| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
JP11646 (0.005 to 10 μM, 72 hours) inhibited the proliferation of all tested cancer cell lines in a concentration-dependent manner, including head and neck cancer FaDu cell line, ovarian cancer SK-OV-3 cell line, breast cancer MDA-MB-231 and BT549 cell lines, prostate cancer PC-3 cell line, liver cancer HepG2 cell line, pancreatic ductal adenocarcinoma MIAPaCa-2 and PANC1 cell lines, colorectal cancer DLD-1 and HT29 cell lines, and non-small cell lung cancer H1650, H661, H460 and A549 cell lines[3]. JP11646 (100-200 nM, 24 hours) selectively downregulated the expression level of PIM2 protein, but had no effect on PIM1 and PIM3, and induced the expression of the apoptosis marker cleaved PARP in MDA-MB-231 and BT549 cells [3]. JP11646 (100-200 nM, 48 hours) significantly increased the apoptosis rate of MDA-MB-231 and BT549 cells [3]. JP11646 (20-200 nM, 0-24 hours) gradually decreased the levels of p4EBP1 (S65) and pBAD (S112) in MM1.S and U266 cells over time, as well as the total level of these proteins. In addition, the level of the potent phosphorylated form of the anti-apoptotic factor MCL1 (Ser159/Thr163) also decreased in a dose-dependent manner [4]. JP11646 (0-1 μM, 72 hours) showed the strongest antiproliferative effect against the MF characteristic cell line MM1.S (GI50 = 5 nM)[4]. JP11646 (20-200 nM, 24 hours) reversed the upregulation of PIM2 in MM1.S and U266 cells induced by recombinant IL-6 (rIL-6), while IL-6 itself did not affect PIM2 mRNA levels[4]. JP11646 (10-20 nM, 48 hours) reversed the chemoprotective effect mediated by CD28 activation or DC co-culture; CTLA4-Ig enhanced the cytotoxicity of JP11646[4]. JP11646 (20-200 nM, 0-24 h) inhibited CD28-induced NF-κB activity in MM1.S and RPMI8226 cells in a dose- and time-dependent manner [4].
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|---|---|
| ln Vivo |
JP11646 (15 mg/kg, intraperitoneal injection, twice a week for 24–40 days) showed broad-spectrum and potent antitumor activity in various xenograft tumor models without significant toxicity [3]. JP11646 (10–15 mg/kg, intraperitoneal injection, 2 or 3 times a week for 48 days) showed strong tumor-dependent antitumor activity in multiple myeloma xenograft models and significantly prolonged the median survival of tumor-bearing mice [4].
|
| Cell Assay |
Western Blot Analysis[3]
Cell Types: MDA-MB-231 cells, BT549 cells Tested Concentrations: 100 nM, 200 nM Incubation Duration: 24 h Experimental Results: Downregulated the protein expression level of PIM2, but had no effect on PIM1 and PIM3, and induced the expression of the apoptosis marker cleaved PARP in MDA-MB-231 and BT549 cells. Apoptosis Analysis[3] Cell Types: MDA-MB-231 cells, BT549 cells Tested Concentrations: 100 nM, 200 nM Incubation Duration: 48 h Experimental Results: Significantly increased the apoptosis rate of MDA-MB-231 and BT549 cells. |
| Animal Protocol |
Animal/Disease Models: Cell suspensions (1×106 of MDA‑MB‑231, 3×106 of MIAPaCa‑2, 2×106 of PANC‑1, 5×106 of HepG2, 5×106 of A549, 5×106 of HT29 and 5×106 of H1650) in a mixture of 50 µl PBS and 50 µl Matrigel were injected subcutaneously into the CB17 SCID mice (female, 6‑8 weeks‑old, weighing 18‑22 g) flanks, or in the case of MDA‑MB‑231 cells, into the abdomen mammary fat pads[3].
Doses: 15 mg/kg Route of Administration: I.p., twice every week (MDA‑MB‑231, 24 days; HepG2, 23 days; MIAPaCa‑2, 29 days; PANC‑1, 40 days; A549, 29 days; H1650, 18 days; HT29, 12 days) Experimental Results: Demonstrated significant tumor growth inhibition in five models: MDA-MB-231 (breast cancer), HepG2 (liver cancer), MIAPaCa-2 (pancreatic cancer), A549 (lung cancer), and H1650 (lung cancer). Did not show significant efficacy in two models (PANC-1 pancreatic cancer and HT29 colorectal cancer). No mice experienced weight loss exceeding 20% or other detectable serious side effects. Animal/Disease Models: SCID/SCIDCBIgh.lblcrTac.Prkdcscid/Ros mice < 5 weeks of age were irradiated at 300 rads using a Mark II Cesium irradiator 24 hours before injecting them with MM1.S cells (5×106) subcutaneously under the skin on the left ventral flank[4]. Doses: 10 mg/kg, 15 mg/kg Route of Administration: I.p., 2 or 3 times a week for 48 days Experimental Results: The relative tumor volume in the 10 mg/kg and 15 mg/kg groups was reduced to 49% and 89% of that in the control group, respectively. The 15 mg/kg group showed a tumor reduction of over 91%. The median survival in the 10 mg/kg group was prolonged to 27 days. The median survival in the 15 mg/kg group was significantly prolonged to 48 days. During the two-week observation period after treatment cessation in the 15 mg/kg group, two of the three surviving mice did not show tumor regeneration. |
| References |
| Molecular Formula |
C25H25N5O2S
|
|---|---|
| Molecular Weight |
459.56
|
| CAS # |
1902983-63-4
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| Appearance |
Typically exists as solids at room temperature
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1760 mL | 10.8800 mL | 21.7599 mL | |
| 5 mM | 0.4352 mL | 2.1760 mL | 4.3520 mL | |
| 10 mM | 0.2176 mL | 1.0880 mL | 2.1760 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.
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