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CAL-101 (Idelalisib) inhibidor de PI3Kδ

Name: CAL-101 (Idelalisib)
Brand: Selleck Chemicals
SKU: S2226
Rating: 5 (288 reviews)

Cat. No.: S2226

Idelalisib (CAL-101) es un inhibidor selectivo de p110δ con una IC50 de 2,5 nM en ensayos sin células; se ha demostrado que tiene una selectividad de 40 a 300 veces mayor para p110δ que para p110α/β/γ, y de 400 a 4000 veces mayor selectividad para p110δ que para C2β, hVPS34, DNA-PK y mTOR. Idelalisib también estimula la autophagy.

CAL-101 (Idelalisib) PI3K Inhibidor Chemical Structure

Estructura química

Peso molecular: 415.42

Saltar a

Control de calidad (Quality Control)

Lote: Pureza: 99.93%

99.93

Dianas relacionadas	Akt mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Otros PI3K Inhibidores	GDC-0077 (Inavolisib) SAR405 Quercetin (Sophoretin) LY294002 XL147 analogue Tersolisib (STX-478) Buparlisib (BKM120) 740 Y-P (PDGFR 740Y-P) GO-203 TFA Eganelisib (IPI-549)

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Líneas celulares	Tipo de ensayo	Concentración	Tiempo de incubación	Formulación	Descripción de la actividad	PMID
MEC1	Growth Inhibition Assay			DMSO	IC50=20.4 μM	25999352
CLL PBMCs	Growth Inhibition Assay			DMSO	IC50=2.9 nM	25917267
U266	Growth Inhibition Assay	40 μM	48 h		79.5% inhibition rate	25339332
K562	Function Assay	1 μM	3 h		Inhibition of Akt phosphorylation	25014775
K562	Function Assay	1 μM	3 h		Inhibition of P70S6K phosphorylation	25014775
K562	Function Assay	1 μM	3 h		Inhibition of GSK3 phosphorylation	25014775
K562	Growth Inhibition Assay	1 μM	72 h		Inhibition of proliferation	25014775
Primary AML cell	Function Assay	1 μM	3 h		Inhibition of Akt phosphorylation	25014775
Primary AML cell	Function Assay	1 μM	3 h		Inhibition of P70S6K phosphorylation	25014775
Primary AML cell	Function Assay	1 μM	3 h		Inhibition of GSK3 phosphorylation	25014775
Primary AML cell	Growth Inhibition Assay	1 μM	3 h		Suppression of rRNA synthesis	25014775
Microglia	Function Assay	5 μM	10 h	DMSO	Decrease of TNFa secretion from LPS-stimulated p110δD910A/D910A microglia	24625684
Primary CLL cell	Function Assay	1 μM	15 min	DMSO	Blocks BCR-induced LCP1 serine-5 activation	24009233
JEKO-1	Function Assay	1 μM	72 h		Inhibition of Akt phosphorylation in IgM-stimulated JEKO-1	23341541
Granta-519	Function Assay	1 μM	2 h		Inhibition of Akt(t308) phosphorylation	23341541
Granta-519	Function Assay	1 μM	2 h		Inhibition of Akt(s473) phosphorylation	23341541
JEKO-1	Growth Inhibition Assay	10 μM	72 h		Inhibition of proliferation slightly	23341541
JEKO-1	Growth Inhibition Assay	5 μM	72 h		does not induce cell cycle arrest or apoptosis	23676220
MAVER-1	Growth Inhibition Assay	5 μM	72 h		does not induce cell cycle arrest or apoptosis	23676220
MINO	Growth Inhibition Assay	5 μM	72 h		does not induce cell cycle arrest or apoptosis	23676220
SP53	Growth Inhibition Assay	0.1 μM	72 h		does not induce cell cycle arrest or apoptosis	23676220
HH	Growth Inhibition Assay	10 μM	72 h	DMSO	Induction of apoptosis slightly	22801959
Myla	Growth Inhibition Assay	10 μM	72 h	DMSO	does not induce apoptosis	22801959
SR786	Growth Inhibition Assay	10 μM	72 h	DMSO	does not induce apoptosis	22801959
HuT78	Growth Inhibition Assay	10 μM	72 h	DMSO	does not induce apoptosis	22801959
MJ	Growth Inhibition Assay	10 μM	72 h	DMSO	does not induce apoptosis	22801959
DERL7	Growth Inhibition Assay	10 μM	72 h	DMSO	does not induce apoptosis	22801959
