Idelalisib (CAL-101, GS-1101)

Catalog No.S2226

Idelalisib (CAL-101, GS-1101) Chemical Structure

Molecular Weight(MW): 415.42

Idelalisib (CAL-101, GS-1101) 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.

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Cited by 38 Publications

5 Customer Reviews

  • Invasive migration of RA FLS was analyzed through growth factor–reduced Matrigel-coated transwell inserts in the presence or absence of 1 µM INK007, 5 µM CAL-101, or 0.3 µM IPI-145, or 0.3 µM GDC-0941 inhibitors or DMSO. Cells were allowed to invade through Matrigel toward PDGF-BB (25 ng/ml) containing media for 24 h and were fixed and stained with Hemacolor staining kit.

    J Immunol, 2014, 192(5): 2063-70 . Idelalisib (CAL-101, GS-1101) purchased from Selleck.

    Ppp2r1afl/fl BCR-ABL1 B-ALL cells transduced with 4-OHT-inducible Cre-ERT2 (Cre) or ERT2-vector (EV) were treated with 4-OHT for 3 days and cell lysates were studied by phospho-protein array analysis. Ppp2r1afl/fl BCR-ABL1 ALL cells were transduced with 4-OHT-inducible Cre or EV control and incubated in the presence of the small molecule signaling inhibitor idelalisib (32 μmol/L; C). Percentages of GFP+ cells were measured by flow cytometry at the times indicated following 4-OHT-treatment. Data are shown as mean ± standard deviation (SD) and representative of at least three independent experiments.

    Cell, 2018, 173(2):470-484. Idelalisib (CAL-101, GS-1101) purchased from Selleck.

  • 293T cells were transfected with HA-tagged Fbxo45. At 48 h after transfection, cells were treated with AKT inhibitor (CAL-101; 10 uM, 4 h), cell extracts from the cytoplasm or nuclei were subjected to IP with anti-HA resin followed by western blot analysis with indicated antibodies.

    Cell Death Differ 2014 21(10), 1535-45. Idelalisib (CAL-101, GS-1101) purchased from Selleck.

    Isoform-selective PI3K inhibitors blocked PI3K signaling in corresponding Rh30-Myr-p110 cells. Rh30-Myr-p110s cells were cultured in serum-free medium for 12 h, and then exposed to CAL-101 at indicated concentrations for additional 1 h. The cells were collected to detect the level of phosphorylated and total Akt. β-Actin was served as loading control.

    Acta Pharmacol Sin 2013 34(9),1201-7. Idelalisib (CAL-101, GS-1101) purchased from Selleck.

  • After starved in serum-free medium for 24 h,A549 cells incubated with the indicated concentrations of CAL-101 for 3 h,followed by 20-minute stimolation of 100ng/ml EGF.

    Dr. Zhang of Tianjin Medical University. Idelalisib (CAL-101, GS-1101) purchased from Selleck.

