Idelalisib (CAL-101, GS-1101)

For research use only.

Catalog No.S2226

143 publications

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. Idelalisib also stimulates autophagy.

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Selleck's Idelalisib (CAL-101, GS-1101) has been cited by 143 publications

Purity & Quality Control

Choose Selective PI3K Inhibitors

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. Idelalisib also stimulates autophagy.
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 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXK0fWp2TE2VTx?= MoPqTWM2OD1{MD60JO69VQ>? MmHuNlU6QTl|NUK=
CLL PBMCs NWPHOZhzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHnPfVdFVVOR MYDJR|UxRTJwOTDuUS=> MWeyOVkyPzJ4Nx?=
U266 M2nFVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUG0NEDPxE1? MYq0PEBp MkD0O|kvPSViaX7obYJqfGmxbjDyZZRm MnTENlU{Ozl|M{K=
K562 NFK2T3RHfW6ldHnvckBCe3OjeR?= NWPvS3MyOSEQvF2= MVyzJIg> MUDJcohq[mm2aX;uJI9nKEGtdDDwbI9{eGixconsZZRqd25? M{L4dlI2ODF2N{e1
K562 NXfmN3E{TnWwY4Tpc44hSXO|YYm= MlWxNUDPxE1? MVmzJIg> NVLkXnlmUW6qaXLpeIlwdiCxZjDQO|BUPkticHjvd5Bpd3K7bHH0bY9v NHOyOIQzPTBzNEe3OS=>
K562 M2Doe2Z2dmO2aX;uJGF{e2G7 NUfuRYYyOSEQvF2= NXTKfFBXOyCq NHfMfIVKdmirYnn0bY9vKG:oIFfTT|MheGixc4Doc5J6dGG2aX;u MV6yOVAyPDd5NR?=
K562 M1uzNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWixJO69VQ>? NGHWVFg4OiCq M2n3emlvcGmkaYTpc44hd2ZicILvcIln\XKjdHnvci=> MlX4NlUxOTR5N{W=
Primary AML cell MWLGeY5kfGmxbjDBd5NigQ>? NUC5TWg{OSEQvF2= NWXRfZJ[OyCq MXXJcohq[mm2aX;uJI9nKEGtdDDwbI9{eGixconsZZRqd25? MXWyOVAyPDd5NR?=
Primary AML cell MUnGeY5kfGmxbjDBd5NigQ>? MlLaNUDPxE1? NV\T[FQzOyCq M3i3Z2lvcGmkaYTpc44hd2ZiUEewV|ZMKHCqb4PwbI9zgWyjdHnvci=> M4DlN|I2ODF2N{e1
Primary AML cell MXfGeY5kfGmxbjDBd5NigQ>? Mnv3NUDPxE1? M1rVPFMhcA>? M1\1[2lvcGmkaYTpc44hd2ZiR2PLN{BxcG:|cHjvdplt[XSrb36= MorBNlUxOTR5N{W=
Primary AML cell NGXkNWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mnr6NUDPxE1? MnPCN{Bp NHfheGtUfXCycnXzd4lwdiCxZjDyVm5CKHO7boTo[ZNqew>? M2TZXlI2ODF2N{e1
Microglia NUSxWYNITnWwY4Tpc44hSXO|YYm= Mn;0OUDPxE1? M{PUdFExKGh? MYPEUXNQ MXPE[YNz\WG|ZTDv[kBVVk[jIIPlZ5JmfGmxbjDmdo9uKEySUz3zeIlufWyjdHXkJEBxOTFyzsTEPVExSS:GOUGwRUBucWO{b3fsbYE> M1PrOFI1PjJ3Nki0
Primary CLL cell NF7kT5dHfW6ldHnvckBCe3OjeR?= NHnrWnIyKM7:TR?= MmTNNVUhdWmw Mmi5SG1UVw>? NXzBTpdCSmyxY3vzJGJEWi2rbnT1Z4VlKEyFUEGgd4VzcW6nLUWgZYN1cX[jdHnvci=> M1GxSlI1ODB7MkOz