L1236	Function Assay	10 μM	2 h		Inhibition of Akt phosphorylation	22210877
L428	Function Assay	10 μM	2 h		Inhibition of Akt phosphorylation	22210877
L591	Function Assay	10 μM	2 h		Inhibition of Akt phosphorylation	22210877
KMH-2	Function Assay	10 μM	2 h		Inhibition of Akt phosphorylation	22210877
L1236	Function Assay	5 μM	24 h		Blocks secretion of the CCL5	22210877
L591	Function Assay	5 μM	24 h		Blocks secretion of the CCL5	22210877
L1236	Apoptosis Assay	5 μM	24 h		Induction of apoptosis	22210877
L591	Apoptosis Assay	5 μM	24 h		Induction of apoptosis	22210877
U-87MG	Function Assay	100 nM	24 h	DMSO	Inhibition of cell migration	22079609
SW1783	Function Assay	100 nM	24 h	DMSO	Inhibition of cell migration	22079609
U-87MG	Function Assay	5 μM	24 h	DMSO	Inhibition of Akt phosphorylation substantially	22079609
SW1783	Function Assay	5 μM	24 h	DMSO	Inhibition of Akt phosphorylation substantially	22079609
U-373MG	Function Assay	5 μM	24 h	DMSO	Inhibition of Akt phosphorylation substantially	22079609
SK-MG3	Function Assay	5 μM	24 h	DMSO	Inhibition of Akt phosphorylation substantially	22079609
SU-DHL-5	Function Assay	1 μM	24 h	DMSO	Induction of apoptosis	20959606
WSU-NHL	Function Assay	1 μM	24 h	DMSO	Induction of apoptosis	20959606
CCRF-SB	Function Assay	1 μM	24 h	DMSO	Induction of apoptosis	20959606
INA-6	Function Assay	5 μM	6 h		Inhibition of PI3K/Akt and ERK pathway	20505158
LB	Function Assay	5 μM	6 h		Inhibition of PI4K/Akt and ERK pathway	20505158
B-cells	Function assay				Inhibition of PI3Kdelta in B-cells by proliferation assay, IC50 = 0.0061 μM.	22924688
MOLM14	Antiproliferative assay		3 days		Antiproliferative activity against human MOLM14 cells after 3 days by CellTiter-Glo assay, IC50 = 3.6 μM.	27774127
MV4-11	Antiproliferative assay		3 days		Antiproliferative activity against human MV4-11 cells after 3 days by CellTiter-Glo assay, IC50 = 6.3 μM.	27774127
Jurkat	Antiproliferative assay		3 days		Antiproliferative activity against human Jurkat cells after 3 days by CellTiter-Glo assay, IC50 = 7.9 μM.	27774127
Loucy	Antiproliferative assay		3 days		Antiproliferative activity against human Loucy cells after 3 days by CellTiter-Glo assay, IC50 = 8.4 μM.	27774127
MOLT4	Antiproliferative assay		3 days		Antiproliferative activity against human MOLT4 cells after 3 days by CellTiter-Glo assay, IC50 = 10.6 μM.	27774127
insect cells	Function assay				Inhibition of recombinant human full length His-tagged PI3Kgamma expressed in insect cells, IC50 = 0.089 μM.	27846451
SUDHL6	Antiproliferative assay		72 hrs		Antiproliferative activity against human SUDHL6 cells measured after 72 hrs by alamar blue assay, IC50 = 0.1176 μM.	27846451
insect cells	Function assay				Inhibition of recombinant human full length His-tagged PI3Kbeta expressed in insect cells, IC50 = 0.565 μM.	27846451
SU-DHL4	Antiproliferative assay		72 hrs		Antiproliferative activity against human SU-DHL4 cells measured after 72 hrs by alamar blue assay, IC50 = 1.6 μM.	27846451
Pfeiffer	Antiproliferative assay		72 hrs		Antiproliferative activity against human Pfeiffer cells measured after 72 hrs by alamar blue assay, IC50 = 6.8 μM.	27846451
KARPAS422	Antiproliferative assay		72 hrs		Antiproliferative activity against human KARPAS422 cells measured after 72 hrs by alamar blue assay, IC50 = 8.1 μM.	27846451
