Home PI3K/Akt/mTOR PI3K inhibitor - mTOR inhibitor - Autophagy activator - Apoptosis related activator Apitolisib (GDC-0980)

Apitolisib (GDC-0980)

Catalog No.S2696 Synonyms: RG7422, GNE 390

For research use only.

Apitolisib (GDC-0980, RG7422, GNE 390) is a potent, class I PI3K inhibitor for PI3Kα/β/δ/γ with IC50 of 5 nM/27 nM/7 nM/14 nM in cell-free assays, respectively. Also a mTOR inhibitor with Ki of 17 nM in a cell-free assay, and highly selective versus other PIKK family kinases. Apitolisib activates autophagy and apoptosis simultaneously in pancreatic cancer cells. Phase 2.

Apitolisib (GDC-0980) Chemical Structure

CAS No. 1032754-93-0

Selleck's Apitolisib (GDC-0980) has been cited by 28 publications

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Biological Activity

Description Apitolisib (GDC-0980, RG7422, GNE 390) is a potent, class I PI3K inhibitor for PI3Kα/β/δ/γ with IC50 of 5 nM/27 nM/7 nM/14 nM in cell-free assays, respectively. Also a mTOR inhibitor with Ki of 17 nM in a cell-free assay, and highly selective versus other PIKK family kinases. Apitolisib activates autophagy and apoptosis simultaneously in pancreatic cancer cells. Phase 2.
Features A potent, selective, and orally available inhibitor of PI3Kα, β, δ, γ and mTOR.
Targets
p110α [1]
(Cell-free assay)		 p110δ [1]
(Cell-free assay)		 p110γ [1]
(Cell-free assay)		 mTOR [1]
(Cell-free assay)		 p110β [1]
(Cell-free assay)
5 nM 7 nM 14 nM 17 nM(Ki app) 27 nM
In vitro

