Izorlisib methanesulfonate
Based on 3 publication(s) in Google Scholar
Izorlisib (CH5132799) methanesulfonate is an orally active, selective Class I PI3K inhibitor with an IC50 value of 14 nM against PI3Kα. Izorlisib methanesulfonate specifically inhibits Class I PI3K (particularly PI3Kα and its mutants) and blocks the PI3K/Akt/mTOR pathway; this leads to cell cycle arrest at the G1 phase and apoptosis without triggering feedback activation of Akt by competitively binding to the ATP-binding site of PI3K. Izorlisib methanesulfonate can be used in research on cancers harboring PIK3CA mutations or PTEN loss (such as breast, ovarian, prostate, and endometrial cancers).
For research use only. We do not sell to patients.
- CAS No.: 2242053-82-1
- Formula: C16H23N7O6S2
- Molecular Weight:473.53
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Publications Citing Use of MedChemExpress (MCE) Izorlisib methanesulfonate
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Biological Activity
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PI3Kα 14 nM (IC50) |
PI3Kα-E542K 6.7 nM (IC50) |
PI3Kα-H1047R 5.6 nM (IC50) |
PI3Kβ 120 nM (IC50) |
PI3Kδ 36 nM (IC50) |
PI3Kγ 500 nM (IC50) |
Akt |
mTOR |
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Cell Line
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Type | Value | Description | References |
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| MFE-280 | IC50 |
0.18 μM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
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21316229 |
| HCT-116 | IC50 |
0.20 μM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
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21316229 |
| T47D | IC50 |
0.056 μM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
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21316229 |
| SK-OV-3 | IC50 |
0.12 μM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
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21316229 |
| ME-180 | IC50 |
0.14 μM
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Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
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21316229 |
Izorlisib (CH5132799) methanesulfonate demonstrates potent and selective inhibition of Class I PI3Ks in cell-free assays (IC50 values: 14 nM for PI3Kα, 6.7 nM for PI3Kα E542K, 5.6 nM for PI3Kα H1047R, 120 nM for PI3Kβ, 500 nM for PI3Kγ, and 36 nM for PI3Kδ) [1].
Izorlisib (1 nM-10 μM; 2 h) methanesulfonate inhibits PI3K/Akt/mTOR pathway signaling in KPL-4 and BT-474 cells [1].
Izorlisib (0.01 nM-10 μM; 24 h) methanesulfonate inhibits downstream PI3K signaling pathways in BT-474, SK-OV-3, MDA-MB-453, and HCT116 cells without inducing negative feedback activation of Akt [1].
Izorlisib (0.076 nM-10 μM; 4 days) methanesulfonate inhibits cell proliferation across 60 tumor cell lines, including those derived from breast, ovarian, prostate, and endometrial cancers [1].
Izorlisib (1 μM; 48 h) methanesulfonate induces G1 cell cycle arrest and apoptosis in KPL-4 cells [1].
Izorlisib methanesulfonate inhibites the proliferation of HCT116 (IC50 = 0.20 μM), KPL-4 (IC50 = 0.032 μM), T-47D (IC50 = 0.056 μM), SK-OV-3 (IC50 = 0.12 μM), MFE-280 (IC50 = 0.18 μM), and ME-180 (IC50 = 0.14 μM) cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:KPL-4 cells, BT-474 cells
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Concentration:0.001, 0.01, 0.1, 1, 10 μM
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Incubation Time:2 h
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Result:Suppressed the phosphorylation of Akt (S473, T308), PRAS40, S6K, S6, 4E-BP1, FoxO1, and FoxO3a.
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Cell Line:BT-474, SK-OV-3, MDA-MB-453, HCT116 cells
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Concentration:0.01 nM, 0.1 nM, 1 nM, 0.01 μM, 0.1 μM, 1 μM, 10 μM
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Incubation Time:24 h
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Result:Inhibited the phosphorylation of Akt, S6K, and 4E-BP1, and did not induce feedback activation of Akt.
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Cell Line:60 human tumor cell lines including breast, ovarian, prostate, and endometrial cancers
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Concentration:0.076 nM, 0.76 nM, 7.6 nM, 76 nM, 760 nM, 10 μM
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Incubation Time:4 days
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Result:Inhibited cell proliferation; cell lines harboring PIK3CA mutations showed higher drug sensitivity.
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Cell Line:KPL-4
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Concentration:1 μM
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Incubation Time:48 h
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Result:Induced cell cycle arrest in the G1 phase and increased the proportion of the sub-G1 (apoptotic) cell population.
Izorlisib (12.5 mg/kg; p.o.; single dose; 0.5-24 h treatment) methanesulfonate inhibits the phosphorylation of Akt and its downstream pathway proteins in a time-dependent manner in KPL-4 and BT-474 breast cancer mouse xenograft models[1].
Izorlisib (3.13-25 mg/kg; p.o.; once daily; >28 days) methanesulfonate exhibits potent tumor growth inhibition and regression activity in mouse xenograft models of ovarian cancer (SK-OV-3), endometrial cancer (MFE-280), PTEN-deficient gastric cancer (GXF97), prostate cancer (PC-3), and KRAS-mutant colorectal cancer (HCT116)[1].