Sf21	Function assay		30 mins		Inhibition of N-terminal His6-tagged recombinant full-length human PI3K p110beta/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2/ATP as substrate after 30 mins by TR-FRET assay, IC50 = 3.7 μM.	28106991
Sf21	Function assay		30 mins		Inhibition of N-terminal His6-tagged recombinant full-length human PI3K p110beta/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2/ATP as substrate after 30 mins by TR-FRET assay, IC50 = 3.7 μM.	28106991
RPMI8266	Antiproliferative assay		72 hrs		Antiproliferative activity against human RPMI8266 cells after 72 hrs by MTT assay, IC50 = 0.00549 μM.	28325601
Raji	Antiproliferative assay		72 hrs		Antiproliferative activity against human Raji cells after 72 hrs by MTT assay, IC50 = 0.00995 μM.	28325601
KARPAS422	Growth inhibition assay				Growth inhibition of human KARPAS422 cells by CCK8 assay, GI50 = 0.68 μM.	28835805
Pfeiffer	Growth inhibition assay				Growth inhibition of human Pfeiffer cells by CCK8 assay, GI50 = 0.74 μM.	28835805
Saos-2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
SK-N-SH	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
MG 63 (6-TG R)	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
NB1643	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
OHS-50	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
Rh41	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
SK-N-MC	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
SUDHL6	Antiproliferative assay		72 hrs		Antiproliferative activity against human SUDHL6 cells after 72 hrs by CCK8 assay, IC50 = 0.65 μM.	29534936
RPMI8226	Antiproliferative assay		72 hrs		Antiproliferative activity against human RPMI8226 cells after 72 hrs by MTT assay, IC50 = 5.49 μM.	29534936
Raji	Antiproliferative assay		72 hrs		Antiproliferative activity against human Raji cells after 72 hrs by MTT assay, IC50 = 9.95 μM.	29534936
SU-DHL6	Growth inhibition assay				Growth inhibition of human SU-DHL6 cells by CellTiter-Glo assay, GI50 = 0.042 μM.	29601991
MOLM13	Growth inhibition assay		72 hrs		Growth inhibition of human MOLM13 cells after 72 hrs by CellTiter-Glo luminescent assay, GI50 = 1.7 μM.	30053721
MOLM14	Growth inhibition assay		72 hrs		Growth inhibition of human MOLM14 cells after 72 hrs by CellTiter-Glo luminescent assay, GI50 = 6.4 μM.	30053721
MOLM14	Antitumor assay	100 mg/kg	14 days		Antitumor activity against human MOLM14 cells xenografted in nu/nu mouse assessed as tumor growth inhibition at 100 mg/kg, po administered daily via gavage dosed for 14 days and measured daily during compound dosing relative to control	30053721
MOLM14	Antitumor assay	100 mg/kg	14 days		Antitumor activity against human MOLM14 cells xenografted in nu/nu mouse assessed as induction of apoptosis at 100 mg/kg, po administered daily via gavage dosed for 14 days and measured daily during compound dosing by TUNEL based assay	30053721
MOLM14	Antitumor assay	100 mg/kg	14 days		Antitumor activity against human MOLM14 cells xenografted in nu/nu mouse assessed as inhibition of tumor proliferation 100 mg/kg, po administered daily via gavage dosed for 14 days and measured daily during compound dosing by Ki-67 labelling based immunoh	30053721
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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	415.42	Fórmula	C₂₂H₁₈FN₇O	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	870281-82-6	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	GS-1101			Smiles	CCC(C1=NC2=C(C(=CC=C2)F)C(=O)N1C3=CC=CC=C3)NC4=NC=NC5=C4NC=N5

