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Purity: ≥98%
JK184 is a novel and potent Hedgehog (Hh) pathway inhibitor with IC50 of 30 nM in mammalian cells. JK184 can specially inhibit glioma (Gli)-dependent transcriptional activity in the Hedgehog (Hh) pathway in a dose dependent manner and showed great promise for cancer therapeutics. JK184 significantly inhibits proliferation of HUVECs with IC50 of 6.3 μg/mL after three days incubation. To evaluate anti-tumor effect of JK184, MTT assay is conducted in Panc-1 and BxPC-3 cells after administration with indicated concentrations of compounds, half maximal inhibitory concentration (IC50) of JK184 (23.7 ng/mL in anc-1 and 34.3 ng/mL in BxPC-3).
| ln Vitro |
JK184 is intended to counteract Hh signaling by dose-dependently suppressing transcriptional activity that is glioma (Gli)-dependent. After three days incubation, JK184 significantly inhibits HUVEC proliferation, with an IC50 of 6.3 μg/mL. After administering the indicated concentrations of compounds to Panc-1 and BxPC-3 cells, the half maximal inhibitory concentration (IC50) of JK184 is measured (23.7 ng/mL in Anc-1 and 34.3 ng/mL in BxPC-3)[1]. This assay is used to assess the anti-tumor effect of JK184. Compared to MCF10a, MTSV1-7, HMLE-shGFP, and HMLE-pBP cells, claudin-low cell lines are more susceptible to JK184 treatment. In these cell lines, JK184 caused a dose-dependent reduction in the levels of GLI1 (glioma-associated oncogene homolog 1) transcript and protein. The percentage of HMLE-shEcad cells that stained with Annexin-V but tested negative for propidium iodide (PI) (P<0.0001, t test) increases when treated with the IC50 dose of JK184[2].
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| ln Vivo |
JK184 (5 mg/kg, intravenously injected) is a promising candidate for an antitumor drug that targets Hh signaling because it shows good anti-proliferative activity in subcutaneous Panc-1 and BxPC-3 tumor models. JK184, however, has a subpar bioavailability and pharmacokinetic profile [1].
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| References |
[1]. Zhang N, et al. Biodegradable polymeric micelles encapsulated JK184 suppress tumor growth through inhibiting Hedgehog signaling pathway. Nanoscale. 2015 Feb 14;7(6):2609-24.
[2]. Colavito SA, et al. Significance of glioma-associated oncogene homolog 1 (GLI1) expression in claudin-low breast cancer and crosstalk with the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway. Breast Cancer Res. 2014 Sep 25;16 |
| Molecular Formula |
C19H18N4OS
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| Molecular Weight |
350.44
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| CAS # |
315703-52-7
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| Related CAS # |
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| SMILES |
CC1=C(C2=CSC(NC3=CC=C(OCC)C=C3)=N2)N4C=CC=CC4=N1
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.13 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.13 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8536 mL | 14.2678 mL | 28.5356 mL | |
| 5 mM | 0.5707 mL | 2.8536 mL | 5.7071 mL | |
| 10 mM | 0.2854 mL | 1.4268 mL | 2.8536 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
JK184 is more effective at inhibiting EMT cell proliferation.Breast Cancer Res.2014 Sep 25;16(5):444. |
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JK184 inhibits growth of claudin-low cell lines.Breast Cancer Res.2014 Sep 25;16(5):444. |
Decrease inGLI1expression inhibits cell migration and anchorage-independent growth.Breast Cancer Res.2014 Sep 25;16(5):444. |
EMT and claudin-low cells are insensitive to Hedgehog (Hh) pathway inhibitors.Breast Cancer Res.2014 Sep 25;16(5):444. |
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Crosstalk between NFκB and GLI1 signaling pathways.Breast Cancer Res.2014 Sep 25;16(5):444. |
Claudin-low cell lines express higher transcript and protein levels ofGLI1.Breast Cancer Res.2014 Sep 25;16(5):444. |
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