製品番号: HY-10681

Gedatolisib

(別名: PKI-587; PF-05212384)

6 Cited Publications

カスタマーレビュー

Based on 6 publication(s) in Google Scholar

Gedatolisib (PKI-587) is a highly potent dual inhibitor of PI3Kα, PI3Kγ, and mTOR with IC₅₀s of 0.4 nM, 5.4 nM and 1.6 nM, respectively. Gedatolisib is equally effective in both complexes of mTOR, mTORC1 and mTORC2.

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純度: 99.89%
CAS 番号: 1197160-78-3
分子式: C₃₂H₄₁N₉O₄
分子量:615.73

保管条件:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

Gedatolisib 構造式

CAS 番号: 1197160-78-3

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数量

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生物活性
- 製品説明
- IC₅₀ & Target
- Cellular Effect
- 体外実験
- 体内実験
- 臨床実験
化学情報
Publications (6)
溶剤 & 溶解度
- 体外
純度とドキュメンテーション
参考文献
Help & FAQs
関連分類
Bioz

生物活性

製品説明

Gedatolisib (PKI-587) is a highly potent dual inhibitor of PI3Kα, PI3Kγ, and mTOR with IC₅₀s of 0.4 nM, 5.4 nM and 1.6 nM, respectively^[1]. Gedatolisib is equally effective in both complexes of mTOR, mTORC1 and mTORC2^[2].

IC₅₀ & Target^[1]^[3]

PI3Kα

0.4 nM (IC₅₀)

PI3Kα-H1047R

0.6 nM (IC₅₀)

PI3Kα-E545K

0.6 nM (IC₅₀)

PI3Kγ

5.4 nM (IC₅₀)

PI3Kβ

6 nM (IC₅₀)

PI3Kδ

6 nM (IC₅₀)

mTOR

1.6 nM (IC₅₀)

mTORC1

mTORC2

PI3K アイソフォーム固有の製品をすべて表示 :

mTOR アイソフォーム固有の製品をすべて表示 :