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 83 mg/mL (199.79 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Water : Insoluble

Ethanol : Insoluble

Calculadora de Molaridad

Masa	Concentración	Volumen	Peso molecular
=	×	×

Calculadora de Dilución Calculadora de Peso Molecular

In vivo Lote:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

Dosis: mg/kg Peso promedio de los animales: g Volumen de dosificación por animal:μL Número de animales:

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH₂O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción (Mechanism of Action)

Targets/IC₅₀/Ki	p110δ (Cell-free assay) 2.5 nM p110γ (Cell-free assay) 89 nM
In vitro	Idelalisib (CAL-101) no es sensible a otras subunidades de la clase I de PI3K, incluyendo p110α, p110β y p110γ. Bloquea específicamente la expresión de CD63 mediada por FcϵR1 p110δ con una EC50 de 8 nM en basófilos primarios. Este compuesto exhibe una mayor actividad en células de leucemia linfoblástica aguda de células B (B-ALL) y leucemia linfocítica crónica (CLL) en comparación con células de leucemia mieloide aguda (AML) y neoplasia mieloproliferativa (MPN). Produce la reducción de pAktS473, pAktT308 y el objetivo corriente abajo S6 en células SU-DHL-5, KARPAS-422 y CCRF-SB con una EC50 de 0,1 a 1,0 μM. Induce citotoxicidad selectiva en células de CLL independientemente del estado mutacional de IgVH o la citogenética de interfase, principalmente a través de un mecanismo dependiente de caspasas. El compuesto induce citotoxicidad preferentemente en células de CLL en comparación con linfocitos B normales, sin producir citotoxicidad en otras células hematopoyéticas, en comparación con LY294002. Carece de potencial citotóxico directo sobre células T y células asesinas naturales (NK). Puede inhibir la producción de citocinas inflamatorias, como IL-6, IL-10, TNF-α e IFN-γ, y citocinas inducidas por la activación, como CD40L. También antagoniza la supervivencia de células de CLL mediada por CD40L. Induce una acumulación de células en G1 y una disminución en la población de fase S en células L1236 y L591, lo que indica que este compuesto es una nueva estrategia para el tratamiento del linfoma de Hodgkin (HL).
Ensayo de quinasa	Ensayo de PI3K
Ensayo de quinasa	El ensayo de PI3K se realiza en lisados de células enteras de CLL o linfocitos B normales. Se realiza un ensayo ELISA de PI3K. Brevemente, los extractos de células enteras se añaden a una mezcla de sustrato de PI(4,5)P2 y tampón de reacción que contiene adenosina trifosfato (ATP) y se incuban a temperatura ambiente. La reacción se detiene añadiendo detector de PI(3,4,5)P3 mezclado con EDTA (ácido etilendiaminotetraacético) y se incuba a temperatura ambiente durante 1 hora. Después de este tiempo, la mezcla se transfiere de cada pocillo a una placa ELISA de PI3K y se incuba durante 1 hora. Las placas se lavan y luego se incuban con un detector secundario durante 30 minutos. Las placas se lavan de nuevo, y se añade una solución de 3,3′,5,5′-tetrametilbencidina durante 5 minutos, momento en el que se añade H2SO4 para detener todas las reacciones. Las placas se leen a 450 nm en un lector de placas de 96 pocillos de Labsystems.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/20959606/ [2] https://pubmed.ncbi.nlm.nih.gov/20522708/ [3] https://pubmed.ncbi.nlm.nih.gov/22210877/ [4] https://pubmed.ncbi.nlm.nih.gov/24625684/

Aplicaciones (Applications)

Métodos	Biomarcadores	Imágenes	PMID
Western blot	PUMA / p53 Bim / Bcl-xl / Bid / Mcl-1 p-p65 p-AKT / AKT Cleaved caspase 3 / Cleaved caspase 9 Mcl-1 / Bcl-2 / Bid / Bcl-xl / Noxa / Bak / Bax p-FoxO3a / FoxO3a Akt(T308) / PDK1(S241) / GSK-3β(S9)		28008149
Growth inhibition assay	Cell viability Cell viability		28008149

Información del ensayo clínico (Clinical Trial Information)

(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
NCT03582098	Completed	Chronic Lymphocytic Leukaemia	Gilead Sciences	September 12 2018	--
NCT03151057	Terminated	B Cells-Tumors\|B Cell Chronic Lymphocytic Leukemia\|Follicular Lymphoma\|Mantle Cell Lymphoma\|Large B-Cell Diffuse Lymphoma of Bone (Diagnosis)	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins\|Gilead Sciences	July 31 2018	Phase 1
NCT03568929	Completed	Follicular Non-Hodgkin''s Lymphoma Refractory	Gilead Sciences	May 25 2018	--

Preguntas frecuentes (Frequently Asked Questions)

Pregunta 1:
What is the recommended dose and the route of administration for it in mouse studies?

Respuesta:
According to the following paper, it can be used by I.V. administration at the concentration of 40 mg/kg. https://www.ncbi.nlm.nih.gov/pubmed/24625684

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):