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CAL-101 (Idelalisib) inhibiteur de PI3Kδ

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

Réf. Catalogue: S2226

Idelalisib (CAL-101) est un inhibiteur sélectif de la p110δ avec une IC50 de 2,5 nM dans les essais sans cellules ; il a été démontré qu'il a une sélectivité de 40 à 300 fois supérieure pour la p110δ que pour la p110α/β/γ, et une sélectivité de 400 à 4000 fois supérieure pour la p110δ que pour la C2β, hVPS34, DNA-PK et mTOR. Idelalisib stimule également l'autophagie.

CAL-101 (Idelalisib) PI3K Inhibiteur Chemical Structure

Structure chimique

Poids moléculaire: 415.42

Aller à

Contrôle Qualité (Quality Control)

Lot : Pureté : 99.93%

99.93

Cibles apparentées	Akt mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Autre PI3K Inhibiteurs	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)

Culture cellulaire, traitement et concentration de travail
(Cell Culture, Treatment & Working Concentration)

Lignées cellulaires	Type d'essai	Concentration	Temps d'incubation	Formulation	Description de l'activité	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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Informations chimiques, stockage et stabilité (Chemical Information, Storage & Stability)

Poids moléculaire	415.42	Formule	C₂₂H₁₈FN₇O	Stockage (À compter de la date de réception)	3 ans-20°Cpoudre
N° CAS	870281-82-6	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	GS-1101			Smiles	CCC(C1=NC2=C(C(=CC=C2)F)C(=O)N1C3=CC=CC=C3)NC4=NC=NC5=C4NC=N5

Solubilité (Solubility)

In vitro
Lot:

DMSO : 83 mg/mL (199.79 mM)
(Le DMSO contaminé par l'humidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Water : Insoluble

Ethanol : Insoluble

Calculateur de molarité

Masse	Concentration	Volume	Poids moléculaire
=	×	×

Calculateur de dilution Calculateur de poids moléculaire

In vivo Lot:
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.

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Saisir les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant l'expérience)

Dosage : mg/kg Poids moyen des animaux : g Volume de dosage par animal :μL Nombre d'animaux :

Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter d'abord s'il n'y a pas de formulation in vivo dans la section Solubilité.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Résultats du calcul :

Concentration de travail : mg/ml;

Méthode de préparation du liquide maître DMSO : mg médicament prédissous dans μL DMSO ( Concentration du liquide maître mg/mL, Veuillez nous contacter d'abord si la concentration dépasse la solubilité du DMSO du lot de médicament. )

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouterμL PEG300, mélanger et clarifier, puis ajouterμL Tween 80, mélanger et clarifier, puis ajouter μL ddH₂O, mélanger et clarifier.

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouter μL Huile de maïs, mélanger et clarifier.

Note : 1. Veuillez vous assurer que le liquide est clair avant d'ajouter le solvant suivant.
2. Assurez-vous d'ajouter le(s) solvant(s) dans l'ordre. Vous devez vous assurer que la solution obtenue, lors de l'ajout précédent, est une solution claire avant de procéder à l'ajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie chaud peuvent être utilisées pour faciliter la dissolution.

Mécanisme d'action (Mechanism of Action)

Targets/IC₅₀/Ki	p110δ (Cell-free assay) 2.5 nM p110γ (Cell-free assay) 89 nM
In vitro	Idelalisib (CAL-101) is not sensitive to other PI3K class I subunits including p110α, p110β, and p110γ. It specifically blocks FcϵR1 p110δ-mediated CD63 expression with an EC50 of 8 nM in primary basophil. This compound exhibits greater activity in B-cell acute lymphoblastic leukemia (B-ALL) and chronic lymphocytic leukemia (CLL) cells compared with acute myeloid leukemia (AML) and myeloproliferative neoplasm (MPN) cells. It produces the reduction in pAktS473, pAktT308, and the downstream target S6 in SU-DHL-5, KARPAS-422 and CCRF-SB cells with EC50 of 0.1 to 1.0 μM. It induces selective cytotoxicity in CLL cells independent of IgVH mutational status or interphase cytogenetics, primarily through a caspase-dependent mechanism. The compound induces cytotoxicity preferentially to CLL cells compared with normal B cells, without producing cytotoxicity in other hematopoietic cells, compared to LY294002. It lacks direct cytotoxic potential to T cells and nature killer (NK) cells. It can inhibit production of inflammatory cytokines, such as IL-6, IL-10, TNF-α, and IFN-γ, and activation-induced cytokines, such as CD40L. It also antagonizes CD40L-mediated CLL cell survival. It induces an accumulation of cells in G1 and a decrease in the S-phase population in L1236 and L591 cells, which indicates this compound as a novel strategy for the treatment of hodgkin lymphoma (HL).
Essai kinase	Essai PI3K
Essai kinase	L'essai PI3K est réalisé sur des lysats de cellules entières de cellules de LLC ou de cellules B normales. Un essai ELISA PI3K est effectué. En bref, des extraits de cellules entières sont ajoutés à un mélange de substrat PI(4,5)P2 et de tampon de réaction contenant de l'adénosine triphosphate (ATP) et sont laissés à incuber à température ambiante. La réaction est arrêtée par l'ajout d'un détecteur de PI(3,4,5)P3 mélangé à de l'EDTA (acide éthylènediaminetétraacétique) et laissée à incuber à température ambiante pendant 1 heure. Après ce temps, le mélange est transféré de chaque puits à une plaque ELISA PI3K et laissé à incuber pendant 1 heure. Les plaques sont lavées puis incubées avec un détecteur secondaire pendant 30 minutes. Les plaques sont lavées à nouveau, et une solution de 3,3′,5,5′-tétraméthylbenzidine est ajoutée pendant 5 minutes, après quoi du H2SO4 est ajouté pour arrêter toutes les réactions. Les plaques sont lues à 450 nm sur un lecteur de plaques 96 puits Labsystems.
Références	[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/

Applications (Applications)

Méthodes	Biomarqueurs	Images	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

Informations sur l'essai clinique (Clinical Trial Information)

(données du https://clinicaltrials.gov, mis à jour le 2024-05-22)

Numéro NCT	Recrutement	Conditions	Promoteur/Collaborateurs	Date de début	Phases
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	--

Foire aux questions (Frequently Asked Questions)

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

Réponse :
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):