JK184 is formulated to antagonize Hedgehog (Hh) signaling by impeding glioma (Gli)-dependent transcriptional activity in a dose-dependent manner. It significantly inhibits the proliferation of human umbilical vein endothelial cells (HUVECs) with an IC50 of 6.3 μg/mL after three days of incubation. To assess the anti-tumor effect of JK184, an MTT assay is conducted in Panc-1 and BxPC-3 cells after treatment with specified compound concentrations, revealing a half-maximal inhibitory concentration (IC50) of JK184 (23.7 ng/mL in Panc-1 and 34.3 ng/mL in BxPC-3)[1]. Claudin-low cell lines exhibit higher sensitivity to JK184 treatment compared to MCF10a, MTSV1-7, or HMLE-shGFP and HMLE-pBP cells. JK184 induces a dose-dependent decrease in glioma-associated oncogene homolog 1 (GLI1) transcript and protein levels in these cells. Treatment with the IC50 dose of JK184 increases the proportion of HMLE-shEcad cells staining positive for Annexin-V but negative for propidium iodide (PI) (P<0.0001)[2].
体内研究
JK184 (5 mg/kg, injected intravenously) demonstrates significant anti-proliferative effects in subcutaneous Panc-1 and BxPC-3 tumor models, positioning it as a promising candidate for targeting Hh signaling in anticancer therapy. However, JK184 suffers from limitations in its pharmacokinetic profile and bioavailability[1].
体外研究
JK184 is formulated to antagonize Hedgehog (Hh) signaling by impeding glioma (Gli)-dependent transcriptional activity in a dose-dependent manner. It significantly inhibits the proliferation of human umbilical vein endothelial cells (HUVECs) with an IC50 of 6.3 μg/mL after three days of incubation. To assess the anti-tumor effect of JK184, an MTT assay is conducted in Panc-1 and BxPC-3 cells after treatment with specified compound concentrations, revealing a half-maximal inhibitory concentration (IC50) of JK184 (23.7 ng/mL in Panc-1 and 34.3 ng/mL in BxPC-3)[1].
Claudin-low cell lines exhibit higher sensitivity to JK184 treatment compared to MCF10a, MTSV1-7, or HMLE-shGFP and HMLE-pBP cells. JK184 induces a dose-dependent decrease in glioma-associated oncogene homolog 1 (GLI1) transcript and protein levels in these cells. Treatment with the IC50 dose of JK184 increases the proportion of HMLE-shEcad cells staining positive for Annexin-V but negative for propidium iodide (PI) (P<0.0001)[2].
JK184 induced apoptosis in HCT116 cells, with an apoptosis rate of approximately 28.8%.
J Transl Med. 2023 Jan 13;21(1):23
MDA-MB-231 cells
1 μM
24 hours
JK184 induced apoptosis in MDA-MB-231 cells, with an apoptosis rate of approximately 42.04%.
J Transl Med. 2023 Jan 13;21(1):23
MDA.MB.436 cells
0.002 μM
72 hours
JK184 inhibited the proliferation of MDA.MB.436 cells and reduced GLI1 transcript and protein levels.
Breast Cancer Res. 2014 Sep 25;16(5):444
BT549 cells
0.002 μM
72 hours
JK184 inhibited the proliferation of BT549 cells and reduced GLI1 transcript and protein levels.
Breast Cancer Res. 2014 Sep 25;16(5):444
HMLE-Snail cells
0.004 μM
72 hours
JK184 inhibited the proliferation of HMLE-Snail cells and reduced GLI1 transcript and protein levels.
Breast Cancer Res. 2014 Sep 25;16(5):444
HMLE-shEcad cells
0.004 μM
72 hours
JK184 inhibited the proliferation of HMLE-shEcad cells and reduced GLI1 transcript and protein levels.
Breast Cancer Res. 2014 Sep 25;16(5):444
Hep2 cells
10 μM
48 hours
To evaluate the effect of JK184 alone or in combination with shEGFR on the viability of Hep2 cells. Results showed that the combination of JK184 and shEGFR significantly reduced cell viability.
Int J Clin Exp Pathol. 2017 Sep 1;10(9):9816-9828
FaDu cells
10 μM
48 hours
To evaluate the effect of JK184 alone or in combination with shEGFR on the viability of FaDu cells. Results showed that the combination of JK184 and shEGFR significantly reduced cell viability and induced a higher apoptosis rate.
Int J Clin Exp Pathol. 2017 Sep 1;10(9):9816-9828
786-O cells
10 nM
48 hours
Inhibited the Hedgehog signaling pathway, decreased the expression levels of SHH, SMO, and GLi1, and increased the expression levels of PTCH2 and SUFU.
Cancer Cell Int. 2023 Dec 12;23(1):319
B7-H3 CAR T cells
1 μM
24 hours
JK184 modulates B7-H3 CAR T cells to an effector memory phenotype and promotes cytokine secretion.
J Transl Med. 2023 Jan 13;21(1):23
JK184 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
M-NSG mice
MDA-MB-231-FFluc and HCT116-FFluc xenograft models
Intraperitoneal injection
5 mg/kg
10 consecutive days
JK184 combined with B7-H3 CAR T cells significantly inhibited tumor growth and prolonged survival in mice.
J Transl Med. 2023 Jan 13;21(1):23
Balb/c nude mice
Maxillary sinus tumor model
Subcutaneous injection
10 mg/kg body weight
Three times a week, continuous treatment
To evaluate the inhibitory effect of JK184 alone or in combination with shEGFR on tumor growth. Results showed that the inhibitory rate of the combined therapy was significantly higher than that of single treatments.
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