4-dodecyl-N-(1,3,4-thiadiazol-2-yl)benzene-1-sulfonamide

• ChemBase编号: 72744
• 分子式: C20H31N3O2S2
• 平均质量: 409.60904
• 单一同位素质量: 409.18576925
• SMILES: c1c(ccc(c1)S(=O)(=O)Nc1nncs1)CCCCCCCCCCCC
• Canonical SMILES: CCCCCCCCCCCCc1ccc(cc1)S(=O)(=O)Nc1nncs1
• InChI: InChI=1S/C20H31N3O2S2/c1-2-3-4-5-6-7-8-9-10-11-12-18-13-15-19(16-14-18)27(24,25)23-20-22-21-17-26-20/h13-17H,2-12H2,1H3,(H,22,23)
• InChIKey: BYWWNRBKPCPJMG-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 4-dodecyl-N-(1,3,4-thiadiazol-2-yl)benzene-1-sulfonamide
• IUPAC传统名: 4-dodecyl-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide
• 别名: PHT427; PHT 427; PHT-427

登记号

• CAS号: 1191951-57-1
• PubChem SID: 162037665
• PubChem CID: 44240850

理论计算性质

• Acid pKa: 5.3585653
• 质子受体: 4
• 质子供体: 1
• LogD (pH = 5.5): 6.0100937
• LogD (pH = 7.4): 5.410317
• Log P: 6.323884
• 摩尔折射率: 113.3469 cm^3
• 极化性: 44.132595 Å^3
• 极化表面积: 71.95 Å^2
• 可自由旋转的化学键: 13
• 里宾斯基五规则: false

分子性质

理化性质

• 溶解度: DMSO

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: Akt; PDK

产品相关信息

• 成盐信息: Free Base

详细说明

Selleck Chemicals - S1556

Research Area

• Description: Cancer

Biological Activity

• Description: PHT-427 is a dual Akt and PDPK1 inhibitor with K_i of 2.7 μM and 5.2 μM, respectively.
• Targets: Akt; PDPK1
• IC50: 2.7 μM; 5.2 μM ^[1]
• In Vitro: PH-427 is a pleckstrin homology domain inhibitor to Akt/PDPK1. PH-427 significantly reduces phospho-Ser241-PDPK1 phospho-Thr308-Akt in PC-3 prostate cancer cells at 10 μM, which shows that PHT-427 could inhibit both Akt and PDKP1. PHT-427 also inhibits translocation of the Akt and PDKP1 PH domains in plasma membrane. ^[1] PHT-427 induces apoptosis and inhibits Akt phosphorylation with IC50 of 6.3 μM, which mainly on its Ser473 residue and less strongly on Thr308 residue without affecting total Akt protein expression. PHT-427 also shows antiproliferation in Panc-1 cells with IC50 of 65 μM. ^[2]
• In Vivo: PHT-427 shows great antitumor activity in BxPC-3 pancreatic, MCF-7 breast and A-549 NSCL cancer xenografts. PHT-427 gives up to an 80% inhibition of tumor growth in BxPC-3 at doses of 125 to 250 mg/kg. ^[1]

Combination Therapy

• Description: Combined with paclitaxel (10 mg/kg), PHT-427 (200 mg/kg) exhibits greater antitumor activity than both monotherapy in MCF-7 xenograft. Combined with erlotinib (50 mg/kg), PHT-427 (200 mg/kg) significantly inhibits tumor growth in NCI-H441 xenograft, which is negative to erlotinib. ^[1]

Protocol

• Protocol: Kinase Assay ^[1]
• Surface plasmon resonance (SPR) spectroscopy binding assays: All interaction analyses are performed with a Biacore 2000, Biacore 2000 Control Software v3.2, and BIAevaluation v4.1 analysis software. The PH domain GST-fusion proteins (Akt1, IRS1, and PDK1) are immobilized on a CM5 Sensorchip using Biacore’s Amine Coupling Kit to a level of 10,000 Response units (RUs). Small molecule analytes at concentrations ranging from 0.1 to 10 × the predicted KD are injected at a high flow rate (30μL/min). DMSO concentrations in all samples and running buffer are 1% (v/v) or less.
• Protocol: Cell Assay ^[2]
• Cell Lines: Panc-1 cells
• Concentrations: 1-50 μM
• Methods: Cell growth inhibition is determined using a micro-cytoxicity assay. Cells are plated in 96-well micro-cytoxicity at 5-10 × 10^3 cells per well (depending on cell doubling time) and grown for 7 days. PHT-427 dissolved in DMSO is added directly to the media, at various concentrations ranging from 1 to 50 μM. The endpoint is spectrophotometric determination of the protein content of each well using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. A concentration-response relationship at two or more concentration levels is used to obtain an IC50 for PHT-427.
• Protocol: Animal Study ^[1]
• Animal Models: BxPC-3, Panc-1, MiaPaCa-2, PC-3, SKOV-3, A-549 or MCF-7 cells are injected subcutaneously into the flanks of female scid mice.
• Formulation: 40 to 50 mg/mL in sesame seed oil
• Doses: 125-250 mg/kg
• Administration: Oral administration

References

• References: [1] Meuillet EJ, et al. Mol Cancer Ther, 2010, 9(3), 706-717.
• References: [2] Moses SA, et al. Cancer Res, 2009, 69(12), 5073-5081.

参考文献

• Meuillet EJ, et al. Mol Cancer Ther, 2010, 9(3), 706-717.
• Moses SA, et al. Cancer Res, 2009, 69(12), 5073-5081.