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Biological Activity

Description Idelalisib (CAL-101, GS-1101) 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.
Targets
p110δ [1]
(Cell-free assay)
p110γ [1]
(Cell-free assay)
2.5 nM 89 nM
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MEC1 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEjVb49FVVOR M2[3fmlEPTB;MkCuOEDPxE1? MWmyOVk6QTN3Mh?=
CLL PBMCs NVPpbFNmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3TaPGROW09? Mk\qTWM2OD1{Lkmgcm0> MmjzNlU6OTd{Nke=
U266 NW\4W2tUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1fvUFQxKM7:TR?= MXK0PEBp MlPzO|kvPSViaX7obYJqfGmxbjDyZZRm NFXXelgzPTN|OUOzNi=>
K562 MkXLSpVv[3Srb36gRZN{[Xl? MlXhNUDPxE1? NGDsfWM{KGh? M1m0T2lvcGmkaYTpc44hd2ZiQXv0JJBpd3OyaH;yfYxifGmxbh?= NF3oO4ozPTBzNEe3OS=>
K562 NIjzbXlHfW6ldHnvckBCe3OjeR?= NWPDcFJbOSEQvF2= NIfzU3k{KGh? NXPwXlVDUW6qaXLpeIlwdiCxZjDQO|BUPkticHjvd5Bpd3K7bHH0bY9v MkjuNlUxOTR5N{W=
K562 M2jmT2Z2dmO2aX;uJGF{e2G7 NWGyNVQyOSEQvF2= NULvUVIzOyCq MknXTY5pcWKrdHnvckBw\iCJU1uzJJBpd3OyaH;yfYxifGmxbh?= MkfONlUxOTR5N{W=
K562 NESwVYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHPUXZgyKM7:TR?= MVi3NkBp MVHJcohq[mm2aX;uJI9nKHC{b3zp[oVz[XSrb36= M4Prb|I2ODF2N{e1
Primary AML cell MmrHSpVv[3Srb36gRZN{[Xl? MnzHNUDPxE1? MlvzN{Bp NYnKXW1FUW6qaXLpeIlwdiCxZjDBb5QheGixc4Doc5J6dGG2aX;u M1j3T|I2ODF2N{e1
Primary AML cell MlzhSpVv[3Srb36gRZN{[Xl? MUOxJO69VQ>? NGjkdGs{KGh? MnPYTY5pcWKrdHnvckBw\iCSN{DTOmsheGixc4Doc5J6dGG2aX;u MYWyOVAyPDd5NR?=
Primary AML cell NHu3UpNHfW6ldHnvckBCe3OjeR?= NYK1TINIOSEQvF2= M1LaNVMhcA>? MnjHTY5pcWKrdHnvckBw\iCJU1uzJJBpd3OyaH;yfYxifGmxbh?= NFy0XIMzPTBzNEe3OS=>
Primary AML cell MoTlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUCxJO69VQ>? MlTWN{Bp NV70PXAyW3WycILld5Nqd25ib3[gdnJPSSC|eX70bIV{cXN? MUeyOVAyPDd5NR?=
Microglia M1\remZ2dmO2aX;uJGF{e2G7 M2LNc|Uh|ryP M{\oWFExKGh? MX7EUXNQ MXTE[YNz\WG|ZTDv[kBVVk[jIIPlZ5JmfGmxbjDmdo9uKEySUz3zeIlufWyjdHXkJEBxOTFyzsTEPVExSS:GOUGwRUBucWO{b3fsbYE> M37DSFI1PjJ3Nki0
Primary CLL cell NHPER4dHfW6ldHnvckBCe3OjeR?= NFz3NIgyKM7:TR?= MWexOUBucW5? M4PyRWROW09? Mkf3Roxw[2u|IFLDVk1qdmS3Y3XkJGxEWDFic3XybY5mNTViYXP0bZZifGmxbh?= M{e3RVI1ODB7MkOz
JEKO-1 M2rYdmZ2dmO2aX;uJGF{e2G7 NFOwcYYyKM7:TR?= M{TqOVczKGh? MWXJcohq[mm2aX;uJI9nKEGtdDDwbI9{eGixconsZZRqd25iaX6gTYdONXO2aX31cIF1\WRiSlXLU{0y Mn7zNlM{PDF3NEG=
Granta-519 Mli2SpVv[3Srb36gRZN{[Xl? MkHsNUDPxE1? MVuyJIg> M1i2dWlvcGmkaYTpc44hd2ZiQXv0LJQ{ODhrIIDoc5NxcG:{eXzheIlwdg>? NYfBd|hTOjN|NEG1OFE>
Granta-519 MXrGeY5kfGmxbjDBd5NigQ>? M4rORlEh|ryP MlTnNkBp MlX3TY5pcWKrdHnvckBw\iCDa4Sod|Q4OylicHjvd5Bpd3K7bHH0bY9v MVKyN|M1OTV2MR?=
JEKO-1 MoDIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MofTNVAh|ryP M3jzOFczKGh? NW\Nb2oyUW6qaXLpeIlwdiCxZjDwdo9tcW[ncnH0bY9vKHOuaXfoeIx6 Mon5NlM{PDF3NEG=
JEKO-1 MnLqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlnuOUDPxE1? MV:3NkBp NX\TT5ZH\G:nczDuc5QhcW6mdXPlJINmdGxiY4njcIUh[XK{ZYP0JI9zKGGyb4D0c5Nqew>? NVrDRYQ3OjN4N{[yNlA>
MAVER-1 NGP6eHFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4fuelUh|ryP MmnTO|IhcA>? NFTWWFZld2W|IH7veEBqdmS3Y3WgZ4VtdCCleXPs[UBienKnc4Sgc5Ih[XCxcITvd4l{ MVqyN|Y4PjJ{MB?=
MINO MnziS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mlz5OUDPxE1? MVK3NkBp MmX3[I9meyCwb4SgbY5lfWOnIHPlcIwh[3mlbHWgZZJz\XO2IH;yJIFxd3C2b4Ppdy=> NHrOUFEzOzZ5NkKyNC=>
SP53 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXiwMlEh|ryP MkTCO|IhcA>? M163VYRw\XNibn;0JIlv\HWlZTDj[YxtKGO7Y3zlJIFzemW|dDDvdkBieG:ydH;zbZM> NWP2XFBPOjN4N{[yNlA>
