| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
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JH-XI-10-02 is a novel, potent and selective PROTAC-based degrader of CDK8, with an DC50 of 159 nM for degradation of CDK8 in Jurkat cells. JH-XI-10-02 causes proteasomal degradation, does not affect CDK8 mRNA levels. JH-XI-10-02 shows no effect on CDK19.
| ln Vitro |
JH-XI-10-02 is a bivalent small chemical modifier that activates the E3 ligase CRL4Cereblon, promoting CDK8 ubiquitination and proteosome modification [1]. JH-XI-10-02 (1 μM) causes partial CDK8 degradation in Jurkat cells after 6 hours of treatment. JH-XI-10-02 (1 μM) leads to considerable degradation of CDK8 after 24 hours of treatment [1]. JH-XI-10-02 causes CDK8 degradation in WT Molt4 cells at 5 μM. CRBN nuLl Molt4 cells do not degrade at any concentration (0.1-5 μM) of WT Molt4 cells or CRBN-added Molt4 cells after 24 hours of CRISPER/CAS9-mediated hybridization [1].
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| Cell Assay |
Blot analysis[1]
Cell Types: Jurkat cells Tested Concentrations: 1 μM Incubation Duration: 6 hrs (hours) and 24 hrs (hours) Experimental Results: CDK8 was partially degraded after 6 hrs (hours) of treatment at 1 μM concentration. CDK8 was Dramatically degraded after 24 hrs (hours) of treatment at 1 μM concentration. Western Blot Analysis [1] Cell Types: WT Molt4 and CRBN null Molt4 cell Tested Concentrations: 0.1, 0.5, 1, 2, 5 μM Incubation Duration: 24 hrs (hours) Experimental Results: CDK8 at 5 μM was degraded in WT Molt4 cells. CRBN null Molt4 cells were not degraded at any concentration. |
| References |
| Molecular Formula |
C53H69N5O9
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|---|---|
| Molecular Weight |
920.1430747509
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| Exact Mass |
919.509
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| CAS # |
2209085-22-1
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| PubChem CID |
133081965
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| Appearance |
Yellow to brown solid powder
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| LogP |
7.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
19
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| Heavy Atom Count |
67
|
| Complexity |
1770
|
| Defined Atom Stereocenter Count |
6
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| SMILES |
O=C(CCOCCOCCOCCOCCNC1=CC=CC2C(N(C(C=21)=O)C1C(NC(CC1)=O)=O)=O)N(C)C1CC[C@@]2(C)[C@@H](C1)CC[C@@H]1[C@H]3CCC(C4=CC=C5C=CN=CC5=C4)[C@@]3(C)CC[C@@H]12
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| InChi Key |
JECHBTRAPARMGI-KMIZWFMDSA-N
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| InChi Code |
InChI=1S/C53H69N5O9/c1-52-19-15-38(32-37(52)9-10-39-42-12-11-41(53(42,2)20-16-43(39)52)35-8-7-34-17-21-54-33-36(34)31-35)57(3)47(60)18-23-64-25-27-66-29-30-67-28-26-65-24-22-55-44-6-4-5-40-48(44)51(63)58(50(40)62)45-13-14-46(59)56-49(45)61/h4-8,17,21,31,33,37-39,41-43,45,55H,9-16,18-20,22-30,32H2,1-3H3,(H,56,59,61)/t37?,38-,39-,41+,42-,43?,45?,52-,53+/m0/s1
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| Chemical Name |
3-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethoxy]-N-[(3S,8R,10S,13S,14S,17S)-17-isoquinolin-7-yl-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]-N-methylpropanamide
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| Synonyms |
JH-XI-10-02JH-XI 10-02JHXI-10-02
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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) |
DMSO : ~100 mg/mL (~108.68 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5.75 mg/mL (6.25 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 57.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0868 mL | 5.4340 mL | 10.8679 mL | |
| 5 mM | 0.2174 mL | 1.0868 mL | 2.1736 mL | |
| 10 mM | 0.1087 mL | 0.5434 mL | 1.0868 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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