GSK3186899 (DDD-853651) (Synonyms: DDD-853651) |
Catalog No.GC33235
One-Click Copy Product Info
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GSK3186899(DDD-853651)(DDD-853651)는 EC50이 1.4 μ인 cdc-2 관련 키나제 12(CRK12)의 억제제입니다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1972617-87-0
Sample solution is provided at 25 µL, 10mM.
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GSK3186899 is an inhibitor of cdc-2-related kinase 12 (CRK12), with an EC50 of 1.4 μM for L. donovani in an intra-macrophage assay.
GSK3186899 (Compound 7) is active against L. donovani in an intra-macrophage assay with an EC50 value of 1.4 μM, and shows good selectivity against mammalian THP-1 host cells (EC50 value>50 μM). This is not as potent as reported data for amphotericin B (EC50 value of 0.07 μM in the intra-macrophage assay), but is comparable to the clinically used drugs miltefosine and paromomycin (EC50 values of 0.9 μM and 6.6 μM, respectively). GSK3186899 is also active in cidal axenic amastigote assay (EC50 value of 0.1 μM). At a concentration of 0.2 μM, GSK3186899 is cytocidal at 96 h; increasing the concentration to 1.8 μM reduced this time to 48 h. GSK3186899 demonstrates a less than 10-fold variation in potency against a panel of Leishmania-derived lines. GSK3186899 is also more active in a panel of Leishmania lines using human peripheral blood mononuclear cells as the host cells[1].
In the mouse model of infection, GSK3186899 demonstrates comparable activity to the front-line drug miltefosine, reducing parasite levels by 99% when dosed orally twice a day for 10 days at 25 mg/kg. The efficacy of treatment is dependent on dose, frequency, and duration (10 days better than 5). The non-clinical safety data for GSK3186899 suggests a suitable therapeutic window for progression into regulatory preclinical studies. Non-GLP preclinical assessment of cardiovascular effects and genotoxicity does not reveal any issues that would prevent further development. In addition, there are no notable adverse effects in a rat seven-day repeat-dose oral toxicity study with respect to clinical chemistry and histopathology at all doses tested. Both the in vivo efficacy and safety profile of GSK3186899 support progression to definitive safety studies[1].
[1]. Wyllie S, et al. Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis. Nature. 2018 Aug;560(7717):192-197.
| Cas No. | 1972617-87-0 | SDF | |
| Synonyms | DDD-853651 | ||
| Canonical SMILES | O=S(CCC(F)(F)F)(N[C@H]1CC[C@H](NC2=NC=C3C(NN=C3N4C[C@H](C)OCC4)=N2)CC1)=O | ||
| Formula | C19H28F3N7O3S | M.Wt | 491.53 |
| Solubility | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0345 mL | 10.1723 mL | 20.3446 mL |
| 5 mM | 406.9 μL | 2.0345 mL | 4.0689 mL |
| 10 mM | 203.4 μL | 1.0172 mL | 2.0345 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 35 reference(s) in Google Scholar.)