CAL-101 (Idelalisib, GS-1101) 化学構造
分子量: 415.42

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製品説明

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製品の説明

生物活性

製品説明 CAL-101 (Idelalisib, GS-1101)は、2.5nMのIC50によるp110δの選択的なPI3KクラスI阻害剤です。
ターゲット p110δ
IC50 2.5 nM [1]
In vitro試験 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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
MEC1 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIS5fpdFVVOR MUPJR|UxRTJyLkSg{txO NFHKNo4zPTl7OUO1Ni=>
CLL PBMCs M{HM[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUjRc4ZOTE2VTx?= MmK4TWM2OD1{Lkmgcm0> NWToZ295OjV7MUeyOlc>
U266 NEP4eHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVTnW|VkPDBizszN MkjBOFghcA>? NW\DUJJTPzlwNTWgbY5pcWKrdHnvckBz[XSn MXGyOVM{QTN|Mh?=
K562 MlXsSpVv[3Srb36gRZN{[Xl? Mnn0NUDPxE1? MYezJIg> NFnR[5pKdmirYnn0bY9vKG:oIFHreEBxcG:|cHjvdplt[XSrb36= MYOyOVAyPDd5NR?=
K562 M1nSO2Z2dmO2aX;uJGF{e2G7 M2GxTlEh|ryP NVTqVIg3OyCq M4HsRWlvcGmkaYTpc44hd2ZiUEewV|ZMKHCqb4PwbI9zgWyjdHnvci=> MWKyOVAyPDd5NR?=
K562 MYDGeY5kfGmxbjDBd5NigQ>? MkDpNUDPxE1? NHfWPXU{KGh? MUjJcohq[mm2aX;uJI9nKEeVS{OgdIhwe3Cqb4L5cIF1cW:w NIjKbI4zPTBzNEe3OS=>
K562 NYjxNGdxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHL4[mwyKM7:TR?= M3jHSFczKGh? M4fMZmlvcGmkaYTpc44hd2ZicILvcIln\XKjdHnvci=> MnLiNlUxOTR5N{W=
Primary AML cell NH\EUmhHfW6ldHnvckBCe3OjeR?= M{XCflEh|ryP NXP3d4hFOyCq M1nCV2lvcGmkaYTpc44hd2ZiQXv0JJBpd3OyaH;yfYxifGmxbh?= MkXSNlUxOTR5N{W=
Primary AML cell NITWWW5HfW6ldHnvckBCe3OjeR?= NWO3doQ1OSEQvF2= MV:zJIg> M2PKdmlvcGmkaYTpc44hd2ZiUEewV|ZMKHCqb4PwbI9zgWyjdHnvci=> MmHqNlUxOTR5N{W=
Primary AML cell MnLxSpVv[3Srb36gRZN{[Xl? MVmxJO69VQ>? M3jGTFMhcA>? MYfJcohq[mm2aX;uJI9nKEeVS{OgdIhwe3Cqb4L5cIF1cW:w MlG3NlUxOTR5N{W=
Primary AML cell NH;6ToxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2KyTFEh|ryP NIGwNGs{KGh? NH;OVXZUfXCycnXzd4lwdiCxZjDyVm5CKHO7boTo[ZNqew>? MlPINlUxOTR5N{W=
Microglia Mme4SpVv[3Srb36gRZN{[Xl? MVK1JO69VQ>? MXGxNEBp NUfQT5ZWTE2VTx?= NHPad45F\WO{ZXHz[UBw\iCWTl\hJJNm[3KndHnvckBnem:vIFzQV{1{fGmvdXzheIVlKCCyMUGw{tRFQTFyQT;EPVExSSCvaXPyc4dtcWF? NUXLd4pIOjR4MkW2PFQ>
Primary CLL cell NHflV25HfW6ldHnvckBCe3OjeR?= MlXPNUDPxE1? NV\WRVVDOTVibXnu NVnTWHFMTE2VTx?= MV\CcI9kc3NiQlPSMYlv\HWlZXSgUGNROSC|ZYLpcoUuPSCjY4TpeoF1cW:w MkHnNlQxODl{M{O=
JEKO-1 M3G3UmZ2dmO2aX;uJGF{e2G7 NHPZdmcyKM7:TR?= M3\ze|czKGh? NXn6TlY5UW6qaXLpeIlwdiCxZjDBb5QheGixc4Doc5J6dGG2aX;uJIlvKEmpTT3zeIlufWyjdHXkJGpGU09vMR?= NFXrZlYzOzN2MUW0NS=>