GDC-0980 shows the potent and selective inhibitory activities against class I PI3K and mTOR kinase versus a large panel of kinases with Ki of 17 nM for mTOR and IC50 of 5 nM, 27 nM, 7 nM, and 14 nM for PI3Kα, β, δ, and γ, respectively. [1] In vitro, GDC-0980 significantly inhibits cell proliferation in PC3 and MCF7 cells with IC50 of 307 nM and 255 nM, respectively. [1] A recent study shows that GDC-0980 reduces cancer cell viability by inhibiting cell-cycle procession and inducing apoptosis with most potency in prostate (IC50 < 200 nM 50%), <500 nM 100%), breast (IC50 <200 nM 37%, <500 nM 78%) and NSCLC lines (IC50 <200 nM 29%, <500 nM 88%) and less potency in pancreatic (IC50 <200 nM 13%, <500 nM 67%) and melanoma cell lines (IC50 <200 nM 0%, <500 nM 33%). [2]
Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
insect cells NFrQ[pdHfW6ldHnvckBie3OjeR?= MlXmN|AhdWmwcx?= M2fvPGlvcGmkaYTpc44hd2ZiaIXtZY4hemWlb33ibY5idnRibWTPVkBmgHC{ZYPz[YQhcW5iaX7z[YN1KGOnbHzzJIF{e2W|c3XkJIF{KHCqb4PwbI9zgWyjdHnvckBw\iC{ZXPvcYJqdmGwdDCoS2ZRMS12LVXCVFEhdWWjc4Xy[YQh[W[2ZYKgN|AhdWmwczDifUBndHWxcnXzZ4Vv[2VicH;sZZJqgmG2aX;uJIF{e2G7LDDLbV0xNjBzN988US=> M{TyTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOUixO|E1Lz5{MUm4NVcyPDxxYU6=
PC3 M3rERmZ2dmO2aX;uJIF{e2G7 M{n5OWlvcGmkaYTpc44hd2ZiUFnLN{Bo[W2vYT3t[YRq[XSnZDDBb5QheGixc4Doc5J6dGG2aX;uJIF1KFOnckS3N{BqdiCqdX3hckBRSzNiY3XscJMh[nliRVzJV2EtKEmFNUC9NE4xOzcQvF2= M3XVR|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOUixO|E1Lz5{MUm4NVcyPDxxYU6=
MCF7.1 M{TDe2FvfGmycn;sbYZmemG2aY\lJIF{e2G7 MWjBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE2FRkeuNUBk\WyuczDlfJBz\XO|aX7nJGhGWjJiZ3Xu[UBi\nSncjDveoVzdmmpaISgbY5kfWKjdHnvckBjgSCFZXzsWIl1\XJvR3zvJIx2dWmwZYPj[Y5k\SCjc4PhfUwhUUN3ME2wMlI2Pc7:TR?= Mmj0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7OEG3NVQoRjJzOUixO|E1RC:jPh?=
PC3 Mm\NRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? MULBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFCFMzDj[YxteyCjZoTldkBwfmW{bnnnbJQhcW6ldXLheIlwdiCkeTDD[YxtXGm2ZYKtS4xwKGy3bXnu[ZNk\W6lZTDhd5NigSxiSVO1NF0xNjNyN988US=> MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl6MUexOEc,OjF7OEG3NVQ9N2F-
PC3 NEjxdHFCdnSrdIXtc5Ih[XO|YYm= MXSxJI1oN2up NIq4[FEyPCCmYYnz NXHPVJl3SW62aYT1cY9zKGGldHn2bZR6KGGpYXnud5QhcHWvYX6gVGM{KGOnbHzzJJhmdm:pcnHmeIVlKGmwIHH0bJlucWNiboWvcpUhdW:3c3WgZZN{\XO|ZXSgZZMh\GWuYYmgbY4hfHWvb4Kg[5Jwf3SqIHH0JFEhdWdxa3esJJBwKHGmIH\vdkAyPCCmYYnz MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl6MUexOEc,OjF7OEG3NVQ9N2F-
