Art. -Nr.: HY-10423

OSI-027

(Synonyms: ASP7486)

12 Cited Publications

Kundenbewertung

Based on 12 publication(s) in Google Scholar

OSI-027 (ASP7486) is a potent, selective, orally active and ATP-competitive mTOR kinase activity inhibitor with an IC₅₀ of 4 nM. OSI-027 targets both mTORC1 and mTORC2 with IC₅₀s of 22 nM and 65 nM, respectively.

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Reinheit: 99.95%
CAS. Nr.: 936890-98-1
Formel: C₂₁H₂₂N₆O₃
Molecular Weight:406.44

Speicherung:

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

OSI-027 Chemical Structure

CAS. Nr.: 936890-98-1

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Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (12)
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Protokoll
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

IC₅₀ & Target^[1]

mTOR

4 nM (IC₅₀)

mTORC1

22 nM (IC₅₀)

mTORC2

65 nM (IC₅₀)

PI3K-γ

0.42 μM (IC₅₀)

PI3K-α

1.3 μM (IC₅₀)

DNA-PK

1 μM (IC₅₀)

Autophagy

Alle mTOR Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
CAKI-1	IC₅₀	1.9 μM Compound: OSI027	Cytotoxicity against human Caki1 cells after 72 hrs by MTT assay Cytotoxicity against human Caki1 cells after 72 hrs by MTT assay	[PMID: 24445311]
COLO 205	IC₅₀	5.8 μM Compound: OSI027	Cytotoxicity against human COLO205 cells after 72 hrs by MTT assay Cytotoxicity against human COLO205 cells after 72 hrs by MTT assay	[PMID: 24445311]
DU-145	IC₅₀	4.1 μM Compound: OSI027	Cytotoxicity against human DU145 cells after 72 hrs by MTT assay Cytotoxicity against human DU145 cells after 72 hrs by MTT assay	[PMID: 24445311]
HCT-116	IC₅₀	5.6 μM Compound: OSI027	Cytotoxicity against human HCT116 cells after 72 hrs by MTT assay Cytotoxicity against human HCT116 cells after 72 hrs by MTT assay	[PMID: 24445311]
HOP-62	IC₅₀	41 μM Compound: OSI027	Cytotoxicity against human HOP62 cells after 72 hrs by MTT assay Cytotoxicity against human HOP62 cells after 72 hrs by MTT assay	[PMID: 24445311]
HT-29	IC₅₀	55 μM Compound: OSI027	Cytotoxicity against human HT-29 cells after 72 hrs by MTT assay Cytotoxicity against human HT-29 cells after 72 hrs by MTT assay	[PMID: 24445311]
OVCAR-3	IC₅₀	8.1 μM Compound: OSI027	Cytotoxicity against human OVCAR3 cells after 72 hrs by MTT assay Cytotoxicity against human OVCAR3 cells after 72 hrs by MTT assay	[PMID: 24445311]
SK-HEP1	IC₅₀	3.2 μM Compound: OSI027	Cytotoxicity against human SKHEP1 cells after 72 hrs by MTT assay Cytotoxicity against human SKHEP1 cells after 72 hrs by MTT assay	[PMID: 24445311]
SQ20B	IC₅₀	1.3 μM Compound: OSI027	Cytotoxicity against human SQ20B cells after 72 hrs by MTT assay Cytotoxicity against human SQ20B cells after 72 hrs by MTT assay	[PMID: 24445311]

In Vitro

OSI-027 is an ATP-competitive inhibitor, which targets both mTORC1 and mTORC2 with IC₅₀s of 22 nM and 65 nM. OSI-027 also inhibits PI3K-α, PI3K-γ and DNA-PK with IC₅₀s of 1.3 μM, 0.42 μM and 1.0 μM. OSI-027 inhibits mTOR signaling of phospho-4E-BP1 with an IC₅₀ of 1 μM^[1].