Granta-519 NFroPZZHfW6ldHnvckBCe3OjeR?= M3vrTVEh|ryP M4iwbVIhcA>? NHPoXWlKdmirYnn0bY9vKG:oIFHreEh1OzB6KTDwbI9{eGixconsZZRqd25? M2nwc|I{OzRzNUSx
Granta-519 NV;VbZV1TnWwY4Tpc44hSXO|YYm= M4TxNVEh|ryP NXTielFpOiCq MkLaTY5pcWKrdHnvckBw\iCDa4Sod|Q4OylicHjvd5Bpd3K7bHH0bY9v NFX5PZgzOzN2MUW0NS=>
JEKO-1 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYHLdVdkOTBizszN NUDJWm83PzJiaB?= MYjJcohq[mm2aX;uJI9nKHC{b3zp[oVz[XSrb36gd4xq\2i2bIm= NED2XIszOzN2MUW0NS=>
JEKO-1 M16zeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX7zRpZRPSEQvF2= MX:3NkBp NF;PR5Rld2W|IH7veEBqdmS3Y3WgZ4VtdCCleXPs[UBienKnc4Sgc5Ih[XCxcITvd4l{ MkK5NlM3PzZ{MkC=
MAVER-1 NFfEPHVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3vxNlUh|ryP NIXVfVM4OiCq MUjkc4V{KG6xdDDpcoR2[2ViY3XscEBkgWOuZTDhdpJme3Rib4KgZZBweHSxc3nz MV6yN|Y4PjJ{MB?=
MINO NYK1dJRUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnzoOUDPxE1? M4jQbVczKGh? NI\XSYhld2W|IH7veEBqdmS3Y3WgZ4VtdCCleXPs[UBienKnc4Sgc5Ih[XCxcITvd4l{ NXjoWYRkOjN4N{[yNlA>
SP53 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnnzNE4yKM7:TR?= MU[3NkBp M2rDd4Rw\XNibn;0JIlv\HWlZTDj[YxtKGO7Y3zlJIFzemW|dDDvdkBieG:ydH;zbZM> M1frbFI{Pjd4MkKw
HH NEOyTYJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUCxNEDPxE1? NHXRWpM4OiCq MkPqSG1UVw>? MYHJcoR2[3Srb36gc4Yh[XCxcITvd4l{KHOuaXfoeIx6 Mn\KNlI5ODF7NUm=
Myla M4D0dmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4[1UFExKM7:TR?= NUPXN|U4PzJiaB?= MnnwSG1UVw>? NVL4WnN[\G:nczDuc5QhcW6mdXPlJIFxd3C2b4Ppdy=> M2\Q[lIzQDBzOUW5
SR786 M325b2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3;iSFExKM7:TR?= Mor2O|IhcA>? NGTzSXBFVVOR M3jXRYRw\XNibn;0JIlv\HWlZTDhdI9xfG:|aYO= NW\WblJiOjJ6MEG5OVk>
HuT78 M2Lkfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYLs[FVtOTBizszN NGXLbZo4OiCq MXTEUXNQ NHr0bnRld2W|IH7veEBqdmS3Y3WgZZBweHSxc3nz NXXtU5hbOjJ6MEG5OVk>
MJ NWPWVll7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml\iNVAh|ryP MnnEO|IhcA>? MVfEUXNQ MUfkc4V{KG6xdDDpcoR2[2ViYYDvdJRwe2m| MWOyNlgxOTl3OR?=
DERL7 NIrkR|JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWjHbplqOTBizszN NIXYOZY4OiCq M1njTmROW09? NVr6WYtn\G:nczDuc5QhcW6mdXPlJIFxd3C2b4Ppdy=> MlPvNlI5ODF7NUm=
L1236 MVLGeY5kfGmxbjDBd5NigQ>? NFHCdXAyOCEQvF2= MlfPNkBp MmrNTY5pcWKrdHnvckBw\iCDa4SgdIhwe3Cqb4L5cIF1cW:w MlLhNlIzOTB6N{e=
L428 NXXMfGhKTnWwY4Tpc44hSXO|YYm= NEiydVEyOCEQvF2= NFTCTGczKGh? MX;Jcohq[mm2aX;uJI9nKEGtdDDwbI9{eGixconsZZRqd25? NVPLcI5zOjJ{MUC4O|c>