MCF7-neo MmeyRY51cXS3bX;yJIF{e2G7 M{W4SVEhdWdxa3e= M1zjbFIzKGSjeYO= NHnQV3FCdnSrdIXtc5Ih[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNR2Y4NW6nbzDj[YxteyCneIDy[ZN{cW6pIFjFVlIh\2WwZTD4[Y5w\3KjZoTl[EBqdiCjdHj5cYlkKG63L371JI1wfXOnIHHzd4V{e2WmIHHzJIRmdGG7IHnuJJR2dW:{IHfyc5d1cCCjdDCxJI1oN2upLDDwc{By\CCob4KgNlIh\GG7cx?= MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl6MUexOEc,OjF7OEG3NVQ9N2F-
PC3 Ml;sRY51cXS3bX;yJIF{e2G7 MVrBcpRqfHWvb4KgZYN1cX[rdImgZYdicW6|dDDoeY1idiCSQ{OgZ4VtdHNieHXuc4dz[W[2ZXSgbY4h[XSqeX3pZ{BvfS:wdTDtc5V{\SCjc4Pld5Nm\CCjczD0eY1weiC{ZXfy[ZN{cW:wIHH0JI1igGmvdX2geI9t\XKjdHXkJIRwe2V? NWPSO5FbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5PFE4OTRpPkKxPVgyPzF2PD;hQi=>
MCF7-neo NHPseWRCdnSrdIXtc5Ih[XO|YYm= NV3YVWJmSW62aYT1cY9zKGGldHn2bZR6KGGpYXnud5QhcHWvYX6gUWNHPy2wZX:gZ4VtdHNiZYjwdoV{e2mwZzDISXIzKGenbnWgfIVvd2e{YX\0[YQhcW5iYYTofY1q[yCwdT;ueUBud3W|ZTDhd5Nme3OnZDDhd{B1fW2xcjDy[Ydz\XO|aX;uJIF1KG2jeHnteY0hfG:uZYLheIVlKGSxc3W= NFzGZXc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUm4NVcyPCd-MkG5PFE4OTR:L3G+
PC3 NWnLOlY3SW62aYT1cY9zKGG|c3H5 MnzJNVQh\GG7cx?= M1;1UWFvfGm2dX3vdkBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGDDN{Bk\WyuczD4[Y5w\3KjZoTl[EBqdiCjdHj5cYlkKG63L371JI1wfXOnIHHzd4V{e2WmIHHzJJR2dW:{IIP0ZZNqeyCjdDDtZZhqdXWvIITvcIVz[XSnZDDkc5NmKG2nYYP1doVlKG:wIHThfUAyPA>? MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl6MUexOEc,OjF7OEG3NVQ9N2F-
MCF7-neo NEfBcW9CdnSrdIXtc5Ih[XO|YYm= MVKyNkBl[Xm| NHHIbnlCdnSrdIXtc5Ih[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNR2Y4NW6nbzDj[YxteyCneIDy[ZN{cW6pIFjFVlIh\2WwZTD4[Y5w\3KjZoTl[EBqdiCjdHj5cYlkKG63L371JI1wfXOnIHHzd4V{e2WmIHHzJJR2dW:{IIP0ZZNqeyCjdDDtZZhqdXWvIITvcIVz[XSnZDDkc5NmKG2nYYP1doVlKG:wIHThfUAzOg>? MnHTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7OEG3NVQoRjJzOUixO|E1RC:jPh?=
PC3 MVzGeY5kfGmxbjDhd5NigQ>? NGXlZpAyOCCvZz;r[y=> MV:2JIhzew>? NYLwcVRmUW6qaXLpeIlwdiCxZjDtWG9TSzJiaX6gbJVu[W5iUFOzJINmdGy|IIjlco9oemGodHXkJI1wfXOnIHHzd4V{e2WmIHHzJJJm\HWldHnvckBw\iCyaH;zdIhwenmuYYTl[EBCc3RibHX2[Ywh[XRiMUCgcYcwc2duIIDvJIFnfGW{IE[gbJJ{ M{\QdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MUm5NFc3Lz5{M{G5PVA4PjxxYU6=
PC3 MorRSpVv[3Srb36gZZN{[Xl? MWCxNEBu\y:tZx?= NFLlepE3KGi{cx?= MXTJcohq[mm2aX;uJI9nKG2WT2LDNUBqdiCqdX3hckBRSzNiY3XscJMhgGWwb3fyZYZ1\WRibX;1d4Uh[XO|ZYPz[YQh[XNicnXkeYN1cW:wIH;mJJBpd3OyaH;yfYxifGWmIIC3NHM3UyCuZY\lcEBifCBzMDDt[{9s\yxicH:gZYZ1\XJiNjDodpM> M2n6OFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MUm5NFc3Lz5{M{G5PVA4PjxxYU6=
