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25mg |
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100mg |
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Voruciclib (formerly known as P1446A-05) is a potent and orally bioavailable CDK4/cyclin-dependent kinase 4 inhibitor with potential anticancer activity. P1446A-05 has CDK inhibitory values ranging from 0.626 nM to 9.1 nM. It specifically prevents the G1-S phase transition mediated by CDK4, which stops cell cycle and stops the growth of cancer cells. The first kinase to activate in response to mitogenic stimulation is the serine/threonine kinase CDK4, which is found in a complex with D-type G1 cyclins. CDK-cyclin complexes have been demonstrated to phosphorylate the retinoblastoma (Rb) transcription factor in early G1, dislodging histone deacetylase (HDAC), and preventing transcriptional repression.
Targets |
CDK9/cyc T2 (Ki = 0.626 nM); CDK9/CycT1 (Ki = 1.68 nM); CDK6/cycD1 (Ki = 2.92 nM); CDK4/Cyc D1 (Ki = 3.96 nM); CDK1/cycB (Ki = 5.4 nM); CDK1/cyc A (Ki = 9.1 nM)
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ln Vitro |
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ln Vivo |
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Cell Assay |
Cell Line: U2932, RIVA, OCI-LY10 cells (ABC subtype), NU-DHL-1, SU-DHL-4, SU-DHL-6 cells (GCB subtype)
Concentration: 0.5 µM, 1 µM, 2 µM, 3 µM, 4 µM, 5 µM Incubation Time: 6 hours Result: Showed targeted downregulation of MCL-1 in both ABC and GCB subtypes. |
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Animal Protocol |
ABC subtypes (U2932, RIVA, OCI-LY10), GCB subtypes (SU-DHL-4, NU-DHL-1) xenografted in Female NOD.CB17-Prkdcscid/NCrHsd mice
200 mpk Oral gavage; U2932, RIVA, SU-DHL-4 (six days per week for 4 weeks), OCI-LY10 (six days per week for 2 weeks), NU-DHL-1 (five days per week for 3 weeks) |
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References |
Molecular Formula |
C22H19CLF3NO5
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Molecular Weight |
469.8412
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Exact Mass |
469.09
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Elemental Analysis |
C, 56.24; H, 4.08; Cl, 7.55; F, 12.13; N, 2.98; O, 17.03
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CAS # |
1000023-04-0
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Related CAS # |
Voruciclib hydrochloride;1000023-05-1;(2S,3R)-Voruciclib hydrochloride;rel-(2S,3R)-Voruciclib;1253731-24-6
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Appearance |
Solid powder
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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
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InChi Key |
MRPGRAKIAJJGMM-OCCSQVGLSA-N
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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+/m1/s1
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Chemical Name |
2-[2-chloro-4-(trifluoromethyl)phenyl]-5,7-dihydroxy-8-[(2R,3S)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl]chromen-4-one
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Synonyms |
1000023-04-0 (free base); 2505206-37-9 (malonate)
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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: ~50 mg/mL (~106.4 mM)
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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 | 2.1284 mL | 10.6419 mL | 21.2838 mL | |
5 mM | 0.4257 mL | 2.1284 mL | 4.2568 mL | |
10 mM | 0.2128 mL | 1.0642 mL | 2.1284 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.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT03547115 | Recruiting | Drug: voruciclib monotherapy Drug: voruciclib and venetoclax |
Follicular Lymphoma (FL) Acute Myeloid Leukemia (AML) |
MEI Pharma, Inc. | May 31, 2018 | Phase 1 |
Comparative kinase profiles of voruciclib and flavopiridol. Sci Rep . 2017 Dec 21;7(1):18007. td> |
Voruciclib at clinically relevant concentrations leads to down regulation of MCL-1 protein (a) Predicted plasma concentrations in humans dosed daily orally with 250 mg voruciclib. Sci Rep . 2017 Dec 21;7(1):18007. td> |
Voruciclib combined with venetoclax leads to model-dependent tumor growth inhibition and long term systemic benefits. Sci Rep . 2017 Dec 21;7(1):18007. td> |