Referencia número: HY-15466

Izorlisib

(Synonyms: CH5132799)

3 Cited Publications

Revisión del cliente

Based on 3 publication(s) in Google Scholar

Izorlisib (CH5132799) is a selective class I PI3K inhibitor. Izorlisib inhibits class I PI3Ks, particularly PI3Kα, with an IC₅₀ of 14 nM.

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Pureza: 99.01%
No. CAS: 1007207-67-1
Fòrmula: C₁₅H₁₉N₇O₃S
Peso molecular:377.42

Almacenamiento:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

Izorlisib Chemical Structure

No. CAS: 1007207-67-1

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Fluorescent Dye

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

Actividad biológica
- Descripciòn
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Ensayo clínico
Chemical Information
Publications (3)
Solvente y solubilidad
- In Vitro
- In Vivo
Protocolo
Pureza y Documentación
Referencias
Help & FAQs
Classifications
Bioz

Actividad biológica

Descripciòn

Izorlisib (CH5132799) is a selective class I PI3K inhibitor. Izorlisib inhibits class I PI3Ks, particularly PI3Kα, with an IC₅₀ of 14 nM.

IC₅₀ & Target^[1]

PI3Kα

14 nM (IC₅₀)

PI3Kα-H1047R

5.6 nM (IC₅₀)

PI3Kα-E545K

6.7 nM (IC₅₀)

PI3Kα-E542K

6.7 nM (IC₅₀)

PI3Kγ

36 nM (IC₅₀)

PI3Kβ

120 nM (IC₅₀)

PI3Kδ

500 nM (IC₅₀)

PI3KC2β

5.3 μM (IC₅₀)

mTOR

1.6 μM (IC₅₀)

Ver todos los productos específicos de isoformas PI3K :

Cellular Effect

Cell Line	Type	Value	Description	References
HCT-116	IC₅₀	0.2 μM Compound: 1, CH5132799	Antiproliferative activity against human HCT116 cells expressing PI3Kalpha H1047R mutant Antiproliferative activity against human HCT116 cells expressing PI3Kalpha H1047R mutant	[PMID: 21316229]
ME-180	IC₅₀	0.14 μM Compound: 1, CH5132799	Antiproliferative activity against human ME180 cells expressing PI3Kalpha E545K mutant Antiproliferative activity against human ME180 cells expressing PI3Kalpha E545K mutant	[PMID: 21316229]
MFE-280	IC₅₀	0.18 μM Compound: 1, CH5132799	Antiproliferative activity against human MFE280 cells expressing PI3Kalpha H1047Y mutant Antiproliferative activity against human MFE280 cells expressing PI3Kalpha H1047Y mutant	[PMID: 21316229]
SK-OV-3	IC₅₀	0.12 μM Compound: 1, CH5132799	Antiproliferative activity against human SKOV3 cells expressing PI3Kalpha H1047R mutant Antiproliferative activity against human SKOV3 cells expressing PI3Kalpha H1047R mutant	[PMID: 21316229]
T47D	IC₅₀	0.056 μM Compound: 1, CH5132799	Antiproliferative activity against human T47D cells expressing PI3Kalpha H1047R mutant Antiproliferative activity against human T47D cells expressing PI3Kalpha H1047R mutant	[PMID: 21316229]

In Vitro

Izorlisib (CH5132799) is a selective class I PI3K inhibitor with potent antitumor activity against tumors harboring the PIK3CA mutations. Izorlisib selectively inhibits class I PI3Ks and PI3Kα mutants in in vitro kinase assays. Izorlisib inhibits class I PI3Ks, particularly PI3Kα, with an IC₅₀ of 14 nM. IC₅₀ values against class II PI3Ks (C2α and C2β), a class III PI3K (Vps34), and a class IV PI3K (mTOR) are more than 100-fold higher than that against PI3Kα. Interestingly, slightly lower IC₅₀ values are observed against PI3Kα with oncogenic mutations E542K, E545K, and H1047R than against wild-type (WT) PI3Kα. In an analysis of cocrystal structure with PI3Kγ (PBD ID: 3APC), Izorlisib is shown to interact with ATP-binding sites of the enzyme, suggesting an ATP competitive mode of inhibition. No significant inhibitory activities of Izorlisib are observed against a representative panel of 26 protein kinases, including RTKs, nonreceptor tyrosine kinases, and serine/threonine kinases. These data indicate that Izorlisib is a selective class I PI3K inhibitor, especially against PI3Kα and its mutants. Izorlisib shows superior antiproliferative activity across the 4 tumor types, with 75% (45/60) of lines having an IC₅₀ below 1 μM and 38% (23/60) of lines having an IC₅₀ below 0.3 μM^[1].

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

In Vivo

Mice bearing BT-474 tumors (n=14) are orally administered 50 mg/kg of Everolimus on a daily basis for 31 days and then randomized. After randomization, the mice are orally administered 50 mg/kg of Everolimus (n=4) and 12.5 mg/kg (n=5), and 25 mg/kg (n=5) of Izorlisib on a daily basis for 7 days. C, the vehicle-, Everolimus, and CH5132799-treated (25 mg/kg) tumors are resected at 4 hours after terminal administration in B, lysed, and analyzed by Western blotting. Izorlisib administration leads to a remarkable regression in a dose-dependent manner of the tumors regrown after the long-term Everolimus treatment. The tumors are resected at the end of treatment and analyzed by Western blotting with respect to PI3K pathway inhibition. Izorlisib suppresses various effectors in the PI3K pathway, including Akt, FoxO1, S6K, S6, and 4E-BP1, whereas Everolimus inhibits only phosphorylation of S6K and S6, both downstream effectors of mTORC1^[1].

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

Ensayo clínico

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

Chemical Information

No. CAS 1007207-67-1
Appearance Solid
Peso molecular 377.42
Fòrmula C₁₅H₁₉N₇O₃S
Color White to gray
SMILES

NC1=NC=C(C2=C3C(N(S(=O)(C)=O)CC3)=NC(N4CCOCC4)=N2)C=N1
Synonyms

CH5132799
Envío

Room temperature in continental US; may vary elsewhere.

Almacenamiento

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (3)

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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
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
Sci Rep

QSAR analysis on a large and diverse set of potent phosphoinositide 3-kinase gamma (PI3Kγ) inhibitors using MLR and ANN methods. [Abstract]

2022 Apr 12;12(1):6090. PMID: 35414065

Solvente y solubilidad

In Vitro:

DMSO : 4.55 mg/mL (12.06 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

2.6496 mL

13.2478 mL

26.4957 mL

5 mM

0.5299 mL

2.6496 mL

5.2991 mL

10 mM

0.2650 mL

1.3248 mL

2.6496 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Calculadora de molaridad

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

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Calculadora de dilución

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

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 90% Corn Oil

Solubility: ≥ 0.46 mg/mL (1.22 mM); Clear solution

This protocol yields a clear solution of ≥ 0.46 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (4.6 mg/mL) to 900 μL Corn oil, 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

Protocolo

Cell Assay^[1]

The cell lines are added to the wells of 96-well plates containing 0.076 to 10,000 nM CH5132799 and incubated at 37°C. After 4 days of incubation, Cell Counting Kit-8 solution is added and, after incubation for several more hours, absorbance at 450 nm is measured with Microplate-Reader iMark. The antiproliferative activity is calculated. The IC₅₀ values are calculated^[1].

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

Animal Administration^[1]

Mice^[1]
Female BALB-nu/nu mice (CAnN.Cg-Foxn1/CrlCrlj nu/nu) are used. A total of 4×10⁶ to 1.2×10⁷ cells are suspended in 100 to 200 μL serum-free culture medium and injected subcutaneously into the right flank of the mice. Tumor size is measured by using a gauge twice per week, and tumor volume (TV) is calculated. Once the tumors reach a volume of approximately 200 to 300 mm³, animals are randomized into groups (n=4 or 5 in each group) and treatment is initiated. CH5132799 and Everolimus are orally administered once a day and Trastuzumab is intravenously injected once a week.

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

Pureza y Documentación

Select Batch:

Pureza: 99.98%

Assay: 99.98%

ee.: 99.98%

Ficha de datos (282 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)
Instrucciones de manejo (2659 KB)

Referencias

[1]. Tanaka H, et al. The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res, 2011, 17(10), 3272-3281. [Content Brief]

[2]. Ohwada J, et al. Discovery and biological activity of a novel class I PI3K inhibitor, CH5132799. Bioorg Med Chem Leff, 2011, 21(6), 1767-1772. [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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.6496 mL	13.2478 mL	26.4957 mL	66.2392 mL
	5 mM	0.5299 mL	2.6496 mL	5.2991 mL	13.2478 mL
	10 mM	0.2650 mL	1.3248 mL	2.6496 mL	6.6239 mL

Keywords

Izorlisib

3 Cited Publications

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Izorlisib

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Cancer Stem Cells Compound Library

Pain-Related Compound Library

Membrane Protein-targeted Compound Library

Highly Selective Inhibitors Library

Anti-Hematopathy Compound Library

Anti-Ovarian Cancer Compound Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Clinical Compound Library Plus

Bioactive Compound Library

Anti-Fibrosis Compound Library

Anti-Brain Cancer Compound Library

Cell Proliferation Compound Library

High-Throughput Bioactive Compound Library

Anti-Rheumatic Arthritis Compound Library

Posttranslational Modification Library

RNA Binding Bioactive Compound Library

Lactylation Compound Library

Publications Citing Use of MedChemExpress (MCE) Izorlisib

Ver todos los productos específicos de isoformas PI3K

Actividad biológica

Chemical Information

Publications (3)

Solvente y solubilidad

Protocolo

Pureza y Documentación

Referencias

Help & FAQs

Complete Stock Solution Preparation Table

Izorlisib Related Classifications

Referencia número: HY-15466