L591 NGi4SWpHfW6ldHnvckBCe3OjeR?= NHzyXYgyOCEQvF2= NEjCRokzKGh? MULJcohq[mm2aX;uJI9nKEGtdDDwbI9{eGixconsZZRqd25? MUKyNlIyODh5Nx?=
KMH-2 MlLESpVv[3Srb36gRZN{[Xl? MWmxNEDPxE1? M4nj[|IhcA>? NYnId3F3UW6qaXLpeIlwdiCxZjDBb5QheGixc4Doc5J6dGG2aX;u NG\Tc20zOjJzMEi3Oy=>
L1236 NHvESllHfW6ldHnvckBCe3OjeR?= NHG5XVE2KM7:TR?= Ml7ENlQhcA>? Mm\XRoxw[2u|IIPlZ5JmfGmxbjDv[kB1cGViQ1PMOS=> NW\3PJF2OjJ{MUC4O|c>
L591 MWHGeY5kfGmxbjDBd5NigQ>? NV3zS2xLPSEQvF2= NFH0dmgzPCCq M1uy[GJtd2OtczDz[YNz\XSrb36gc4YhfGinIFPDUFU> MnLQNlIzOTB6N{e=
L1236 MVTBdI9xfG:|aYOgRZN{[Xl? MmjtOUDPxE1? NXjFXG05OjRiaB?= NETqcXNKdmS3Y4Tpc44hd2ZiYYDvdJRwe2m| NHvPbHIzOjJzMEi3Oy=>
L591 MYTBdI9xfG:|aYOgRZN{[Xl? M{jIclUh|ryP M1viNlI1KGh? M4nGT2lv\HWldHnvckBw\iCjcH;weI9{cXN? MmHGNlIzOTB6N{e=
U-87MG NX7ufYZiTnWwY4Tpc44hSXO|YYm= NYXYemlIOTByIH7N NGi4SJgzPCCq M4rLWGROW09? MU\Jcohq[mm2aX;uJI9nKCClZXzsJI1q\3KjdHnvci=> NIPEVWszOjB5OU[wPS=>
SW1783 NFTjNXhHfW6ldHnvckBCe3OjeR?= M{mze|ExOCCwTR?= NF7VWmYzPCCq NUmwboxYTE2VTx?= M2\5Z2lvcGmkaYTpc44hd2ZiIHPlcIwhdWmpcnH0bY9v NVjUfJhMOjJyN{m2NFk>
U-87MG NXzxbJhmTnWwY4Tpc44hSXO|YYm= MorXOUDPxE1? MY[yOEBp NF2yS2NFVVOR NEDZO|RKdmirYnn0bY9vKG:oIFHreEBxcG:|cHjvdplt[XSrb36gd5Vje3SjboTpZYxtgQ>? NGjOSW4zOjB5OU[wPS=>
SW1783 Mn;vSpVv[3Srb36gRZN{[Xl? M{LUWlUh|ryP NUTwcplWOjRiaB?= MYjEUXNQ MnO3TY5pcWKrdHnvckBw\iCDa4SgdIhwe3Cqb4L5cIF1cW:wIIP1ZpN1[W62aXHscJk> M{LUeVIzODd7NkC5
U-373MG MnLTSpVv[3Srb36gRZN{[Xl? MYW1JO69VQ>? NWqxS4pWOjRiaB?= Mmm5SG1UVw>? NVvqd2o2UW6qaXLpeIlwdiCxZjDBb5QheGixc4Doc5J6dGG2aX;uJJN2[nO2YX70bYFtdHl? MWGyNlA4QTZyOR?=
SK-MG3 MlvnSpVv[3Srb36gRZN{[Xl? MmLFOUDPxE1? MnvqNlQhcA>? MmC4SG1UVw>? M1;lNGlvcGmkaYTpc44hd2ZiQXv0JJBpd3OyaH;yfYxifGmxbjDzeYJ{fGGwdHnhcIx6 NG\rTZUzOjB5OU[wPS=>
SU-DHL-5 MVLGeY5kfGmxbjDBd5NigQ>? M3HlSlEh|ryP MXeyOEBp NFT0bnpFVVOR NVf6RWtsUW6mdXP0bY9vKG:oIHHwc5B1d3Orcx?= NYDJc41zOjB7NUm2NFY>
WSU-NHL NUXMZmpTTnWwY4Tpc44hSXO|YYm= MX:xJO69VQ>? M4n1PFI1KGh? M3X1R2ROW09? NXXFT25EUW6mdXP0bY9vKG:oIHHwc5B1d3Orcx?= MnvxNlA6PTl4ME[=
CCRF-SB NHe4WJZHfW6ldHnvckBCe3OjeR?= MYWxJO69VQ>? M2nsW|I1KGh? M1PNWWROW09? MYPJcoR2[3Srb36gc4Yh[XCxcITvd4l{ NF7ldIozODl3OU[wOi=>
INA-6 NEDrZoJHfW6ldHnvckBCe3OjeR?= NH;ubHo2KM7:TR?= MlLMOkBp MV3Jcohq[mm2aX;uJI9nKFCLM1uvRYt1KGGwZDDFVmsheGG2aIfhfS=> MmC1NlA2ODVzNUi=
LB NInZPGZHfW6ldHnvckBCe3OjeR?= MVK1JO69VQ>? NYq3bWRiPiCq NGDSc|RKdmirYnn0bY9vKG:oIGDJOGswSWu2IHHu[EBGWkticHH0bJdigQ>? NWXNRVg5OjB3MEWxOVg>

