| Identification | Back Directory | [Name]
4-(4-Chlorobenzyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-amine hydrochloride | [CAS]
2453324-32-6 | [Synonyms]
CCT128930 hydrochloride
CCT128930 hydrochloride(885499-61-6 Free base)
4-(4-Chlorobenzyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-amine hydrochloride
CCT128930 hydrochloride,U87MG,cell,phosphorylation,selective,DNA damage,CCT128930,glioblastoma,Autophagy,arrest,Akt,breast cancer,Inhibitor,BT474,PTEN,Apoptosis,growth,PKB,inhibit,CCT 128930,CCT-128930 hydrochloride,cycle,CCT-128930,Protein kinase B | [Molecular Formula]
C18H21Cl2N5 | [MDL Number]
MFCD32667039 | [MOL File]
2453324-32-6.mol | [Molecular Weight]
378.3 |
| Hazard Information | Back Directory | [Uses]
CCT128930 hydrochloride is a potent and selective inhibitor of AKT (IC50=6 nM). CCT128930 hydrochloride has 28-fold selectivity over the closely related PKA kinase (IC50=168 nM) through the targeting of Met282 of AKT (Met173 of PKA-AKT chimera), as well as 20-fold selectivity over p70S6K (IC50=120 nM). CCT128930 hydrochloride induces cell cycle arrest, DNA damage, and autophagy. Antitumor activity[1][2]. | [in vivo]
CCT128930 (25 or 40 mg/kg; i.p. daily or twice daily for 5 days) hydrochloride shows antitumor activities in U87MG and BT474 human breast cancer xenografts[1].
Summary of the pharmacokinetic parameters of CCT128930 (25 mg/kg) in CrTacNCr-Fox1nu mice[1]
| Tissue | Route | T1/2
(h) | Tmax
(h) | Cmax
(μM) | Vss
(L) | Cl
(L/h) | AUC0-∞
(μMh) | Bioavailability
(%) | | Plasma | i.v. | 0.95 | 0.083 | 6.36 | 0.25 | 0.325 | 4.62 | 100 | | Plasma | i.p. | 2.33 | 0.5 | 1.28 | N/A | 0.372 | 1.33 | 28.8 | | Tumor | i.p. | 3.89 | 1 | 8.02 | N/A | 0.06* | 25.8 | N/A | | Plasma | p.o. | 0.57 | 0.5 | 0.432 | N/A | 0.317 | 0.392 | 8.5 |
*Apparent clearance.
| Animal Model: | 6-8 weeks old female CrTacNCr-Fox1nu mice[1] | | Dosage: | 25 mg/kg (U87MG human glioblastoma xenografts) or 40 mg/kg (BT474 human breast cancer xenografts) | | Administration: | i.p. daily for 5 days (U87MG human glioblastoma xenografts); i.p. twice daily for 5 days (BT474 human breast cancer xenografts) | | Result: | 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.
|
| [IC 50]
Akt2: 6 nM (IC50); PKA: 168 nM (IC50); p70S6K: 120 nM (IC50); Autophagy; Apoptosis | [storage]
Store at -20°C | [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. DOI:10.1158/1535-7163.MCT-10-0760
[2] Wang FZ, et al. CCT128930 induces cell cycle arrest, DNA damage, and autophagy independent of Akt inhibition. Biochimie. 2014;103:118-125. DOI:10.1016/j.biochi.2014.04.008 |
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BOC Sciences
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1-631-485-4226; 16314854226 |
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https://www.bocsci.com |
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Ambeed, Inc.
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630-580-1088 |
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www.ambeed.com |
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