Cellular Effect

Cell Line	Type	Value	Description	References
A-431	IC₅₀	0.06 μM Compound: 6aa	Antiproliferative activity against human A431 cells harboring wild type EGFR mutant assessed as reduction in cell viability incubated for 72 hrs by celltiter-glo assay Antiproliferative activity against human A431 cells harboring wild type EGFR mutant assessed as reduction in cell viability incubated for 72 hrs by celltiter-glo assay	[PMID: 34971874]
BaF3	IC₅₀	0.1 μM Compound: 6aa	Antiproliferative activity against mouse BaF3 cells harboring EGFR L858R/T790M/C797S mutant assessed as reduction in cell viability incubated for 72 hrs by celltiter-glo assay Antiproliferative activity against mouse BaF3 cells harboring EGFR L858R/T790M/C797S mutant assessed as reduction in cell viability incubated for 72 hrs by celltiter-glo assay	[PMID: 34971874]
CNE-2	IC₅₀	0.2 μM Compound: 6aa	Antiproliferative activity against human CNE-2 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Antiproliferative activity against human CNE-2 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 34971874]
CNE-2	IC₅₀	2.97 μM Compound: PT-1	Antiproliferative activity against human CNE-2 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK-8 assay Antiproliferative activity against human CNE-2 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK-8 assay	[PMID: 38661655]
HCT-116	IC₅₀	0.51 μM Compound: 6aa	Antiproliferative activity against human HCT-116 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Antiproliferative activity against human HCT-116 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 34971874]
HCT-116	IC₅₀	0.98 μM Compound: PT-1	Antiproliferative activity against human HCT-116 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK-8 assay Antiproliferative activity against human HCT-116 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK-8 assay	[PMID: 38661655]
HeLa	IC₅₀	1.07 μM Compound: PT-1	Antiproliferative activity against human HeLa cells assessed as inhibition of cell growth incubated for 48 hrs by CCK-8 assay Antiproliferative activity against human HeLa cells assessed as inhibition of cell growth incubated for 48 hrs by CCK-8 assay	[PMID: 38661655]
HeLa	IC₅₀	5.51 μM Compound: 6aa	Antiproliferative activity against human HeLa cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Antiproliferative activity against human HeLa cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 34971874]
HepG2	IC₅₀	14.76 μM Compound: 6aa	Antiproliferative activity against human HepG2 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Antiproliferative activity against human HepG2 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 34971874]
HepG2	IC₅₀	3.6 μM Compound: PT-1	Antiproliferative activity against human HepG2 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK-8 assay Antiproliferative activity against human HepG2 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK-8 assay	[PMID: 38661655]
L02	IC₅₀	27.33 μM Compound: 6aa	Antiproliferative activity against human L02 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Antiproliferative activity against human L02 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 34971874]
L02	IC₅₀	4.38 μM Compound: PT-1	Antiproliferative activity against human L02 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK-8 assay Antiproliferative activity against human L02 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK-8 assay	[PMID: 38661655]
MCF7	IC₅₀	0.37 μM Compound: 6aa	Antiproliferative activity against human MCF7 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Antiproliferative activity against human MCF7 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 34971874]
MCF7	IC₅₀	1.49 μM Compound: PT-1	Antiproliferative activity against human MCF7 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK-8 assay Antiproliferative activity against human MCF7 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK-8 assay	[PMID: 38661655]
MDA-MB-231	IC₅₀	1.08 μM Compound: 6aa	Antiproliferative activity against human MDA-MB-231 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Antiproliferative activity against human MDA-MB-231 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 34971874]
MDA-MB-231	IC₅₀	2.47 μM Compound: PT-1	Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK-8 assay Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK-8 assay	[PMID: 38661655]
MDA-MB-361	IC₅₀	<10 nM Compound: 26, PKI-587	Inhibition of Akt S473 phosphorylation in human MDA-MB-361 cells by Western blotting Inhibition of Akt S473 phosphorylation in human MDA-MB-361 cells by Western blotting	[PMID: 20166697]
MDA-MB-361	IC₅₀	3 nM Compound: 1, PKI-587	Growth inhibition of human MDA-MB-361 cells after 72 hrs Growth inhibition of human MDA-MB-361 cells after 72 hrs	[PMID: 21763134]
MDA-MB-361	IC₅₀	4 nM Compound: 26, PKI-587	Cytotoxicity against human MDA-MB-361 cells Cytotoxicity against human MDA-MB-361 cells	[PMID: 20166697]
MDA-MB-361	IC₅₀	8 nM Compound: 26, PKI-587	Inhibition of Akt T308 phosphorylation in human MDA-MB-361 cells by Western blotting Inhibition of Akt T308 phosphorylation in human MDA-MB-361 cells by Western blotting	[PMID: 20166697]
NCI-H1975	IC₅₀	0.115 μM Compound: 6aa	Antiproliferative activity against human NCI-H1975 cells harboring EGFR L858R/T790M double mutant assessed as reduction in cell viability incubated for 72 hrs by celltiter-glo assay Antiproliferative activity against human NCI-H1975 cells harboring EGFR L858R/T790M double mutant assessed as reduction in cell viability incubated for 72 hrs by celltiter-glo assay	[PMID: 34971874]
PC-3	IC₅₀	11 nM Compound: 1, PKI-587	Growth inhibition of human PC3 cells after 72 hrs Growth inhibition of human PC3 cells after 72 hrs	[PMID: 21763134]
Sf9	IC₅₀	0.4 nM Compound: 1, PKI-587	Inhibition of human PI3Kalpha expressed in SF9 insect cells after 2 hrs by fluorescence polarization assay Inhibition of human PI3Kalpha expressed in SF9 insect cells after 2 hrs by fluorescence polarization assay	[PMID: 21763134]
Sf9	IC₅₀	11 nM Compound: 1, PKI-587	Inhibition of human PI3Kgamma expressed in SF9 insect cells after 2 hrs by fluorescence polarization assay Inhibition of human PI3Kgamma expressed in SF9 insect cells after 2 hrs by fluorescence polarization assay	[PMID: 21763134]