JEKO-1 MnHNSpVv[3Srb36gRZN{[Xl? MnzsNUDPxE1? MoSzO|IhcA>? MknMTY5pcWKrdHnvckBw\iCDa4SgdIhwe3Cqb4L5cIF1cW:wIHnuJGloVS2|dHnteYxifGWmIFrFT28uOQ>? NVq5epRjOjN|NEG1OFE>
Granta-519 MlixSpVv[3Srb36gRZN{[Xl? NUi1cYVTOSEQvF2= M1PyRlIhcA>? MXPJcohq[mm2aX;uJI9nKEGtdDj0N|A5MSCyaH;zdIhwenmuYYTpc44> M3HlXVI{OzRzNUSx
Granta-519 NU\UTIM{TnWwY4Tpc44hSXO|YYm= MYWxJO69VQ>? MmHPNkBp Ml;2TY5pcWKrdHnvckBw\iCDa4Sod|Q4OylicHjvd5Bpd3K7bHH0bY9v M17EN|I{OzRzNUSx
JEKO-1 M1\kc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoLrNVAh|ryP NHPjU2M4OiCq MX\Jcohq[mm2aX;uJI9nKHC{b3zp[oVz[XSrb36gd4xq\2i2bIm= NV7VUY5EOjN|NEG1OFE>
JEKO-1 M4TtfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWm1JO69VQ>? MVS3NkBp MmXG[I9meyCwb4SgbY5lfWOnIHPlcIwh[3mlbHWgZZJz\XO2IH;yJIFxd3C2b4Ppdy=> M{TsdFI{Pjd4MkKw
MAVER-1 MonqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3nSPFUh|ryP Mni1O|IhcA>? NF\4Ulhld2W|IH7veEBqdmS3Y3WgZ4VtdCCleXPs[UBienKnc4Sgc5Ih[XCxcITvd4l{ MmLlNlM3PzZ{MkC=
MINO M4WzNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXj5RokyPSEQvF2= MmS0O|IhcA>? MojC[I9meyCwb4SgbY5lfWOnIHPlcIwh[3mlbHWgZZJz\XO2IH;yJIFxd3C2b4Ppdy=> MnLkNlM3PzZ{MkC=
SP53 NGSydXFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWfTWI1YOC5zIN88US=> MX23NkBp M3;obYRw\XNibn;0JIlv\HWlZTDj[YxtKGO7Y3zlJIFzemW|dDDvdkBieG:ydH;zbZM> MlzONlM3PzZ{MkC=
HH MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV;sWZo1OTBizszN NHPLNJc4OiCq MVHEUXNQ M1y5cGlv\HWldHnvckBw\iCjcH;weI9{cXNic3zp[4h1dHl? MljtNlI5ODF7NUm=
Myla NVqwOnZZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlHGNVAh|ryP MX[3NkBp M4DEOWROW09? M4fk[oRw\XNibn;0JIlv\HWlZTDhdI9xfG:|aYO= MlvINlI5ODF7NUm=
SR786 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYWxNEDPxE1? MXi3NkBp MVTEUXNQ NIf3Rmpld2W|IH7veEBqdmS3Y3WgZZBweHSxc3nz MVGyNlgxOTl3OR?=
HuT78 NYn4VpFDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXGxNEDPxE1? MnzNO|IhcA>? M1jFXmROW09? NVLvVJRo\G:nczDuc5QhcW6mdXPlJIFxd3C2b4Ppdy=> MYOyNlgxOTl3OR?=
MJ NX:ybGY4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1TzOlExKM7:TR?= MVu3NkBp M2rNT2ROW09? M1viWIRw\XNibn;0JIlv\HWlZTDhdI9xfG:|aYO= NF7RXJgzOjhyMUm1PS=>
DERL7 M4LKNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWjiVYdxOTBizszN NXizRZBFPzJiaB?= NHjoT4RFVVOR NIXFfWNld2W|IH7veEBqdmS3Y3WgZZBweHSxc3nz NWXvSW9uOjJ6MEG5OVk>
L1236 M2rLRWZ2dmO2aX;uJGF{e2G7 MlfmNVAh|ryP M1nFS|IhcA>? MYfJcohq[mm2aX;uJI9nKEGtdDDwbI9{eGixconsZZRqd25? MViyNlIyODh5Nx?=
L428 Mlf1SpVv[3Srb36gRZN{[Xl? M2fJdlExKM7:TR?= NES2dIszKGh? NWjPfW5JUW6qaXLpeIlwdiCxZjDBb5QheGixc4Doc5J6dGG2aX;u NXH3ZplYOjJ{MUC4O|c>