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

In Vivo

Effects on GEO colorectal xenograft growth treated with Rapamycin or OSI-027 for 12 days are consistent with our in vitro experiments. Treatment with Rapamycin (20 mg/kg) inhibits phospho-S6 and phospho-4E-BP1, while Akt phosphorylation is increased by 29%. In contrast, OSI-027 (65 mg/kg) inhibits both mTORC1 and mTORC2 effectors. After 2 hours, decreased 4E-BP1, Akt, and S6 phosphorylation is observed and inhibition of S6 and Akt is sustained for 24 hours. The plasma drug concentration of OSI-027 inversely correlated with these effects on mTORC1 and mTORC2 signaling. The median plasma drug concentration with OSI-027 is 21.3 μM at 2 hours and 14.9 μM at 8 hours. The in vivo efficacy of OSI-027 plus Sunitinib is tested in H292 human lung and Ovcar-5 human ovarian xenograft tumors. H292 tumors, treated with OSI-027 (50 mg/kg) for 21 days have 61% median tumor growth inhibition for the duration of treatment (TGI). Sunitinib (40 mg/kg) for 21 days had 47% median TGI. Combining OSI-027 with Sunitinib, however, has a median TGI of 100% with 59% maximal tumor regression, a statistically significant improvement over either agent alone. Ovcar-5 xenograft tumors treated with OSI-027 or Sunitinib have a 55% and 68% median TGI, respectively. OSI-027 administered with Sunitinib has a significantly better median TGI of 100% with 38% maximal tumor regression^[1].
In the Rapamycin (RAPA) group, three rats exhibit symptoms typical of LTx-aGVHD and die 27 to 35 days after liver transplantation (LT); the remaining five rats do not develop LTx-aGVHD symptoms and survive for more than 100 days. In contrast, seven rats in the OSI-027 group survive for more than 100 days without symptoms of LTx-aGVHD, and only one rat exhibits LTx-aGVHD symptoms and dies on day 33 after LT^[3].

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

Clinical Trial

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

Chemical Information

CAS. Nr. 936890-98-1
Appearance Solid
Molecular Weight 406.44
Formel C₂₁H₂₂N₆O₃
Color Light yellow to yellow
SMILES

O=C([C@H]1CC[C@H](C2=NC(C(N3)=CC4=C3C(OC)=CC=C4)=C5C(N)=NC=NN52)CC1)O
Synonyms

ASP7486
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

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

Publications (12)

All WB

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Journal Impact Factor

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
EBioMedicine

PP2AC Level Determines Differential Programming of p38-TSC-mTOR Signaling and Therapeutic Response to p38-Targeted Therapy in Colorectal Cancer. [Abstract]

2015 Nov 19;2(12):1944-56. PMID: 26844273

OSI-027 purchased from MedChemExpress. Usage Cited in: EBioMedicine. 2015 Nov 19;2(12):1944-56. [Abstract]

SW620 xenograft tumors are treated with SB202190 and OSI027 individually or in combination. The effect on signaling by p38 (P-MK2 and P-Hsp27) and mTOR (P-S6K1 and P-AKT) is analyzed by immunoblot. SB202190 achieves on-target inhibition by diminishes phosphorylation of MK2 and Hsp27. OSI-027 blocks signaling by both mTORC1 and mTORC2 by decreases phosphorylation of S6K1 and AKT. When SB202190 and OSI-027 are used in combination, all three kinases, p38, mTORC1 and mTORC2 are potently inhibited.
Cell Syst

A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations. [Abstract]

2018 Apr 25;6(4):424-443.e7. PMID: 29655704
Int J Mol Sci

Rapid and Robust Multi-Phenotypic Assay System for ALS Using Human iPS Cells with Mutations in Causative Genes. [Abstract]

2023 Apr 10;24(8):6987. PMID: 37108151
Biol Direct

Integrative genomics unveils basement membrane-related diagnostic markers and therapeutic targets in esophageal squamous cell carcinoma. [Abstract]