... Click to View More Cell Line Experimental Data

In vivo試験
臨床試験 Currently under Phase II clinical trial in patients with relapsed or refractory hodgkin lymphoma.
特集

プロトコル (参考用のみ)

キナーゼアッセイ: [2]

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.

細胞アッセイ: [2]

細胞株 CLL B cells or healthy volunteer T cells or NK cells
濃度 0.01-100 μM
反応時間 48 hours
実験の流れ 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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download CAL-101 (Idelalisib, GS-1101) SDF
分子量 415.42
化学式

C22H18FN7O

CAS No. 870281-82-6
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 83 mg/mL warming (199.79 mM)
エタノール 23 mg/mL (55.36 mM)
<1 mg/mL (<1 mM)
In vivo 30% PEG 400 (dissolve first)+0.5% Tween 80+5% Propylene glycol 30mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* 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.
化学名 (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one

カスタマーフィードバック (4)


Click to enlarge
Rating
Source , , J Immunol, 2014, 192(5): 2063-70 . CAL-101 (Idelalisib, GS-1101) purchased from Selleck
Method Invasion Assay
Cell Lines Fibroblast-like synoviocytes
Concentrations 5 µM
Incubation Time 24 h
Results FLS were pretreated with INK007 (PI3Kδ), CAL-101 (PI3Kδ), IPI-145 (PI3Kδ/γ), or GDC-0941 (panPI3K) and cultured in Matrigel invasion chambers for 16 h. The PI3Kδ inhibitors decreased invasion by 50–60% (p < 0.04) compared with vehicle-treated control. As 眏Ỵ眐㠞眎膉癠 皐﷘ř᐀ŔřĀ 㺣癞帉癞

Click to enlarge
Rating
Source Cell Death Differ, 2014, 21(10), 1535-45. CAL-101 (Idelalisib, GS-1101) purchased from Selleck
Method Western blot
Cell Lines 293T cells
Concentrations 10 uM
Incubation Time 4 h
Results It treated PC-3 cells with AKT kinase inhibitor (CAL-101) to promote Par-4 translocation to the nucleus. As shown in figure , CAL-101 treatment promoted Par-4 nuclear translocation and diminished the interaction between Par-4 and Fbxo45 in the cytoplasm.

Click to enlarge
Rating
Source Acta Pharmacol Sin, 2013, 34(9),1201-7. CAL-101 (Idelalisib, GS-1101) purchased from Selleck
Method Western blot
Cell Lines Rh30-Myr-p110s cells
Concentrations 0-6.6 uM
Incubation Time 1 h
Results CAL-101 significantly inhibited the phosphorylation of Akt in Rh30-Myr-p110α cells at the concentration of 2.2 umol/L, but was required to inhibit Akt phosphorylation to the same extent in Rh30-Myr-p110γ cells.

Click to enlarge
Rating
Source Dr. Zhang of Tianjin Medical University. CAL-101 (Idelalisib, GS-1101) purchased from Selleck
Method Western blot
Cell Lines A549 cells
Concentrations 0-1 μM
Incubation Time 3 h
Results Reduction of AKT phosphorylation in A549 cells treated with CAL-101 was observed.

文献中の引用 (25)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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