体外実験

Gedatolisib (PKI-587) shows good potency in cell growth inhibition assays using MDA-361 and PC3-MM2 cell lines with IC₅₀s of 4.0 and 13.1 nM, respectively^[1].
Gedatolisib shows potent suppression of phosphorylation of PI3K/mTOR signaling pathway proteins in MDA-361 tumor cells. Gedatolisib (0.03-3 μM; 4 hours) prevents the phosphorylation of Akt at Thr 308 and induces cleaved PARP at 30 nM^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis^[1]

Cell Line:

MDA-361 tumor cells
Concentration:

0.03, 0.1, 0.3, 1, and 3 μM
Incubation Time:

4 hours
Result:

Prevented the phosphorylation of Akt (pAkt) at threonine 308 (T308; IC₅₀=8 nM).

体内実験

Gedatolisib (PKI-587; administered i.v. at 20 mg/kg on days 1, 5, 9) exhibits potent antitumor efficacy against MDA-361 tumors in mice^[1].
Gedatolisib exhibits terminal elimination half-life (T_1/2 14.4 h) due to high plasma clearance (7 mL/min/kg) combined with large volumes of distribution (7.2 L/kg respectively) following i.v. administration (25 mg/kg) female nude mice^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Female nude mice bearing MDA-361 xenograft model^[1].
Dosage:

20 mg/kg
Administration:

Administered i.v. at 20 mg/kg on an intermittent regimen (days 1, 5, 9).
Result:

Caused regression of large staged (~900 mm³) tumors.
The minimum efficacious dose (MED) was determined to be 3 mg/kg against MDA-361 tumors and maximum tolerated single dose (MTD) was determined to be 30 mg/kg.

臨床実験

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

化学情報

CAS 番号 1197160-78-3
性状 Solid
分子量 615.73
分子式 C₃₂H₄₁N₉O₄
Color White to off-white
SMILES

CN(C1CCN(C(C2=CC=C(NC(NC3=CC=C(C4=NC(N5CCOCC5)=NC(N6CCOCC6)=N4)C=C3)=O)C=C2)=O)CC1)C
別名

PKI-587; PF-05212384
輸送条件

Room temperature in continental US; may vary elsewhere.

保管条件

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Publications (6)

All Cell Proliferation/Viability AssayIn Vivo Efficacy Study

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Journal Impact Factor

Nat Commun

Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine therapy-resistant breast cancer. [Abstract]

2021 Aug 25;12(1):5112. PMID: 34433817

Gedatolisib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2021 Aug 25;12(1):5112. [Abstract]

The efficacy of Fulvestrant (Fulv, 100 nM), CDK4/6 inhibitor (CDK4/6i) Palbociclib (Palbociclib isothiocyanate; 200 nM) and the dual PI3K/mTOR inhibitor (PI3K/mTORi) Gedatolisib (10 nM) as single agents or in double and triple combination, was assessed in M-S and MPF-R cells by crystal violet growth assay performed over 6 days.

Gedatolisib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2021 Aug 25;12(1):5112. [Abstract]

The efficacy of Fulvestrant (Fulv, 100 nM), CDK4/6 inhibitor (CDK4/6i) Palbociclib (Palbociclib isothiocyanate; 200 nM) and the dual PI3K/mTOR inhibitor (PI3K/mTORi) Gedatolisib (10 nM) as single agents or in double and triple combination, was assessed in T-S and TPF-R cells by crystal violet growth assay performed over 6 days.
Sci Transl Med

Dual PI3K/mTOR inhibition is required to combat resistance to CDK4/6 inhibitor and endocrine therapy in PIK3CA-mutant breast cancer. [Abstract]