insect cells Ml23SpVv[3Srb36gZZN{[Xl? MYqzNEBucW6| M3XaSWlvcGmkaYTpc44hd2ZiaIXtZY4hemWlb33ibY5idnRibWTPVkApOTN4MDD0c{AzPTR7IILld4llfWW|KTDlfJBz\XO|ZXSgbY4hcW6|ZXP0JINmdGy|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiR1\QMYxi[mWuZXSgOE1GSlBzIIDoc5NxcG:{eXzheIlwdiCjdDDUbJIuOzdxNE[gdoV{cWS3ZYOgbY5kfWKjdHXkJIZweiB|MDDtbY5{KGK7IF\SSXQh[XO|YYmsJGtqRTBwMEG3{txO M{LvdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5MEm2NFQxLz5{N{C5OlA1ODxxYU6=
PC3 NWTXcWhtSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NGDRbXc{KGSjeYO= NFW1R4VCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGDDN{Bk\WyuczDh[pRmeiB|IHThfZMh[nliQ3XscHRqfHKnLVfsc{Bie3OjeTygSWM2OD1yLkOx{txO Ml\lQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjdyOU[wOFAoRjJ5MEm2NFQxRC:jPh?=
VERO-E6 NUL2d25mXG:6aXPpeJkh[XO|YYm= MnS1OFghcHK| MkfzWI95cWOrdImgR2M2OCCjZ3HpcpN1KF[HUl:tSVYh[2WubIOg[IV1\XKvaX7l[EBifCB2ODDoc5VzeyCkeTDobYdpKGOxboTlcpQhcW2jZ3nu[{Ape2GvZTDjc45lcXSrb37zJIF{KDKhTFXZJJdqfGixdYSg[Zhxd3O3cnWgeI8hOC5yMTDNU2khW0GUUzDDc3YuOiC4aYL1d{ktKEOFNUC9NE42|ryP MlHqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVkzOjB7ND:nQmNpTU2ETEyvZV4>
VERO-E6 NH3uUnhHfW6ldHnvckBie3OjeR?= NVm0[Ww4PDhiaILz NHuxbG9F\XSncn3pcoF1cW:wIH;mJGlEPTBidnHseYV{KG[xcjDpcohq[mm2aX;uJI9nKFODUmOtR49XNTJiaX7keYNm\CCleYTveI95cWOrdImgc4YhXkWUTz3FOkBk\WyuczDh[pRmeiB2ODDoc5VzeyBiZYjwc5N2emVidH:gNE4xOSCPT1mgV2FTWyCFb2[tNkB3cXK3czDifUBpcWeqIHPvcpRmdnRiaX3h[4lv\yxiSVO1NF0zNjNzzszN NH\4RZI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQTJ{MEm0M{c,S2iHTVLMQE9iRg>?
Click to View More Cell Line Experimental Data
Assay
Methods Test Index PMID
Growth inhibition assay Cell viability 25221930
Western blot p-AKT / AKT / p-S6RP / S6RP / p-4EBP / 4EBP / p-eNOS / eNOS 23814482
In vivo In both PC-3 and MCF-7 neo/HER2 xenograft models, GDC-0980 at a dose of 1 mg/kg, exhibits significant antitumor activity by causing tumor growth delay. Furthermore, GDC-0980 results in tumor stasis or regressions at the maximum tolerated dose of 7.5 mg/kg. [1] In mice, intravenous GDC-0980 administration at 1 mg/kg leads to low clearance (Clp: 9.2 mL/min/kg, Vss: 1.7 L/kg). While, oral administration at 5 mg/kg in 80% PEG400 and at 50 mg/kg as a crystalline suspension in 0.5% methylcellulose/0.2% Tween-80 also results in favorable pharmacokinetic parameters. [1]

