3 cells
5.0 µM
48 h
DCLK1-IN-1 inhibits DCLK1 kinase activity, effectively blocking SARS-CoV-2 replication-transcription processes and reversing virus-induced dysregulation of cell signaling pathways.
J Virol. 2023 Nov 30;97(11):e0119423
HCT116
279 nM
2 h
Evaluate the target engagement of DCLK1-IN-1 in HCT116 cells, showing potent binding to DCLK1.
Nat Chem Biol. 2020 Jun;16(6):635-643
PATU-8902
2.5 μM
24 h
Evaluate the effect of DCLK1-IN-1 on PATU-8902 cells, showing minimal effects on cell viability and gene expression.
Nat Chem Biol. 2020 Jun;16(6):635-643
PATU-8988T
2.5 μM
24 h
Evaluate the effect of DCLK1-IN-1 on PATU-8988T cells, showing minimal effects on cell viability and gene expression.
Nat Chem Biol. 2020 Jun;16(6):635-643
DCLK1-IN-1 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
K18-hACE2 transgenic mice
SARS-CoV-2 infection model
Intraperitoneal injection
10 mg/kg
Once daily for 4 days
DCLK1-IN-1 significantly reduced viral RNA levels, downregulated inflammatory cytokines, restored normal cell signaling pathways, and improved lung pathology.
J Virol. 2023 Nov 30;97(11):e0119423
Nude mice
Ovarian cancer peritoneal metastasis model
Intraperitoneal injection
25 mg/kg
Every other day for 30 days
To evaluate the in vivo efficacy of combining DCLK1-IN-1 with cisplatin, showing significant reduction in tumor growth and peritoneal metastases.
Cancer Lett. 2023 Dec 1;578:216437
Mice
Swiss albino mice
Intravenous and oral
2 mg/kg (IV), 10 mg/kg (PO)
Single dose, 24-hour observation
Evaluate the pharmacokinetic properties of DCLK1-IN-1 in mice, showing a half-life of 2.09 h and 81% oral bioavailability.
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