L591 MnrGSpVv[3Srb36gRZN{[Xl? MYGxNEDPxE1? NInoW4IzKGh? NX\BXnd7UW6qaXLpeIlwdiCxZjDBb5QheGixc4Doc5J6dGG2aX;u Ml3jNlIzOTB6N{e=
KMH-2 MVvGeY5kfGmxbjDBd5NigQ>? MVGxNEDPxE1? MVGyJIg> NIDB[2FKdmirYnn0bY9vKG:oIFHreEBxcG:|cHjvdplt[XSrb36= NWjGNlNCOjJ{MUC4O|c>
L1236 NFLiXmhHfW6ldHnvckBCe3OjeR?= MXS1JO69VQ>? NYG1[oNnOjRiaB?= MoPJRoxw[2u|IIPlZ5JmfGmxbjDv[kB1cGViQ1PMOS=> MVWyNlIyODh5Nx?=
L591 NHrjXpdHfW6ldHnvckBCe3OjeR?= MYm1JO69VQ>? NXzsU|FEOjRiaB?= NHPuPZNDdG:la4Ogd4VkemW2aX;uJI9nKHSqZTDDR2w2 M2G2WFIzOjFyOEe3
L1236 Mn:zRZBweHSxc3nzJGF{e2G7 NHjtPIo2KM7:TR?= NG\qSWszPCCq MWXJcoR2[3Srb36gc4Yh[XCxcITvd4l{ NUTSWIhROjJ{MUC4O|c>
L591 MlXhRZBweHSxc3nzJGF{e2G7 MkjHOUDPxE1? MWiyOEBp MXLJcoR2[3Srb36gc4Yh[XCxcITvd4l{ NE\rSZQzOjJzMEi3Oy=>
U-87MG NIqxNWFHfW6ldHnvckBCe3OjeR?= NGrk[GgyODBibl2= NX;XOXhHOjRiaB?= MVrEUXNQ MojPTY5pcWKrdHnvckBw\iBiY3XscEBucWe{YYTpc44> MojMNlIxPzl4MEm=
SW1783 NUTMSYJFTnWwY4Tpc44hSXO|YYm= NGHzTZkyODBibl2= Ml7UNlQhcA>? NHfhWW9FVVOR NHnkO2xKdmirYnn0bY9vKG:oIDDj[YxtKG2rZ4LheIlwdg>? Ml7MNlIxPzl4MEm=
U-87MG NF32dZJHfW6ldHnvckBCe3OjeR?= NWjWSoN5PSEQvF2= M4jscFI1KGh? NEDqUZBFVVOR NFe1b4RKdmirYnn0bY9vKG:oIFHreEBxcG:|cHjvdplt[XSrb36gd5Vje3SjboTpZYxtgQ>? MmXzNlIxPzl4MEm=
SW1783 NHLielBHfW6ldHnvckBCe3OjeR?= MoDVOUDPxE1? NYXjXWJPOjRiaB?= NWXtS5Y2TE2VTx?= MknZTY5pcWKrdHnvckBw\iCDa4SgdIhwe3Cqb4L5cIF1cW:wIIP1ZpN1[W62aXHscJk> NYryd3JXOjJyN{m2NFk>
U-373MG MV3GeY5kfGmxbjDBd5NigQ>? MXW1JO69VQ>? M2Oxd|I1KGh? NFqyRXhFVVOR MYLJcohq[mm2aX;uJI9nKEGtdDDwbI9{eGixconsZZRqd25ic4Xid5RidnSrYXzsfS=> NI\wSmozOjB5OU[wPS=>
SK-MG3 NWXNO|IxTnWwY4Tpc44hSXO|YYm= M2\PZlUh|ryP NVjHeZp3OjRiaB?= NWSyfHMzTE2VTx?= MlfiTY5pcWKrdHnvckBw\iCDa4SgdIhwe3Cqb4L5cIF1cW:wIIP1ZpN1[W62aXHscJk> M3rYelIzODd7NkC5
SU-DHL-5 MUHGeY5kfGmxbjDBd5NigQ>? M4TPOFEh|ryP MkG4NlQhcA>? M4jseGROW09? MU\JcoR2[3Srb36gc4Yh[XCxcITvd4l{ M4DTSVIxQTV7NkC2
WSU-NHL M4Ps[WZ2dmO2aX;uJGF{e2G7 NXfCWGwxOSEQvF2= M1fGOFI1KGh? NF7S[Y1FVVOR M3Gzcmlv\HWldHnvckBw\iCjcH;weI9{cXN? M1Pj[VIxQTV7NkC2
CCRF-SB MlfUSpVv[3Srb36gRZN{[Xl? MXyxJO69VQ>? NI\QRo4zPCCq MmnOSG1UVw>? NIHrb4ZKdmS3Y4Tpc44hd2ZiYYDvdJRwe2m| MVuyNFk2QTZyNh?=
INA-6 MWHGeY5kfGmxbjDBd5NigQ>? NHT5PZo2KM7:TR?= M4H6RVYhcA>? MoDHTY5pcWKrdHnvckBw\iCSSUPLM2FsfCCjbnSgSXJMKHCjdHj3ZZk> NGD4ToszODVyNUG1PC=>
LB M3XtXmZ2dmO2aX;uJGF{e2G7 NXXo[pkzPSEQvF2= NF:2NYM3KGh? MmC4TY5pcWKrdHnvckBw\iCSSUTLM2FsfCCjbnSgSXJMKHCjdHj3ZZk> NXTnV5RiOjB3MEWxOVg>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
PUMA / p53 ; 

