Tambiciclib dimaleate
Based on 1 publication(s) in Google Scholar
Tambiciclib (GFH009, JSH-009) dimaleate is an orally active, highly potent and selective CDK9 inhibitor (IC50 = 1 nM), demonstrating >200-fold selectivity over other CDKs, >100-fold selectivity over DYRK1A/B, and excellent selectivity over 468 kinases/mutants. Tambiciclib dimaleate demonstrates potent in vitro and in vivo antileukemic efficacy in acute myeloid leukemia (AML) mouse models by inhibiting RNA Pol II phosphorylation, downregulating MCL1 and MYC, and inducing apoptosis. Tambiciclib dimaleate can be used for AML research.
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- Pureté: 99.53%
- CAS No.: 2559759-04-3
- Formule: C33H43ClN6O10S
- Masse moléculaire:751.25
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Stockage:
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) Tambiciclib dimaleate
MoreVoir tous les produits spécifiques à Isoform Caspase
MoreVoir tous les produits spécifiques à Isoform DNA/RNA Synthesis
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Activité biologique
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CDK9/cyclinT1 1 nM (IC50) |
CDK1/cyclinB 5410 nM (IC50) |
CDK2/cyclinA 6850 nM (IC50) |
CDK3/cyclin E1 >10,000 nM (IC50) |
Cdk5/p25 6950 nM (IC50) |
CDK7/Cyclin H/MNAT1 3700 nM (IC50) |
CDK8/cyclin C >10,000 nM (IC50) |
CDK11 >10,000 nM (IC50) |
CDK14/Cyclin Y 2710 nM (IC50) |
CDK16/Cyclin Y 195 nM (IC50) |
Tambiciclib (JSH009) dimaleate (72 h) potently inhibits the growth of diverse AML cell lines and patient-derived primary cells (GI50 < 50 nM), but is far less potent against normal peripheral blood mononuclear cells (PBMCs) (GI50 > 10 μM), supporting a favorable safety profile[1].
Tambiciclib dimaleate (0.03-3 μM, 2 h) potently and dose-dependently inhibits the phosphorylation of RNA Pol II at Ser2 (EC50 < 300 nM) in OCI-AML-3, MV4-11, and HL-60 cells, while showing no effect on the CDK7-mediated phosphorylation of RNA Pol II at Ser5 or CDK9 at Thr186, confirming its high selectivity over CDK7[1].
Tambiciclib dimaleate (0.03-0.1 μM, 10 h) downregulates MCL1 and MYC expression at the transcriptional level alongside a broader reduction in overall transcription in MV4-11 cells[1].
Tambiciclib dimaleate (0.01-0.1 μM, 24 h) induces apoptosis in OCI-AML-3, MV4-11, and HL-60 cell lines, as evidenced by the cleavage of caspase-3 and PARP[1].
Tambiciclib dimaleate (0.01-0.05 μM, 24 h) has no effect on the cell cycle distribution of MV4-11 and OCI-AML-3 cells, consistent with the lack of significant changes in the expression of key cell cycle regulators (E2F1, Cyclin D1, CDC2) in MV4-11 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:OCI-AML3, MV4-11, and HL-60 cells
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Concentration:0.01, 0.03, and 0.1 μM
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Incubation Time:24 h
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Result:Increased cleaved-caspase3 and cleaved-PARP levels in all three cell lines.
Elicited a markedly weaker PARP cleavage signal in OCI-AML3 cells compared to MV4-11 and HL-60 cells.
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Cell Line:OCI-AML-3, MV4-11, and HL-60 cells
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Concentration:0.03, 0.1, 0.3, 1, and 3 μM
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Incubation Time:2 h
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Result:Reduced p-RNA Pol II Ser2 and levels in a dose-dependent manner.
Did not affect the phosphorylation levels of RNA Pol II Ser5 or CDK9 Thr186, which are controlled by CDK7, even at a concentration of 3 μM.
Reduced MCL-1 and C-MYC protein levels.
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Cell Line:MV4-11 cells
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Concentration:0.03 and 0.1 μM
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Incubation Time:10 h
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Result:Decreased MYC and MCL1 mRNA levels in MV4-11 cells.
