Home PI3K/Akt/mTOR PI3K inhibitor - Autophagy activator Idelalisib (CAL-101) For research use only.

Idelalisib (CAL-101)

Synonyms: GS-1101

Idelalisib (CAL-101) is a selective p110δ inhibitor with IC50 of 2.5 nM in cell-free assays; shown to have 40- to 300-fold greater selectivity for p110δ than p110α/β/γ, and 400- to 4000-fold more selectivity to p110δ than C2β, hVPS34, DNA-PK and mTOR. Idelalisib also stimulates autophagy.

Idelalisib (CAL-101) Chemical Structure

Idelalisib (CAL-101) Chemical Structure

CAS No. 870281-82-6

Purity & Quality Control

Idelalisib (CAL-101) Related Products

Signaling Pathway

PI3K Signaling Pathways

PI3K Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description 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
Click to View More Cell Line Experimental Data

Biological Activity

Description Idelalisib (CAL-101) is a selective p110δ inhibitor with IC50 of 2.5 nM in cell-free assays; shown to have 40- to 300-fold greater selectivity for p110δ than p110α/β/γ, and 400- to 4000-fold more selectivity to p110δ than C2β, hVPS34, DNA-PK and mTOR. Idelalisib also stimulates autophagy.
Targets
p110δ [1]
(Cell-free assay)		 p110γ [1]
(Cell-free assay)
2.5 nM 89 nM
In vitro
In vitro

CAL-101 is not sensitive to other PI3K class I subunits including p110α, p110β, and p110γ. CAL-101 specifically blocks FcϵR1 p110δ-mediated CD63 expression with an EC50 of 8 nM in primary basophil. CAL-101 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. CAL-101 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. [1]

CAL-101 induces selective cytotoxicity in CLL cells independent of IgVH mutational status or interphase cytogenetics, primarily through a caspase-dependent mechanism. CAL-101 induces cytotoxicity preferentially to CLL cells compared with normal B cells, without producing cytotoxicity in other hematopoietic cells, compared to LY294002. CAL-101 lacks direct cytotoxic potential to T cells and nature killer (NK) cells. CAL-101 can inhibit production of inflammatory cytokines, such as IL-6, IL-10, TNF-α, and IFN-γ, and activation-induced cytokines, such as CD40L. CAL-101 also antagonizes CD40L-mediated CLL cell survival. [2]

CAL-101 induces an accumulation of cells in G1 and a decrease in the S-phase population in L1236 and L591 cells, which indicates CAL-101 as a novel strategy for the treatment of hodgkin lymphoma (HL). [3]
Kinase Assay PI3K assay
PI3K assay is preformed on whole-cell lysates from CLL or normal B cells. A PI3K ELISA assay is performed. Briefly, whole-cell extracts are added to a mixture of PI(4,5)P2 substrate and reaction buffer containing adenosine triphosphate (ATP) and allowed to incubate at room temperature. The reaction is stopped by adding PI(3,4,5)P3 detector mixed with EDTA (ethylenediaminetetraacetic acid) and allowed to incubate at room temperature for 1 hour. After this time, the mixture is transferred from each well to a PI3K ELISA plate and allowed to incubate 1 hour. Plates are washed and then incubated with secondary detector for 30 minutes. Plates are washed again, and 3,3′,5,5′-tetramethylbenzidine solution is added for 5 minutes at which time H2SO4 is added to stop all reactions. Plates are read at 450 nm on a Labsystems 96-well plate reader.
Cell Research Cell lines CLL B cells or healthy volunteer T cells or NK cells
Concentrations 0.01-100 μM
Incubation Time 48 hours
Method

MTT assays are performed to determine cytotoxicity. 1 × 105 cells are incubated with CAL-101. MTT reagent is then added, and plates are incubated for an additional 20 hours before washing in phosphate-buffered saline. DMSO is added, and absorbance is measured by spectrophotometry at 540 nm in a Labsystems plate reader. Cell viability is also measured at various time points with the use of annexin/PI flow cytometry. Data are analyzed. At least 104 cells are counted for each sample. Results are expressed as the percentage of total positive cells over untreated control. Experiments examining caspase-dependent apoptosis included the addition of 100 μM Z-VAD. Experiments examining survival signals include the addition of 1 μg/mL CD40L, 800 U/mL IL-4, 50 ng/mL BAFF, 20 ng/mL TNF-α, or coculturing on fibronectin or stromal (HS-5 cell line) coated plates. Stromal coculture is done by plating a 75-cm2 flask (80%-100% confluent) per 6-well plate 24 hours before the addition of CLL cells.
Experimental Result Images Methods Biomarkers 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
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date 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 --

Chemical Information & Solubility

Molecular Weight 415.42 Formula

C22H18FN7O
CAS No. 870281-82-6 SDF Download Idelalisib (CAL-101) SDF
Smiles CCC(C1=NC2=C(C(=CC=C2)F)C(=O)N1C3=CC=CC=C3)NC4=NC=NC5=C4NC=N5
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 83 mg/mL ( (199.79 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Frequently Asked Questions

Question 1:
What is the recommended dose of CAL-101 and the route of administration for mouse studies?

Answer:
According to the following paper, S2226 can be used by I.V. administration at the concentration of 40 mg/kg. https://www.ncbi.nlm.nih.gov/pubmed/24625684

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