CCT128930 885499-61-6

.cp_wz table {border-top: 1px solid #ccc; border-left: 1px solid #ccc; } .cp_wz table td {border-right: 1px solid #ccc; borda inferior: 1px sólido #ccc; preenchimento: 5px 0px 0px 5px;} .cp_wz tabela th {border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; preenchimento: 5px 0px 0px 5px;} \ n Peso molecular: 341,84 CCT128930 é um inibidor potente, competitivo e seletivo de ATP de Akt2 com IC50 de 6 nM, seletividade 28 vezes maior para Akt2 do que a quinase PKA intimamente relacionada. \ n CCT128930 exibe atividade antiproliferativa marcada contra linhas de células tumorais humanas deficientes em PTEN, incluindo células de glioblastoma humano U87MG, células de câncer de próstata humano LNCaP e células de câncer de próstata humano PC3 com GI50 de 6,3 μM, 0,35 μM e 1,9 μM, respectivamente. Além disso, CCT128930 causa uma parada G1 em células de glioblastoma humano U87MG nulas de PTEN e bloqueio da via Akt. CCT128930 a 25 mg / kg ip mostra um efeito antitumoral marcado em xenoenxertos de glioblastoma humano U87MG nulo para PTEN com uma relação tratado: controle (T / C) de 48% no dia 12. Em HER2 positivo, mama humana BT474 mutante PIK3CA xenoenxertos de câncer, CCT128930 a 40 mg / kg também produz um efeito antitumoral profundo com parada de crescimento completa e uma razão T / C de 29% no dia 22. CCT128930 administrado por via intravenosa atinge um pico de concentração de 6,4 μM no plasma e é eliminado com um meia-vida relativamente curta, alto volume de distribuição e depuração rápida, dando uma área sob a curva AUC0-∞ de 4,6 μM h. O CCT128930 administrado via ip leva à concentração de droga no plasma de pico de 1,3 μM e a AUC0-∞ correspondente de 1,3 μM · h. A administração oral de CCT128930 leva ao pico de concentração plasmática de apenas 0,43 μM e a uma AUC0-∞ correspondentemente baixa de 0,4 μM · h. \ n

Kinase assays	Profiling against 50 different human kinases is carried out using 10 μM CCT128930 at an ATP concentration equivalent to the Km for each enzyme.

Ensaio de células: [1]

Cell lines	U87MG, LNCaP and PC3 cells
Concentrations	0-18.9 μM
Incubation Time	48 hours
Method	Cells are seeded in 96-well plates and allowed to attach for 36 hours to ensure exponential growth prior to treatment. In vitro antiproliferative activity is determined using a 96-hour SRB assay. TCA-fixed cells are stained for 30 minutes with 0.4% (wt/vol) SRB dissolved in 1% acetic acid. At the end of the staining period, SRB is removed and cultures are quickly rinsed four times with 1% acetic acid to remove unbound dye. The acetic acid is poured directly into the culture wells from a beaker. This procedure permits rinsing to be performed quickly so that desorption of protein-bound dye does not occur. Residual wash solution is removed by sharply flicking plates over a sink, which ensures the complete removal of rinsing solution. Because of the strong capillary action in 96-well plates, draining by gravity alone often fails to remove the rinse solution when plates are simply inverted. After being rinsed, the cultures are air dried until no standing moisture is visible. Bound dye is solubilized with 10 mM unbuffered Tris base (pH 10.5) for 5 minutes on a gyratory shaker. OD is read in either a UVmax microtiter plate reader or a Beckman DU-70 spectrophotometer. For maximum sensitivity, OD is measured at 564 nm. Because readings are linear with dye concentrations only below 1.8 OD units, however, suboptimal wavelengths are generally used, so that all samples in an experiment remains within the linear OD range. With most cell lines, wavelengths of approximately 490-530 nm works well for this purpose.

Estudo Animal: [1]

Animal Models	PTEN-null U87MG human glioblastoma cells are injected subcutaneously (s.c.) in the right flank of female CrTacNCr-Fox1nu mice. For HER2-positive, PIK3CA-mutant BT474 human breast cancer xenografts, cells are administered s.c. in medium supplemented with M
Formulation	CCT128930 is dissolved in 10% DMSO, 5% Tween 20, and 85% saline.
Dosages	≤50 mg/kg
Administration	Administered via i.p.
Solubility	1% DMSO/30% polyethylene glycol/1% Tween 80, 11 mg/mL
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Conversão de diferentes modelos de animais com base em BSA (valor com base em dados das diretrizes preliminares da FDA)

Species	Baboon	Dog	Monkey	Rabbit	Guinea pig	Rat	Hamster	Mouse
Weight (kg)	12	10	3	1.8	0.4	0.15	0.08	0.02
Body Surface Area (m2)	0.6	0.5	0.24	0.15	0.05	0.025	0.02	0.007
Km factor	20	20	12	12	8	6	5	3

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

Por exemplo, para modificar a dose de resveratrol usada para um camundongo (22,4 mg / kg) para uma dose baseada na BSA para um rato, multiplique 22,4 mg / kg pelo fator Km para um camundongo e, em seguida, divida pelo fator Km para um rato. Este cálculo resulta em uma dose equivalente de rato para o resveratrol de 11,2 mg / kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×	mouse Km(3)	= 11.2 mg/kg
	rat Km(6)

\ n Informação Química

Molecular Weight (MW)	341.84
Formula	C18H20ClN5
CAS No.	885499-61-6

Storage	3 years -20℃Powder
	6 months-80℃in solvent (DMSO, water, etc.)
Synonyms

Solubility (25°C) *	In vitro	DMSO	68 mg/mL (198.92 mM)
		Water	<1 mg/mL (
		Ethanol	6 mg/mL (17.55 mM)
	In vivo	1% DMSO/30% polyethylene glycol/1% Tween 80	11 mg/mL
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Name	4-(4-chlorobenzyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-amine

Calculadora de molaridade Calculadora de diluição Calculadora de peso molecular

Grupo de Produto : PI3K / Akt / mTOR > Inibidor de Akt