2025 Dec 17;17(829):eadp5088. PMID: 41406241

Gedatolisib purchased from MedChemExpress. Usage Cited in: Sci Transl Med. 2025 Dec 17;17(829):eadp5088. [Abstract]

Combined Palbociclib- and Fulvestrant-resistant cells, M-S and T-S, and the corresponding resistant cells, MPF-R and TPF-R, were treated with different inhibitors of the PI3K/AKT/mTOR pathway including Alpelisib (HY-15244; Alp; 1 μM in M-S/MPF-R and 250 to 500 nM in T-S/TPF-R), Capivasertib (Cap; 250 to 500 nM in M-S/MPF-R and 100 nM in T-S/TPF-R), Sapanisertib (Sap; 10 nM in M-S/MPF-R and 5 nM in T-S/TPF-R), and Gedatolisib (HY-10681; Ged; 10 nM) in combination with Palbociclib (HY-50767; Palbo; 200 nM) and Fulvestrant (HY-13636; Fulv; 100 nM) (n = 3 independent biological replicates per group, performed in duplicates).

Gedatolisib purchased from MedChemExpress. Usage Cited in: Sci Transl Med. 2025 Dec 17;17(829):eadp5088. [Abstract]

Combined Palbociclib- and Fulvestrant-resistant cells (wild type ER+ breast cancer cells), ZPF-R, and the corresponding sensitive cells, Z-S, were treated with different inhibitors of PI3K/AKT/mTOR including Alpelisib (HY-15244; 6 μM), Capivasertib (50 nM), Sapanisertib (5 nM), and Gedatolisib (HY-10681; 5 nM) in combination with Palbociclib (HY-50767; 150 nM) and Fulvestrant (HY-13636; 100 nM) (n = 3 independent biological replicates per group, performed in duplicates).

Gedatolisib purchased from MedChemExpress. Usage Cited in: Sci Transl Med. 2025 Dec 17;17(829):eadp5088. [Abstract]

Triple combination with Gedatolisib (HY-10681), Palbociclib (HY-50767), and Fulvestrant (HY-13636) effectively inhibits growth of PIK3CA-mutant ER+ tumor xenografts resistant to combined palbociclib and fulvestrant. MPF-R cells (1 × 106) resistant to combined palbociclib and fulvestrant were injected into the mammary fat pads of NOG CIEA mice, and tumors were allowed to establish for 2 weeks to a size of ≈30 mm3. Mice were then treated with the combination of Fulvestrant (100 mg/kg, sc weekly), Palbociclib (25 mg/kg, oral gavage daily), and Capivasertib (100 mg/kg, oral gavage daily; n = 6) or Alpelisib (HY-15244; 25 mg/kg, oral gavage daily; n = 5). Tumor size was measured weekly. Average tumor growth curves measured weekly and Tumor volumes measured after excision.

Gedatolisib purchased from MedChemExpress. Usage Cited in: Sci Transl Med. 2025 Dec 17;17(829):eadp5088. [Abstract]

Gedatolisib efficiently reduced the viability of ER+ PIK3CA- or AKT1-mutant breast cancer PDOs resistant to Abemaciclib. Dose-effect curves of CDK4/6i Abemaciclib, dual PI3K/mTORi Gedatolisib (HY-10681), PI3Ki Alpelisib (HY-15244), and dual mTORC1/2i Sapanisertib at day 7 of treatment in three breast cancer PDOs, PDO-P40, PDO-P46, and PDO-P48 (n = 3 biological replicates per group), developed from ER+ breast tumors and selected because of their differing IC50 toward Abemaciclib.

