| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
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| Targets |
Akt2 6 nM (IC50) PKA 168 nM (IC50) p70S6K 120 nM (IC50) Autophagy Apoptosis
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| ln Vitro |
CCT128930 hydrochloride's growth inhibition GI50 values for PTEN-deficient human tumor cell lines are 6.3 μM for U87MG human glioblastoma cells, 0.35 μM for LNCaP human prostate cancer cells, and 1.9 μM for PC3 human prostate cancer cells[1]. AKT phosphorylation at serine 473 is first induced up to 20 μM in response to CCT128930 (0.1-60 μM; 1 hour; U87MG human glioblastoma cells) hydrochloride, and then decreases at higher concentrations[1]. With essentially constant levels of the corresponding total proteins and GAPDH, CCT128930 hydrochloride inhibits the downstream target, pSer235/236 S6RP, at ≥10 μM, and the direct substrates of AKT (Ser9 GSK3β, pThr246 PRAS40, and pT24 FOXO1/p32 FOXO3a) at ≥5 μM[1]. After half an hour, pSer473 AKT phosphorylation increases in response to CCT128930 (18.9 μM; U87MG human glioma cells) hydrochloride, and this effect lasts for 48 hours. Between 8 and 48 hours after therapy, the total AKT protein signal gradually drops[1]. In HepG2 and A549 cells, CCT128930 hydrochloride (0–10 μM; 24 hours) phosphorylates Akt more than it inhibits. By downregulating cyclin D1 and Cdc25A and upregulating p21, p27, and p53, CCT128930 (0–20 μM; 24 hours) hydrochloride prevents cell division. Hydrochloride of CCT128930 (20 μM) activates caspase-3, caspase-9, and PARP, which in turn causes cell death. HepG2 cells' phosphorylation of ERK and JNK is increased by CCT128930 hydrochloride (0–20 μM; 24 hours). HepG2 cells' DNA damage response is activated by CCT128930 (0–20 μM; 24-hour exposure), which is characterized by the phosphorylation of H2AX, ATM (ataxia-telangiectasia mutant), Chk1, and Chk2[2].
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| ln Vivo |
In U87MG and BT474 human breast cancer xenografts, CCT128930 hydrochloride (25 or 40 mg/kg; intraperitoneal daily or twice daily for 5 days) exhibits antitumor activities[1]. The pharmacokinetic parameters of CCT128930 (25 mg/kg) in CrTacNCr- Fox1nu mice are summarized as follows: Tissue Route T1/2 (h) Tmax (h) Cmax (μM) Vss (L) Cl (L/h) AUC0-∞ (μMh) Bioavailability (%) Plasma iv 0.95 0.083 6.36 0.25 0.325 4.62 100 MCE has not independently confirmed the clearance. precision of these techniques. They are merely meant to be used as references.
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| Animal Protocol |
Animal/Disease Models: 6-8 weeks old female CrTacNCr-Fox1nu (nude) mice[1]
Doses: 25 mg/kg (U87MG human glioblastoma xenografts) or 40 mg/kg (BT474 human breast cancer xenografts) Route of Administration: ip daily for 5 days (U87MG human glioblastoma xenografts); ip twice (two times) daily for 5 days (BT474 human breast cancer xenografts) Experimental Results: Giving a treated:control (T/C) ratio on day 12 of 48%. There was no weight loss associated with this regime in U87MG human glioblastoma xenografts. Had a profound antitumor effect with complete growth arrest and a T/C ratio of 29% on day 22. This regimen was associated with minimal weight loss, with a nadir of only 94.8% of the initial body weight on day 15 of treatment in BT474 human breast cancer xenografts. |
| References |
[1]. Yap TA et al. Preclinical pharmacology, antitumor activity, and development of pharmacodynamic markers for the novel, potent AKT inhibitor CCT128930. Mol Cancer Ther. 2011 Feb;10(2):360-71.
[2]. Wang FZ, et al. CCT128930 induces cell cycle arrest, DNA damage, and autophagy independent of Akt inhibition. Biochimie. 2014;103:118-125. |
| Molecular Formula |
C18H21CL2N5
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|---|---|
| Molecular Weight |
378.30
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| CAS # |
2453324-32-6
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| Related CAS # |
CCT128930;885499-61-6
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| SMILES |
ClC1C=CC(=CC=1)CC1(CCN(C2C3C=CNC=3N=CN=2)CC1)N.Cl
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| Solubility (In Vitro) |
DMSO : 20 mg/mL (52.87 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (5.29 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 20.0 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. Solubility in Formulation 2: ≥ 2 mg/mL (5.29 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline 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 | 2.6434 mL | 13.2170 mL | 26.4340 mL | |
| 5 mM | 0.5287 mL | 2.6434 mL | 5.2868 mL | |
| 10 mM | 0.2643 mL | 1.3217 mL | 2.6434 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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