2024 Sep 11;19(1):79. PMID: 39256753
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
Cancers (Basel)

Drug Repurposing Applications to Overcome Male Predominance via Targeting G2/M Checkpoint in Human Esophageal Squamous Cell Carcinoma. [Abstract]

2022 Nov 28;14(23):5854. PMID: 36497337
Int J Clin Oncol

The adenosine-A2a receptor regulates the radioresistance of gastric cancer via PI3K-AKT-mTOR pathway. [Abstract]

2022 May;27(5):911-920. PMID: 35122587
Mol Biol Cell

Adenosine interaction with adenosine receptor A2a promotes gastric cancer metastasis by enhancing PI3K-AKT-mTOR signaling. [Abstract]

2019 Sep 1;30(19):2527-2534. PMID: 31339445
Biochem Biophys Res Commun

Effects of rapamycin and OSI-027 on α-SMA in lung tissue of SD rat pups with hyperoxic lung injury. [Abstract]

2021 Jun 4:556:39-44. PMID: 33836346
Mol Cell Toxicol

2021 Apr 1.
Oncotarget

MHY1485 ameliorates UV-induced skin cell damages via activating mTOR-Nrf2 signaling. [Abstract]

2017 Feb 21;8(8):12775-12783. PMID: 28061443

OSI-027 purchased from MedChemExpress. Usage Cited in: Oncotarget. 2017 Feb 21;8(8):12775-12783. [Abstract]

OSI-027, AZD-8055 and AZD-2014 almost completely block MHY1485-induced mTOR activation (p-mTOR/S6K1/Akt Ser473) in skin keratinocytes.

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 100 mg/mL (246.04 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

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

2.4604 mL

12.3019 mL

24.6039 mL

5 mM

0.4921 mL

2.4604 mL

4.9208 mL

10 mM

0.2460 mL

1.2302 mL

2.4604 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.

Molaritätsrechner

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

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (6.15 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: 2.5 mg/mL (6.15 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Protokoll

Kinase Assay^[1]

Assays of a panel of 40 other recombinant kinases including both protein and lipid kinases are performed at 100 mM ATP concentration by SelectScreen profiling service. A broad panel of kinases is tested at a single concentration of OSI-027 or OXA-01 (3 μM) to evaluate percent inhibition of each kinase or mutant variant, using the Ambit KinomeScan platform^[1].

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

Cell Assay^[1]

To study the effect of drug treatment on cellular signaling, Ovcar-3 cells are plated in normal growth medium. After 24 hours, serum is removed and cells are serum-starved overnight. Rapamycin, OSI-027 and OXA-01 are solubilized in DMSO and added to cells at varying concentrations. After a two-hour incubation cells are growth factor stimulated with 10 ng/mL Insulin for 3 to 5 minutes, then rinsed with cold PBS and lysed^[1].

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

Animal Administration^[1]

Mice^[1]
For xenograft models, cells are harvested, implanted s.c. in the right flank of nu/nu CD-1 mice and tumor growth is analyzed. Mice bearing GEO xenografts are treated for 12 days with OSI-027 (65mg/kg) or vehicle and tumors collected at 2, 8, and 24 hours. Tumor growth inhibition and regression calculations are included.
Rats^[2]
Specific pathogen-free female Lewis rats, male BN rats, male Lew-Tg(CAG-EGFP)YsRrrc rats and male Lew-TgYsRrrc rats are used. Orthotopic LT is undertaken. No antibiotics were used. Freshly prepared splenocytes (4×10⁸, suspended in 500 μL PBS) of Lew-Tg YsRrrc rats are infused into each recipient via the dorsal penile vein immediately after LT (within 30 min). LTx-aGVHD model rats are divided into three experimental groups: RAPA (1 mg/kg), OSI-027 (1 mg/kg) or control (equal quantity of vehicle) groups; treatments are administered via the vena caudalis from day 7 to day 15.