Protocol (from reference)

Kinase Assay:[1]
  • Enzymatic activity:

    Enzymatic activity of the Class I PI3K isoforms is measured using a fluorescence polarization assay that monitors formation of the product 3,4,5-inositoltriphosphate molecule as it competes with fluorescently labeled PIP3 for binding to the GRP-1 pleckstrin homology domain protein. An increase in phosphatidyl inositide-3-phosphate product results in a decrease in fluorescence polarization signal as the labeled fluorophore is displaced from the GRP-1 protein binding site. Class I PI3K isoforms are expressed and purified as heterodimeric recombinant proteins. PI3K isoforms are assayed under initial rate conditions in the presence of 10 mM Tris (pH 7.5), 25 μM ATP, 9.75 μM PIP2, 5% glycerol, 4 mM MgCl2, 50 mM NaCl, 0.05% (v/v) Chaps, 1 mM dithiothreitol, 2% (v/v) DMSO at the following concentrations for each isoform: PI3Kα,β at 60 ng/mL; PI3Kγ at 8 ng/mL; PI3Kδ at 45 ng/mL. After assay for 30 minutes at 25°C, reactions are terminated with a final concentration of 9 mM EDTA, 4.5 nM TAMRA-PIP3, and 4.2 μg/mL GRP-1 detector protein before reading fluorescence polarization on an Envision plate reader. IC50s are calculated from the fit of the dose−response curves to a 4-parameter equation.Human recombinant mTOR(1360−2549) is expressed and purified from insect cells and assayed using a Lanthascreen fluorescence resonance energy transfer format in which phosphorylation of recombinant green fluorescent protein (GFP)-4-EBP1 is detected using a terbium-labeled antibody to phospho-threonine 37/46 of 4-EBP1. Reactions are initiated with ATP and conducted in the presence of 50 mM Hepes (pH 7.5), 0.25 nM mTOR, 400 nM GFP-4E-BP1, 8 μM ATP, 0.01% (v/v) Tween 20, 10 mM MnCl2, 1 mM EGTA, 1 mM dithiothreitol, and 1% (v/v) DMSO. Assays are conducted under initial rate conditions at room temperature for 30 minutes before terminating the reaction and detecting product in the presence of 2 nM Tb-anti-p4E-BP1 antibody and 10 mM EDTA. Dose−response curves are fit to an equation for competitive tight-binding inhibition and apparent Ki' s are calculated using the determined Km for ATP of 6.1 μM.
Cell Research:[1]
  • Cell lines: PC3 and MCF7.1
  • Concentrations: 0 to 10 μM
  • Incubation Time: 72 hours or 96 hours
  • Method: Antiproliferative cellular assays are conducted using PC3 and MCF7.1 human tumor cell lines. MCF7.1 is an in vivo selected line and originally derived from the parental human MCF7 breast cancer cell line. Cell lines are cultured in RPMI supplemented with 10% fetal bovine serum, 100 units/mL penicillin, and 100 μg/mL streptomycin, 10 mM HEPES, and 2 mM glutamine at 3°C under 5% CO2. MCF7.1 cells or PC3 cells are seeded in 384-well plates in media at 1000 cells/well or 3000 cells/well, respectively, and incubated overnight prior to the addition of GDC-0980 to a final DMSO concentration of 0.5% v/v. MCF7.1 cells and PC3 cells are incubated for 3 days and 4 days, respectively, prior to the addition of CellTiter-Glo reagen and reading of luminescence using an Analyst plate reader. For antiproliferative assays, a cytostatic agent such as aphidicolin and a cytotoxic agent such as staurosporine are included as controls. Dose−response curves are fit to a 4-parameter equation and relative IC50s are calculated using Assay Explorer software.
Animal Research:[1]
  • Animal Models: PC3 and MCF7.1 cells are injected s.c. into the right hind flank of athymic nu/nu (nude) mice.
  • Dosages: ≤7.5 mg/kg
  • Administration: Administered via p.o.

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
0.5% methylcellulose+0.2% Tween 80
For best results, use promptly after mixing.

 30 mg/mL

Chemical Information

Molecular Weight 498.6
Formula

C23H30N8O3S
CAS No. 1032754-93-0
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=C(SC2=C1N=C(N=C2N3CCOCC3)C4=CN=C(N=C4)N)CN5CCN(CC5)C(=O)C(C)O

In vivo Formulation Calculator (Clear solution)

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%DMSO %

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
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Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT01487239 Completed Drug: [14C]-GDC-0980 Healthy Volunteer Genentech Inc. December 2011 Phase 1
NCT01455493 Completed Drug: GDC-0980 Endometrial Carcinoma Genentech Inc. December 2011 Phase 2
NCT01442090 Completed Drug: Everolimus|Drug: GDC-0980 Renal Cell Carcinoma Genentech Inc. October 2011 Phase 2
NCT01254526 Completed Drug: GDC-0980|Drug: bevacizumab|Drug: paclitaxel Breast Cancer Genentech Inc. December 2010 Phase 1
NCT00854126 Completed Drug: GDC-0980 Non-Hodgkin''s Lymphoma Solid Cancers Genentech Inc. May 2009 Phase 1
NCT00854152 Completed Drug: GDC-0980 Non-Hodgkin''s Lymphoma Solid Cancers Genentech Inc. March 2009 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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