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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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CX-6258 HCl hydrate is a novel, potent, selective and orally bioactive pan-Pim kinase inhibitor with IC50 of 5 nM, 25 nM and 16 nM for Pim1, Pim2, and Pim3, respectively. At CX-6258 showed robust antiproliferative potencies against all cell lines tested derived from human solid tumors and hematological malignancies. In mechanistic cellular assays with MV-4-11 human AML cells, caused dose-dependent inhibition of the phosphorylation of 2 pro-survival proteins, Bad and 4E-BP1, at the Pim kinase specific sites S112 and S65 and T37/46, respectively.
| 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].
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| 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].
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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. |
| 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. |
| References |
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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
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
35
|
| Complexity |
774
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| Defined Atom Stereocenter Count |
0
|
| 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
|
| 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+;;
|
| 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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