PubMed: 28008149     


Parental and p53-KD HCT116 cells were treated with 10 μmol/L idelalisib for 24 hours. PUMA expression was analyzed by Western blotting.

Bim / Bcl-xl / Bid / Mcl-1; 

PubMed: 28008149     


HCT116 cells treated with 10 μmol/L idelalisib at indicated time point. The expression of indicated Bcl-2 family members was analyzed by Western blotting.

p-p65; 

PubMed: 28008149     


HCT116 cells were treated with 10 μmol/L idelalisib at indicated time point. p-p65 (S536) and p65 expression was analyzed by Western blotting.

p-AKT / AKT; 

PubMed: 28008149     


HCT116 cells were treated with 10 μmol/L idelalisib at indicated time point. Total AKT and p-AKT expression was analyzed Western blotting.

Cleaved caspase 3 / Cleaved caspase 9; 

PubMed: 28008149     


HepG2 cells were treated with 5μmol/L idelalisib at indicated time point. Cleaved-caspase 3 and 9 were analyzed by western blotting.

Mcl-1 / Bcl-2 / Bid / Bcl-xl / Noxa / Bak / Bax ; 

PubMed: 30224718     


HepG2 cells were treated with 5 μmol/L idelalisib at indicated time points. The expression of indicated Bcl-2 family members was analyzed by western blotting and normalized to β-actin. The data represent the mean ± SD of three independent experiments. **P < 0.01 (one-way ANOVA with Tukey’s post hoc test).

p-FoxO3a / FoxO3a; 

PubMed: 30224718     


HepG2 cells were treated with 5 μmol/L idelalisib for 24 h. Indicated protein expression was analyzed by western blotting and p-FoxO3a normalized to FoxO3a, p-AKT normalized to AKT. The data represent the mean ± SD of three independent experiments. **P < 0.01 (one-way ANOVA with Tukey’s post hoc test). 

Akt(T308) / PDK1(S241) / GSK-3β(S9); 

PubMed: 27342398     


JeKo-1, Mino, and Granta 519 cells or cells from four different MCL patients were serum-starved for 1h and then treated with DMSO, or with 0.5, 1, or 3μM for 1h; the cells were then co-cultured with IgM (10ng/μL) for 15min before harvesting. Cell extracts were prepared, and 30μg (cell lines) or 50μg (primary cells) protein was loaded for immunoblot analyses. The effects of idelalisib on Akt (Thr308) and total Akt, PDK1 (Ser241) and total PDK1, GS3K-3β (Ser9) and total GSK-3β protein expression levels were detected in (A) JeKo-1, Mino and Granta 519 cells.

28008149 30224718 27342398
Growth inhibition assay
Cell viability; 

PubMed: 28008149     


Indicated cell lines were treated with different concentrations of idelalisib for 72 hours. Cell proliferation was determined by MTS assay. Results were expressed as means ± SD of three independent experiments.

Cell viability; 

PubMed: 30224718     


The indicated cell lines were treated with increasing concentrations of idelalisib for 72 h. Cell viability was determined by MTS assay.

28008149 30224718

Protocol

Kinase Assay:[2]
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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]
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  • 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)
Water Insoluble
Ethanol '23 mg/mL
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
2% DMSO+20%PEG 300+ddH2O
For best results, use promptly after mixing.
5mg/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
Smiles CCC(NC1=C2N=C[NH]C2=NC=N1)C3=NC4=CC=CC(=C4C(=O)N3C5=CC=CC=C5)F

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03582098 Completed Drug: Idelalisib|Drug: Rituximab Chronic Lymphocytic Leukaemia Gilead Sciences September 12 2018 --
NCT03151057 Recruiting Drug: Idelalisib 100 MG|Drug: Placebo Oral Tablet 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 Recruiting Drug: Idelalisib Follicular Non-Hodgkin''s Lymphoma Refractory Gilead Sciences May 25 2018 --
NCT03310190 Recruiting -- Chronic Lymphocytic Leukemia AbbVie January 10 2018 --

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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

PI3K Signaling Pathway Map

PI3K Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID