CH5132799

SKU: orb1305260

Description

CH5132799

Research Area

Signal Transduction

Key Properties

• CAS Number: 1007207-67-1
• MW: 377.42
• Purity: 99.41%
• Formula: C₁₅H₁₉N₇O₃S
• SMILES: CS(=O)(=O)N1CCc2c1nc(nc2-c1cnc(N)nc1)N1CCOCC1
• Target: mTOR,PI3K
• Solubility: Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:1 mg/mL (2.65 mM)

Bioactivity

• Target IC50:
  PI3Kγ:36 nM|PI3Kα:14 nM|PI3Kβ:0.12 μM|PI3Kδ:0.50 μM
• In Vivo:
  CH5132799 effectively inhibits the phosphorylation of Akt and its direct substrates, including PRAS40 and FoxO1/3a, as well as downstream factors (such as S6K, S6, and 4E-BP1), in KPL-4 breast cancer cells harboring PIK3CA mutations. Cancer cell lines with PIK3CA mutations are notably sensitive to CH5132799, which demonstrates significant antiproliferative activity in human tumor cell lines with activated PI3K pathways due to mutations. CH5132799 selectively inhibits Class I PI3Ks with IC50 values of 0.014 μM for PI3Kα, 0.12 μM for PI3Kβ, 0.50 μM for PI3Kδ, and 0.036 μM for PI3Kγ, showing weaker inhibition of Class II and III PI3Ks and mTOR, and no inhibitory activity against 26 other protein kinases (IC50 > 10 μM). Compared to wild-type PI3Kα, CH5132799 exhibits stronger inhibitory activity against oncogenic mutants E542K (IC50 = 6.7 nM), E545K (IC50 = 6.7 nM), and H1047R (IC50 = 5.6 nM) of PI3Kα.
• In Vitro:
  CH5132799, used as a clinical backup, exhibits high oral bioavailability (101% in mice), stability in human liver microsomes, and in vivo antitumor activity. This compound displays favorable oral bioavailability across different species including mice, rats, monkeys, and dogs (F: 54.2-101%). In a heterotrophic transplant mouse model of human breast cancer (KPL-4: PI3Ka H1047R), oral treatment with CH5132799 (12.5 mg/kg, q.d.) demonstrated significant tumor reduction. Additionally, CH5132799 shows effective in vivo antitumor activity in various heterotrophic transplant models bearing different PIK3CA mutation loads.
• Cell Research:
  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 by the formula (1- T/C) × 100 (%), in which T and C represent absorbance at 450 nm of the cells treated with CH5132799 (T) and that of untreated control cells (C). The IC50 values are calculated by using Microsoft Excel 2007. (Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

CH5132799, CH-5132799, CH 5132799, lzorlisib, inhibit, Inhibitor, mTOR, PI3Kγ, PI3Kδ, PI3Kβ, PI3Kα, PI3K, Phosphoinositide 3-kinase

Compound Identifiers

PubChem CID

49784945