| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The primary target is cyclin-dependent kinases (CDKs), particularly CDK9. Voruciclib inhibits CDK9, leading to the inhibition of RNA polymerase II-mediated transcription, especially of short-lived anti-apoptotic proteins like Mcl-1. This results in cell cycle arrest and apoptosis in cancer cells.
|
|---|---|
| ln Vitro |
For the treatment of pancreatic cancer, rel-(2S,3R)-Voruciclib (drug B, Formula I) is used in conjunction with gemcitabine and a drug that suppresses EGFR kinase activity [1].
In vitro activity is evaluated through CDK inhibition assays. The IC50 value for CDK9 inhibition is determined using a biochemical assay. Its anti-proliferative activity is assessed against a panel of cancer cell lines, with IC50 values determined by MTT or CellTiter-Glo assays. |
| ln Vivo |
In vivo activity is manifested through its anti-tumor effects in animal models. In xenograft models of various cancers (e.g., mantle cell lymphoma), (2S,3R)-Voruciclib inhibits tumor growth. Its pharmacokinetic properties and safety profile are evaluated.
|
| Enzyme Assay |
The non-cellular kinase inhibition assay involves incubating recombinant CDK9 with (2S,3R)-Voruciclib in the presence of ATP and a substrate peptide. The phosphorylated substrate is detected, and the IC50 is calculated.
|
| Cell Assay |
Cell-based assays involve treating cancer cell lines with (2S,3R)-Voruciclib at varying concentrations. Cell viability is measured by MTT assay. The inhibition of RNA polymerase II phosphorylation and the downregulation of Mcl-1 are assessed by Western blotting.
|
| Animal Protocol |
In vivo animal experiments involve administering (2S,3R)-Voruciclib to tumor-bearing mice via oral gavage. Doses range from 1-50 mg/kg. Tumor growth is monitored by measuring tumor volume. Tumor tissue is analyzed for inhibition of CDK9 and apoptosis markers.
|
| References |
[1]. Veena Agarwal, et al. A synergistic pharmaceutical combination for the treatment of pancreatic cancer. WO2012123889A1.
|
| Molecular Formula |
C22H20CL2F3NO5
|
|---|---|
| Molecular Weight |
506.299115180969
|
| Exact Mass |
469.09
|
| CAS # |
1253731-24-6
|
| Related CAS # |
Voruciclib;1000023-04-0;Voruciclib hydrochloride;1000023-05-1;(2S,3R)-Voruciclib hydrochloride
|
| PubChem CID |
24888038
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
4.1
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
32
|
| Complexity |
750
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CN1CC[C@@H]([C@H]1CO)C2=C(C=C(C3=C2OC(=CC3=O)C4=C(C=C(C=C4)C(F)(F)F)Cl)O)O
|
| InChi Key |
MRPGRAKIAJJGMM-GXTWGEPZSA-N
|
| InChi Code |
InChI=1S/C22H19ClF3NO5/c1-27-5-4-12(14(27)9-28)19-15(29)7-16(30)20-17(31)8-18(32-21(19)20)11-3-2-10(6-13(11)23)22(24,25)26/h2-3,6-8,12,14,28-30H,4-5,9H2,1H3/t12-,14+/m0/s1
|
| Chemical Name |
2-[2-chloro-4-(trifluoromethyl)phenyl]-5,7-dihydroxy-8-[(2S,3R)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl]chromen-4-one
|
| Synonyms |
(2S,3R) Voruciclib (2S,3R) Voruciclib
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 1.9751 mL | 9.8756 mL | 19.7511 mL | |
| 5 mM | 0.3950 mL | 1.9751 mL | 3.9502 mL | |
| 10 mM | 0.1975 mL | 0.9876 mL | 1.9751 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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