Izorlisib (12.5 mg/kg; p.o.; once daily; 12 consecutive days) methanesulfonate shows synergistic anti-tumor activity when combined with Trastuzumab (HY-P9907) in a Trastuzumab-insensitive KPL-4 breast cancer mouse xenograft model, leading to complete tumor regression[1].
Izorlisib (12.5 mg/kg and 25 mg/kg; p.o.; once daily; 7-day continuous treatment) methanesulfonate demonstrates potent regression of drug-resistant tumors and inhibition of the PI3K/mTOR signaling pathway in a BT-474 breast cancer mouse xenograft model that relapsed after long-term everolimus (HY-10218) treatment[1].
Izorlisib (25 mg/kg; p.o.; once daily; 11 days) methanesulfonate inhibits tumor growth in a human prostate cancer PC-3 mouse xenograft model[2].
Izorlisib (12.5 mg/kg; p.o.; once daily; 2 weeks on/1 week off or 5 days on/2 days off; 6 weeks) methanesulfonate induces potent tumor regression in a human breast cancer KPL-4 mouse xenograft model[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB-nu/nu mice (female) were were injected subcutaneously into the right flank with 4 × 106 to 1.2 × 107 with KPL-4 and BT-474 cells[1]
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Dosage:0.39, 0.78, 1.56, 3.13, 6.25, 12.5, 25 mg/kg
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Administration:p.o.; once daily; 11-13 days
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Result:Significantly reduced tumor volume, particularly inducing rapid tumor regression in high-dose groups.
Reduced tumor cell proliferation and induced apoptosis.
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Animal Model:BALB-nu/nu mice (female) were were injected subcutaneously into the right flank with 4 × 106 to 1.2 × 107 with KPL-4 and BT-474 cells[1]
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Dosage:12.5 mg/kg
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Administration:p.o.; single dose; treated for 0.5, 1, 2, 4, 7, 24 h
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Result:Had a time-dependent inhibitory effect on the phosphorylation of Akt and its downstream pathway proteins.
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Animal Model:BALB-nu/nu mice (female) were were injected subcutaneously into the right flank with 4 × 106 to 1.2 × 107 with SK-OV-3 (ovarian), MFE-280 (endometrial), PTEN-deleted GXF97 (gastric), PC-3 (prostate), and KRAS-mutant HCT116 (colorectal) cells[1]
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Dosage:3.13, 6.25, 12.5, 25 mg/kg
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Administration:p.o.; once daily; more than 28 days
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Result:Potently inhibited tumor growth and promoted tumor regression
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Animal Model:BALB-nu/nu mice (female) were were injected subcutaneously into the right flank with 4 × 106 to 1.2 × 107 with BT-474 cells[1]
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Dosage:12.5 mg/kg
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Administration:p.o.; once daily; 12 consecutive days of treatment; Trastuzumab (30 mg/kg) was intravenously injected once a week for 2 weeks
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Result:Overcame resistance to Trastuzumab monotherapy and generated significant synergistic antitumor activity when used in combination.
Resulted in complete disappearance of the tumors, and this disappearance was maintained throughout a follow-up period of over 1 month without any additional administration.
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Animal Model:BALB-nu/nu mice (female) were were injected subcutaneously into the right flank with 4 × 106 to 1.2 × 107 with BT-474 cells[1]
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Dosage:12.5 mg/kg, 25 mg/kg
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Administration:p.o.; once daily; 7-day continuous treatment
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Result:Induced a dose-dependent and remarkable regression of tumors that had regrown after long-term everolimus treatment.
Inhibited various effector proteins in the PI3K/mTOR pathway (including the phosphorylation of 4E-BP1) and did not induce the feedback activation of Akt and FoxO1 that is typically caused by everolimus.
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Animal Model:Human prostate cancer PC-3 xenograft model[2]
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Dosage:25 mg/kg
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Administration:p.o.; once daily; for 11 days
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Result:Significantly inhibited tumor growth, achieving a tumor growth inhibition (TGI) rate of 101%.
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Animal Model:Human breast cancer KPL-4 xenograft model[2]
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Dosage:12.5 mg/kg
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Administration:p.o.; once daily; 2 weeks on/1 week off, 5 days on/2 days off; treatment started 25 days after tumor implantation and lasted for 6 weeks
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Result:Induced strong tumor regression.
The strong tumor regression was maintained even in the intermittent dosing schedules.
Chemical Information
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CAS No. 2242053-82-1
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Molecular Weight 473.53
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Formula C16H23N7O6S2
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SMILES
NC1=NC=C(C2=C3C(N(S(=O)(C)=O)CC3)=NC(N4CCOCC4)=N2)C=N1.CS(=O)(O)=O
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Synonyms
CH5132799 methanesulfonate
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications (3)
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Journal Impact Factor
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Most Recent
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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
Purity & Documentation
References
[1]. Tanaka H, et al. The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res. 2011 May 15;17(10):3272-81. [Content Brief]
[2]. Ohwada J, et al. Discovery and biological activity of a novel class I PI3K inhibitor, CH5132799. Bioorg Med Chem Lett. 2011 Mar 15;21(6):1767-72. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Izorlisib methanesulfonate Related Classifications
HY-15466A Related Classifications
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