Gedatolisib purchased from MedChemExpress. Usage Cited in: Sci Transl Med. 2025 Dec 17;17(829):eadp5088. [Abstract]

Effect of 1 μM Abemaciclib, Gedatolisib (HY-10681), Alpelisib (HY-15244), or Sapanisertib on viability of PDO-P40, PDO-P46, or PDO-P48 during 7 days of treatment. Data are presented as means ± SEM. Significant differences are calculated by one-way ANOVA test (*P < 0.05, **P < 0.01, and ***P < 0.001).
Sci Transl Med

PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]

2018 Jul 18;10(450):eaaq1093. PMID: 30021885
Molecules

In Vitro and in Vivo Activity of mTOR Kinase and PI3K Inhibitors Against Leishmania donovani and Trypanosoma brucei. [Abstract]

2020 Apr 23;25(8):1980. PMID: 32340370
Am J Transl Res

PKI-587 enhances chemosensitivity of oxaliplatin in hepatocellular carcinoma through suppressing DNA damage repair pathway (NHEJ and HR) and PI3K/AKT/mTOR pathway. [Abstract]

2019 Aug 15;11(8):5134-5149. PMID: 31497229
bioRxiv

CDK4/6 inhibition sensitizes breast cancer to NK cell therapy by inducing immune-interactive surface proteins. [Abstract]

2026 Apr 22:2026.04.19.719504. PMID: 42079201

溶剤 & 溶解度

体外:

H₂O : 20 mg/mL (32.48 mM; adjust pH to 2 with 1 M HCL)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.6241 mL

8.1204 mL

16.2409 mL

5 mM

0.3248 mL

1.6241 mL

3.2482 mL

10 mM

0.1624 mL

0.8120 mL

1.6241 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

モル濃度計算機

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

濃度濃度

体積体積

分子量分子量

希釈計算機

濃度 _(開始) × 体積 _(開始) = 濃度 _(終了) × 体積 _(終了)

濃度 _(開始) 濃度 _(開始)

体積 _(開始) 体積 _(開始)

濃度 _(終了) 濃度 _(終了)

体積 _(終了) 体積 _(終了)

純度とドキュメンテーション

バッチを選択:

純度: 99.98%

Assay: 99.98%

ee.: 99.98%

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COA (2659 KB)
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HNMR (2659 KB)
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参考文献

[1]. Venkatesan AM, et al. Bis(morpholino-1,3,5-triazine) derivatives: potent adenosine 5'-triphosphate competitive phosphatidylinositol-3-kinase/mammalian target of rapamycin inhibitors: discovery of compound 26 (PKI-587), a highly efficacious dual inhibitor. J Med Chem. 2010, 53(6), 2636-2645. [Content Brief]

[2]. Freitag H, et al. Inhibition of mTOR's Catalytic Site by PKI-587 Is a Promising Therapeutic Option for Gastroenteropancreatic Neuroendocrine Tumor Disease. Neuroendocrinology. 2017;105(1):90-104. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
H₂O	1 mM	1.6241 mL	8.1204 mL	16.2409 mL	40.6022 mL
	5 mM	0.3248 mL	1.6241 mL	3.2482 mL	8.1204 mL
	10 mM	0.1624 mL	0.8120 mL	1.6241 mL	4.0602 mL
	15 mM	0.1083 mL	0.5414 mL	1.0827 mL	2.7068 mL
	20 mM	0.0812 mL	0.4060 mL	0.8120 mL	2.0301 mL
	25 mM	0.0650 mL	0.3248 mL	0.6496 mL	1.6241 mL
	30 mM	0.0541 mL	0.2707 mL	0.5414 mL	1.3534 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Keywords

Gedatolisib

6 Cited Publications

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Gedatolisib

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MedChemExpress（MCE）の使用を引用している文献 Gedatolisib

PI3K アイソフォーム固有の製品をすべて表示

mTOR アイソフォーム固有の製品をすべて表示

生物活性

化学情報

Publications (6)

溶剤 & 溶解度

純度とドキュメンテーション

参考文献

Help & FAQs

Complete Stock Solution Preparation Table

Gedatolisib 関連分類

HY-10681 関連分類