HH MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXzvVFFEOTBizszN MoW3O|IhcA>? NWLhfJNiTE2VTx?= NYD3eYlqUW6mdXP0bY9vKG:oIHHwc5B1d3OrczDzcIlocHSueR?= M3zZcVIzQDBzOUW5
Myla NX76ZpVTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVjGfodDOTBizszN MkfRO|IhcA>? MVnEUXNQ M3:4RYRw\XNibn;0JIlv\HWlZTDhdI9xfG:|aYO= MYmyNlgxOTl3OR?=
SR786 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4W5SFExKM7:TR?= M{jsS|czKGh? Mn3sSG1UVw>? M3fjeoRw\XNibn;0JIlv\HWlZTDhdI9xfG:|aYO= MmnXNlI5ODF7NUm=
HuT78 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXixNEDPxE1? NFHkZmg4OiCq NG\UcIRFVVOR NXKyTW5m\G:nczDuc5QhcW6mdXPlJIFxd3C2b4Ppdy=> M1f3bFIzQDBzOUW5
MJ NF3ZS3pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkToNVAh|ryP M2\TXVczKGh? M1jx[GROW09? NF30[5Zld2W|IH7veEBqdmS3Y3WgZZBweHSxc3nz MnroNlI5ODF7NUm=
DERL7 NFjuU5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkeyNVAh|ryP NWG3UVQ{PzJiaB?= MkHnSG1UVw>? NFLw[m1ld2W|IH7veEBqdmS3Y3WgZZBweHSxc3nz NY\FT45[OjJ6MEG5OVk>
L1236 NFjLb3JHfW6ldHnvckBCe3OjeR?= MlfDNVAh|ryP NHnTbZQzKGh? NWO5VpBqUW6qaXLpeIlwdiCxZjDBb5QheGixc4Doc5J6dGG2aX;u MoeyNlIzOTB6N{e=
L428 MmPoSpVv[3Srb36gRZN{[Xl? M3TaOFExKM7:TR?= MoPMNkBp NFnzeHZKdmirYnn0bY9vKG:oIFHreEBxcG:|cHjvdplt[XSrb36= NU\4TlJJOjJ{MUC4O|c>
L591 NVrsb2xYTnWwY4Tpc44hSXO|YYm= MWixNEDPxE1? MXeyJIg> MnXnTY5pcWKrdHnvckBw\iCDa4SgdIhwe3Cqb4L5cIF1cW:w NVvSWG5EOjJ{MUC4O|c>
KMH-2 NYTw[mp1TnWwY4Tpc44hSXO|YYm= MVOxNEDPxE1? NYHNfpNpOiCq M3PnN2lvcGmkaYTpc44hd2ZiQXv0JJBpd3OyaH;yfYxifGmxbh?= NE[2bFMzOjJzMEi3Oy=>
L1236 NHTJUItHfW6ldHnvckBCe3OjeR?= MkjOOUDPxE1? MkjENlQhcA>? M2ftWmJtd2OtczDz[YNz\XSrb36gc4YhfGinIFPDUFU> NXLhRVhtOjJ{MUC4O|c>
L591 MlHqSpVv[3Srb36gRZN{[Xl? NH:5O2Y2KM7:TR?= MVqyOEBp NY\p[|hCSmyxY3vzJJNm[3KndHnvckBw\iC2aHWgR2NNPQ>? MYGyNlIyODh5Nx?=
L1236 MUHBdI9xfG:|aYOgRZN{[Xl? M4HoSVUh|ryP Mk[xNlQhcA>? MWHJcoR2[3Srb36gc4Yh[XCxcITvd4l{ M4fnUVIzOjFyOEe3
L591 NVLZZplwSXCxcITvd4l{KEG|c3H5 MW[1JO69VQ>? MUmyOEBp MX3JcoR2[3Srb36gc4Yh[XCxcITvd4l{ NFqxWJgzOjJzMEi3Oy=>
U-87MG M3mxbGZ2dmO2aX;uJGF{e2G7 NWO4SXFxOTByIH7N NGfWOIwzPCCq M3\WW2ROW09? NEC4XGtKdmirYnn0bY9vKG:oIDDj[YxtKG2rZ4LheIlwdg>? NX3nRm1lOjJyN{m2NFk>
SW1783 NYDySpJ3TnWwY4Tpc44hSXO|YYm= NYnsbZZ3OTByIH7N M1LXSFI1KGh? MXzEUXNQ MX7Jcohq[mm2aX;uJI9nKCClZXzsJI1q\3KjdHnvci=> NYjFXJZDOjJyN{m2NFk>
U-87MG MV3GeY5kfGmxbjDBd5NigQ>? M1;mO|Uh|ryP NHjnS2wzPCCq M{jqTGROW09? Ml75TY5pcWKrdHnvckBw\iCDa4SgdIhwe3Cqb4L5cIF1cW:wIIP1ZpN1[W62aXHscJk> NHnFVYozOjB5OU[wPS=>
SW1783 MknCSpVv[3Srb36gRZN{[Xl? NYXxbIJDPSEQvF2= NYPTVJpuOjRiaB?= MW\EUXNQ MX3Jcohq[mm2aX;uJI9nKEGtdDDwbI9{eGixconsZZRqd25ic4Xid5RidnSrYXzsfS=> Mk\kNlIxPzl4MEm=
U-373MG MmjuSpVv[3Srb36gRZN{[Xl? M33yVFUh|ryP M3TaVFI1KGh? MYHEUXNQ MUDJcohq[mm2aX;uJI9nKEGtdDDwbI9{eGixconsZZRqd25ic4Xid5RidnSrYXzsfS=> MYqyNlA4QTZyOR?=
SK-MG3 NVPKfG5rTnWwY4Tpc44hSXO|YYm= MnjCOUDPxE1? MkmxNlQhcA>? MVTEUXNQ NHznUWhKdmirYnn0bY9vKG:oIFHreEBxcG:|cHjvdplt[XSrb36gd5Vje3SjboTpZYxtgQ>? NXrHNJAxOjJyN{m2NFk>
SU-DHL-5 NUHRZWZETnWwY4Tpc44hSXO|YYm= MoLwNUDPxE1? NXW0bFkzOjRiaB?= NHLpdYlFVVOR MVjJcoR2[3Srb36gc4Yh[XCxcITvd4l{ NEfJUpUzODl3OU[wOi=>
WSU-NHL MXvGeY5kfGmxbjDBd5NigQ>? NYHveJMyOSEQvF2= NH\hfXgzPCCq M2nsT2ROW09? M1zzNmlv\HWldHnvckBw\iCjcH;weI9{cXN? NFqyS44zODl3OU[wOi=>
CCRF-SB MVjGeY5kfGmxbjDBd5NigQ>? NW\ne|luOSEQvF2= NEG0Z3gzPCCq NGfkRXBFVVOR NVW2SXV{UW6mdXP0bY9vKG:oIHHwc5B1d3Orcx?= NYLaVY9ZOjB7NUm2NFY>
INA-6 NXHVeolETnWwY4Tpc44hSXO|YYm= NFT5dZU2KM7:TR?= NUHSOo9PPiCq MWTJcohq[mm2aX;uJI9nKFCLM1uvRYt1KGGwZDDFVmsheGG2aIfhfS=> NX;NdI56OjB3MEWxOVg>
LB MXLGeY5kfGmxbjDBd5NigQ>? NFi0VVA2KM7:TR?= MWO2JIg> MmLpTY5pcWKrdHnvckBw\iCSSUTLM2FsfCCjbnSgSXJMKHCjdHj3ZZk> MnjHNlA2ODVzNUi=

