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| 25mg |
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| 50mg |
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| Targets |
CX-6258 targets Pim-1, Pim-2, and Pim-3 kinases. Pim kinases are serine/threonine kinases that play critical roles in cell survival, proliferation, and differentiation. They are frequently overexpressed in various hematological malignancies and solid tumors. CX-6258 inhibits Pim-1, Pim-2, and Pim-3 with IC₅₀ values of 5 nM, 25 nM, and 16 nM, respectively. The compound also inhibits Flt-3 with an IC₅₀ of 0.134 μM and Pim-3 with an IC₅₀ of 0.016 μM.
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| ln Vitro |
Two pro-survival proteins, Bad and 4E-BP1, are phosphorylated at Pim kinase specific sites S112, S65, and T37/46, respectively, and are inhibited by CX-6258 in a dose-dependent manner[1]. In PC3 cells, CX-6258 treatment (12 mM, 3 h) reduces steady-state levels of ectopic NKX3.1[2]. The half-life of NKX3.1 is significantly shortened by CX-6258 treatment[2].
CX-6258 inhibits Flt-3 and Pim-3 with IC₅₀ values of 0.134 and 0.016 μM, respectively. It has strong antiproliferative potencies against human solid tumors and hematological malignancies. The compound's excellent biochemical potency and kinase selectivity make it a valuable tool for studying Pim kinase biology. Inhibition of Pim kinases is expected to have beneficial effects in cancer therapy. CX-6258 is used in preclinical cancer research to study hematologic malignancies and solid tumors. |
| ln Vivo |
Two Pim kinases-driven tumor models demonstrate strong in vivo effectiveness for CX-6258 (50-100 mg/kg; po; daily; for 21 days)[1].
In vivo, CX-6258 hydrochloride hydrate is orally efficacious. The compound has been used in preclinical cancer research to study hematologic malignancies and solid tumors, as well as to evaluate combination therapies. Its oral bioavailability and efficacy make it suitable for in vivo studies. However, specific in vivo efficacy data have not been detailed in the available literature. Further studies are needed to fully characterize its in vivo activity. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for CX-6258 typically involve kinase inhibition assays using purified recombinant Pim-1, Pim-2, and Pim-3 enzymes. The compound is incubated with the kinase, ATP, and a suitable peptide substrate in kinase buffer. Kinase activity is measured by incorporation of ³²P-ATP into the substrate or by using a luminescent kinase assay. IC₅₀ values are determined by measuring kinase activity at various inhibitor concentrations and fitting the data to a dose-response curve. The compound's selectivity is assessed by screening against a panel of kinases.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: MV-4-11 human AML cells. Tested Concentrations: 0.1 μM, 1 μM, 10 μM. Incubation Duration: 2 hrs (hours). Experimental Results: Caused dose dependent inhibition of the phosphorylation of two pro-survival proteins, Bad and 4E-BP1, at the Pim kinase specific sites S112 and S65 and T37/46, respectively. In vitro cell-based assays for CX-6258 typically employ cancer cell lines, including hematological malignancy cell lines (e.g., MV4-11, K562, U937) and solid tumor cell lines. Cells are cultured in appropriate medium and treated with various concentrations of the compound for 48-72 hours. Cell viability is assessed by MTT, CCK-8, or CellTiter-Glo assays. Apoptosis is evaluated by Annexin V/PI staining and flow cytometry. Proliferation and signaling pathways are assessed by Western blot analysis of phosphorylated downstream targets. |
| Animal Protocol |
Animal/Disease Models: Nude mice, MV-4-11 xenograft models[1]
Doses: 50 mg/kg, 100 mg/kg. Route of Administration: Oral administration; one time/day; over a period of 21 days. Experimental Results: demonstrated dose dependent efficacy, with a 50 mg/kg dose producing 45% tumor growth inhibition (TGI) and a 100 mg/kg dose producing 75% TGI. In vivo animal studies with CX-6258 typically involve oral administration to rodents in xenograft models of hematological malignancies and solid tumors. The compound is administered at various doses (typically 10-100 mg/kg) once or twice daily. Tumor volume is measured regularly, and animals are monitored for body weight and signs of toxicity. At study termination, tumors are collected for histopathological and biochemical analysis. The compound's oral efficacy is a key feature of these studies. |
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of CX-6258 hydrochloride hydrate have been partially characterized. The compound is orally efficacious, indicating good oral bioavailability. However, specific PK parameters such as half-life, Cₘₐₓ, Tₘₐₓ, and bioavailability have not been detailed in the available literature. The compound's hydrochloride hydrate salt form is designed to improve solubility and stability. Further PK studies are needed.
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| Toxicity/Toxicokinetics |
The toxicity profile of CX-6258 hydrochloride hydrate has not been extensively characterized in preclinical studies. The compound is intended for research use only and is not approved for human therapeutic applications. Standard safety precautions should be followed when handling this compound. No specific toxicology data are available in the published literature.
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| References |
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| Additional Infomation |
CX-6258 hydrochloride hydrate is a research-grade pan-Pim kinase inhibitor. It inhibits Pim-1, Pim-2, and Pim-3 with IC₅₀ values of 5 nM, 25 nM, and 16 nM, respectively. The compound has strong antiproliferative activity against human solid tumors and hematological malignancies. It is orally efficacious and used in preclinical cancer research. The compound is not an approved therapeutic drug and has no clinical applications. Molecular formula: C₂₆H₂₇Cl₂N₃O₄; molecular weight: 516.42. It should be stored appropriately.
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| Molecular Formula |
C26H27CL2N3O4
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|---|---|
| Molecular Weight |
516.416284799576
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| Exact Mass |
515.137
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| CAS # |
1353858-99-7
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| Related CAS # |
CX-6258;1202916-90-2
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| PubChem CID |
74892460
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| Appearance |
Yellow to orange solid powder
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| LogP |
5.621
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
35
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| Complexity |
774
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1CCCN(CC1)C(=O)C2=CC=CC(=C2)C3=CC=C(O3)/C=C/4\C5=C(C=CC(=C5)Cl)NC4=O.O.Cl
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| InChi Key |
ZOZTWDKBSOVPDP-LLDDCTHSSA-N
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| InChi Code |
InChI=1S/C26H24ClN3O3.ClH.H2O/c1-29-10-3-11-30(13-12-29)26(32)18-5-2-4-17(14-18)24-9-7-20(33-24)16-22-21-15-19(27)6-8-23(21)28-25(22)31;;/h2,4-9,14-16H,3,10-13H2,1H3,(H,28,31);1H;1H2/b22-16+;;
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| Chemical Name |
(3E)-5-chloro-3-[[5-[3-(4-methyl-1,4-diazepane-1-carbonyl)phenyl]furan-2-yl]methylidene]-1H-indol-2-one;hydrate;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
DMSO : ~25 mg/mL (~48.41 mM)
H2O : ~7.14 mg/mL (~13.83 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.84 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 (4.84 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. View More
Solubility in Formulation 3: 20 mg/mL (38.73 mM) in 20% HP-β-CD in Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; Need ultrasonic and warming and heat to 48°C. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9364 mL | 9.6820 mL | 19.3641 mL | |
| 5 mM | 0.3873 mL | 1.9364 mL | 3.8728 mL | |
| 10 mM | 0.1936 mL | 0.9682 mL | 1.9364 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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