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

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (285 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Falcon BL, et al. Reduced VEGF production, angiogenesis, and vascular regrowth contribute to the antitumor properties of dual mTORC1/mTORC2 inhibitors. Cancer Res. 2011 Mar 1;71(5):1573-83. [Content Brief]

[2]. Mateo J, et al. A first in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies. Br J Cancer. 2016;114(8):889-896. [Content Brief]

[3]. Zhang Y, et al. PP2AC Level Determines Differential Programming of p38-TSC-mTOR Signaling and Therapeutic Response to p38-Targeted Therapy in Colorectal Cancer. EBioMedicine. 2015 Nov 19;2(12):1944-56. [Content Brief]

[4]. Zhi X, et al. OSI-027 modulates acute graft-versus-host disease after liver transplantation in a rat model. Liver Transpl. 2017 Sep;23(9):1186-1198. [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
DMSO	1 mM	2.4604 mL	12.3019 mL	24.6039 mL	61.5097 mL
	5 mM	0.4921 mL	2.4604 mL	4.9208 mL	12.3019 mL
	10 mM	0.2460 mL	1.2302 mL	2.4604 mL	6.1510 mL
	15 mM	0.1640 mL	0.8201 mL	1.6403 mL	4.1006 mL
	20 mM	0.1230 mL	0.6151 mL	1.2302 mL	3.0755 mL
	25 mM	0.0984 mL	0.4921 mL	0.9842 mL	2.4604 mL
	30 mM	0.0820 mL	0.4101 mL	0.8201 mL	2.0503 mL
	40 mM	0.0615 mL	0.3075 mL	0.6151 mL	1.5377 mL
	50 mM	0.0492 mL	0.2460 mL	0.4921 mL	1.2302 mL
	60 mM	0.0410 mL	0.2050 mL	0.4101 mL	1.0252 mL
	80 mM	0.0308 mL	0.1538 mL	0.3075 mL	0.7689 mL
	100 mM	0.0246 mL	0.1230 mL	0.2460 mL	0.6151 mL

Keywords

OSI-027

12 Cited Publications

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OSI-027

Kinase Inhibitor Library

PI3K/Akt/mTOR Compound Library

Stem Cell Signaling Compound Library

Anti-Cancer Compound Library

Clinical Compound Library

Autophagy Compound Library

Anti-Aging Compound Library

Drug Repurposing Compound Library

Antioxidant Compound Library

Differentiation Inducing Compound Library

Reprogramming Compound Library

Oxygen Sensing Compound Library

Glycolysis Compound Library

Cytoskeleton Compound Library

Orally Active Compound Library

Glutamine Metabolism Compound Library

Anti-Breast Cancer Compound Library

Anti-Lung Cancer Compound Library

Anti-Pancreatic Cancer Compound Library

Anti-Blood Cancer Compound Library

Anti-Cancer Metabolism Compound Library

Anti-Obesity Compound Library

Angiogenesis-Related Compound Library

Lipid Metabolism Compound Library

Glucose Metabolism Compound Library

Anti-Liver Cancer Compound Library

Anti-Colorectal Cancer Compound Library

Anti-Prostate Cancer Compound Library

Anti-Pulmonary Fibrosis Compound Library

Cancer Stem Cells Compound Library

Pain-Related Compound Library

Mitochondrial Protection Compound Library

Highly Selective Inhibitors Library

Highly Selective Activators Library

Cell Death Library

Serine/Threonine Kinase Inhibitor Library

Anti-Hematopathy Compound Library

Anti-Ovarian Cancer Compound Library

Multi-Target Compound Library

Radioprotector Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Drug Repurposing Compound Library Plus

Clinical Compound Library Plus

Bioactive Compound Library

Anti-Gastric Cancer Compound Library

Anti-Fibrosis Compound Library

Anti-Brain Cancer Compound Library

High-Throughput Bioactive Compound Library

Posttranslational Modification Library

RNA Binding Bioactive Compound Library

Lactylation Compound Library

Publications Citing Use of MedChemExpress (MCE) OSI-027

Alle mTOR Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (12)

Lösungsmittel & Löslichkeit

Protokoll

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

OSI-027 Related Classifications

HY-10423 Related Classifications