5-[3-(ethanesulfonyl)phenyl]-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide

• ChemBase ID: 73183
• Molecular Formular: C28H32N4O3S
• Molecular Mass: 504.64368
• Monoisotopic Mass: 504.2195119
• SMILES: C1N(CCC(C1)NC(=O)c1c(c2c(c(c1)c1cc(ccc1)S(=O)(=O)CC)c1c([nH]2)ncc(c1)C)C)C
• Canonical SMILES: CCS(=O)(=O)c1cccc(c1)c1cc(C(=O)NC2CCN(CC2)C)c(c2c1c1cc(C)cnc1[nH]2)C
• InChI: InChI=1S/C28H32N4O3S/c1-5-36(34,35)21-8-6-7-19(14-21)23-15-22(28(33)30-20-9-11-32(4)12-10-20)18(3)26-25(23)24-13-17(2)16-29-27(24)31-26/h6-8,13-16,20H,5,9-12H2,1-4H3,(H,29,31)(H,30,33)
• InChIKey: WKDACQVEJIVHMZ-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 5-[3-(ethanesulfonyl)phenyl]-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide
• IUPAC Traditional name: 5-[3-(ethanesulfonyl)phenyl]-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide
• Synonyms: TAK-901; 5-[3-(Ethylsulfonyl)phenyl]-3,8-dimethyl-N-(1-methyl-4-piperidinyl)-9H-pyrido[2,3-b]indole-7-carboxamide

Database IDs

• CAS Number: 934541-31-8
• PubChem SID: 162038103
• PubChem CID: 16124208

CALCULATED PROPERTIES

• Acid pKa: 13.719836
• H Acceptors: 5
• H Donor: 2
• LogD (pH = 5.5): 0.4505901
• LogD (pH = 7.4): 2.194152
• Log P: 3.3651717
• Molar Refractivity: 144.5819 cm^3
• Polarizability: 58.487545 Å^3
• Polar Surface Area: 95.16 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: false

PROPERTIES

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: Aurora

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S2718

Biological Activity

• Description: TAK-901 is a novel inhibitor of Aurora A and Aurora B with IC50 of 21 nM and 15 nM, respectively.
• Targets: Aurora A-TPX2; Aurora B-INCENP
• IC50: 21 nM; 15 nM ^[1]
• In Vitro: TAK-901 inhibits Aurora A-TPX2 and Aurora B-INCENP in tight binding, time-dependent manner. Dissociation of TAK-901 from Aurora B-INCENP is slow with at 1/2 of 920 minutes, and the affinity constant for TAK-901 binding to Aurora B-INCENP is determined to be 0.02 nM. TAK-901 induces inhibition of cell proliferation in cultured human cancer cell lines from different tissues with IC50s ranging from 40 to 500nM. Consistent with Aurora B inhibition, TAK-901 treatment produces polyploidy in human PC3 prostate cancer and HL60 acute myeloid leukemia cells as measured by immunofluorescence and flow cytometry. Examination of a broad panel of kinases reveals that multiple kinases, including FLT3, FGFR and the Src family kinases, are inhibited by TAK-901 with IC50 values similar to those for Aurora A and B. In cells, TAK-901 suppresses the Flt3 and FGFR2 autophosphorylation with IC50 values close to that of Aurora B as measured by cellular histone H3 phosphorylation, whereas the IC50s for inhibition of cellular Src and Bcr Abl are 20-fold weaker. In a panel of pathway specific reporter-based cell models, TAK-901 inhibits the NFkB and JAK/STAT pathways with submicromolar potency. ^[1]
• Clinical Trials: TAK-901 is now under the Phase 1 clinical trial for the dose escalation in subjects with advanced hematologic malignancies.

References

• References: [1] Pamela Farrell, et al, AACR, 2009, Abstract B270

Toronto Research Chemicals - T004920

A novel Aurora B kinase inhibitor with potential antineoplastic activity. It binds to and inhibits the activity of Aurora B, which may result in a decrease in the proliferation of tumor cells that overexpress Aurora B. Aurora B is a positive regulator of

REFERENCES

• Pamela Farrell, et al, AACR, 2009, Abstract B270