Tambiciclib dimaleate (10 and 15 mg/kg, P.O., daily until endpoint) dose-dependently prolongs overall survival in the MV4-11 cell-derived engraftment mouse model[1].
Tambiciclib dimaleate (10 and 20 mg/kg, P.O., daily for approximately 2 weeks) displays dose-dependent efficacy against antitumor progression in an AML patient-derived xenograft (PDX) mouse model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Balb/c nu mice subcutaneously injected with MV4-11 cells[1]
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Dosage:10 and 20 mg/kg
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Administration:p.o., daily for 3 weeks
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Result:Inhibited tumor growth with TGI of 25.2% at 10 mg/kg.
Almost completely suppressed tumor progression (TGI = 98.7%) at a 20 mg/kg dosage.
Revealed no apparent behavioral changes or body weight loss in mice.
Suppressed proliferation (Ki67) and induced apoptosis in a dose dependent manner.
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Animal Model:Female NOD-SCID mice (5 weeks old) intravenously injected with MV4-11 cells[1]
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Dosage:10 and 15 mg/kg
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Administration:p.o., daily until endpoint
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Result:Prolonged overall survival in a dose-dependent manner.
Achieved almost 200 days of survival in mice at 15 mg/kg.
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Animal Model:Female NCG mice (5 weeks old) subcutaneously implanted with AML patient tumors[1]
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Dosage:10 and 20 mg/kg
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Administration:p.o., daily for approximately 2 weeks
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Result:Resulted in a TGI of 53.4% without any apparent overall toxicity at 20 mg/kg.
Displayed dose-dependent efficacy against antitumor progression.
Downregulated the phosphorylation of RNA Pol II and Mcl1/MYC protein levels.
Chemical Information
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CAS No. 2559759-04-3
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Appearance Solid
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Masse moléculaire 751.25
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Formule C33H43ClN6O10S
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Color Off-white to light yellow
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SMILES
COC[C@@H](C)N[C@@H](CC1)CC[C@H]1NC2=CC(C3=CSC(NCC4(CCOCC4)C#N)=N3)=C(Cl)C=N2.OC(/C=C\C(O)=O)=O.OC(/C=C\C(O)=O)=O
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Synonyms
GFH009 dimaleate; JSH-009 dimaleate; SLS009 dimaleate
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Publications (1)
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Journal Impact Factor
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Most Recent
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Acta Pharm Sin B
2023 Sep;13(9):3694-3707. PMID: 37719386
Solvant et solubilité
DMSO : 100 mg/mL (133.11 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (3.33 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (3.33 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureté et documentation
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Fiche technique (285 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instruction de manipulation (2659 KB)
Références
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.3311 mL | 6.6556 mL | 13.3111 mL | 33.2779 mL |
| 5 mM | 0.2662 mL | 1.3311 mL | 2.6622 mL | 6.6556 mL | |
| 10 mM | 0.1331 mL | 0.6656 mL | 1.3311 mL | 3.3278 mL | |
| 15 mM | 0.0887 mL | 0.4437 mL | 0.8874 mL | 2.2185 mL | |
| 20 mM | 0.0666 mL | 0.3328 mL | 0.6656 mL | 1.6639 mL | |
| 25 mM | 0.0532 mL | 0.2662 mL | 0.5324 mL | 1.3311 mL | |
| 30 mM | 0.0444 mL | 0.2219 mL | 0.4437 mL | 1.1093 mL | |
| 40 mM | 0.0333 mL | 0.1664 mL | 0.3328 mL | 0.8319 mL | |
| 50 mM | 0.0266 mL | 0.1331 mL | 0.2662 mL | 0.6656 mL | |
| 60 mM | 0.0222 mL | 0.1109 mL | 0.2219 mL | 0.5546 mL | |
| 80 mM | 0.0166 mL | 0.0832 mL | 0.1664 mL | 0.4160 mL | |
| 100 mM | 0.0133 mL | 0.0666 mL | 0.1331 mL | 0.3328 mL |
Tambiciclib dimaleate Related Classifications
HY-X0009A Related Classifications
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