Home PI3K/Akt/mTOR PI3K inhibitor Serabelisib (TAK-117)

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Serabelisib (TAK-117) PI3K inhibitor

Cat.No.S8581

Serabelisib (TAK-117, INK-1117, MLN-1117) is a potent and selective oral PI3Kα isoform inhibitor (IC50 of 21 nmol/L against PI3Kα). It has demonstrated > 100-fold selectivity relative to other class I PI3K family members (PI3Kβ/γ/δ) and mTOR, and a high degree of selectivity against many other kinase.
Serabelisib (TAK-117) PI3K inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 363.37

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Quality Control

Batch: S858101 DMSO]4 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 99.86%
99.86

Chemical Information, Storage & Stability

Molecular Weight 363.37 Formula

C19H17N5O3

 Storage (From the date of receipt)
CAS No. 1268454-23-4 Download SDF Storage of Stock Solutions

Synonyms INK-1117, MLN-1117 Smiles C1COCCN1C(=O)C2=CN=C3N2C=C(C=C3)C4=CC5=C(C=C4)OC(=N5)N

Solubility

In vitro
Batch:

DMSO : 4 mg/mL (11.0 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Mechanism of Action

Targets/IC50/Ki
PI3Kα [1]
(Cell-free assay)
21 nM
In vitro
Serabelisib (TAK-117) administration in PIK3CA-mutant tumor cell lines results in potent PI3K pathway inhibition, blockade of cellular proliferation, and apoptosis[1]. This compound potently inhibits PI3K and demonstrates a greater than 100-fold selectivity relative to other class I PI3K family members and mTOR as well as a high degree of selectivity against a large panel of protein kinases. It blocks proliferation of tumor cell lines bearing PIK3CA mutations, and inhibits cellular phosphorylation and activity of AKT. However, it shows much less activity in PTEN-deficient tumor cells, which typically display constitutive PI3K pathway activation independent of PI3Kα[3].
In vivo
Serabelisib (TAK-117) administration leads to dose-dependent inhibition of tumor growth in murine xenograft models of human cancer (e.g., breast carcinoma) bearing PIK3CA oncogenic mutations, with corresponding inhibition of PI3K pharmacodynamic markers in tumor tissue. Preclinical antitumor activity of this compound as a single agent has been shown to be independent of dosing schedules and driven by total plasma exposures. Conversely, it is not efficacious in tumor models harboring PTEN and/or KRAS mutations. Preclinical studies show TAK-117 to have low potential for disrupting glucose metabolism or for causing cardiac adverse events; in rats and monkeys, doses up to 50 mg/kg/day were well tolerated. In human, the mean terminal half-life is approximately 11 hours (range, 6-14 hours). There is no meaningful accumulation with repeated dosing for any schedule[1]. Additionally, INK1117 does not significantly impair B and T cell function in vitro and in vivo[3].
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02625259 Completed
Neoplasm Advanced or Metastatic
Millennium Pharmaceuticals Inc.|Takeda
 January 8 2016 Phase 1
NCT02393209 Terminated
Non-small Cell Lung Cancer
Millennium Pharmaceuticals Inc.|Takeda
 June 3 2015 Phase 1|Phase 2
NCT01899053 Completed
Advanced Nonhematologic Malignancies
Millennium Pharmaceuticals Inc.|Takeda
 June 28 2013 Phase 1
NCT01449370 Completed
Metastatic Solid Tumors
Millennium Pharmaceuticals Inc.|Takeda
 October 2011 Phase 1

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