... Click to View More Cell Line Experimental Data

Protocol

Kinase Assay:[2]
+ Expand

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:[2]
+ Expand
  • 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 with protamine sulfate 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.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 83 mg/mL warmed (199.79 mM)
Ethanol 23 mg/mL (55.36 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
30% PEG 400 (dissolve first)+0.5% Tween 80+5% Propylene glycol
For best results, use promptly after mixing.
30mg/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.

Chemical Information

Molecular Weight 415.42
Formula

C22H18FN7O

CAS No. 870281-82-6
Storage powder
in solvent
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03349346 Recruiting Diffuse Large B-Cell Lymphoma|Mediastinal B-cell Lymphoma Gilead Sciences June 2019 Phase 1
NCT03639324 Not yet recruiting Chronic Lymphocytic Leukemia|CLL|Relapsed CLL|Refractory Chronic Lymphocytic Leukemia|Relapsed Chronic Lymphocytic Leukemia Virginia Commonwealth University January 31 2019 Phase 1
NCT03545035 Not yet recruiting Chronic Lymphocytic Leukemia Gruppo Italiano Malattie EMatologiche dell''Adulto|ERIC Group December 2018 --
NCT03582098 Recruiting Chronic Lymphocytic Leukaemia Gilead Sciences September 12 2018 --
NCT03742323 Recruiting Acute Lymphoblastic Leukemia PETHEMA Foundation July 1 2018 Phase 1|Phase 2
NCT03151057 Recruiting 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

Tech Support

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.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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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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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID