3-[(1s,4r)-4-(4-chlorobenzenesulfonyl)-4-(2,5-difluorophenyl)cyclohexyl]propanoic acid

• ChemBase ID: 73134
• Molecular Formular: C21H21ClF2O4S
• Molecular Mass: 442.9038464
• Monoisotopic Mass: 442.08171427
• SMILES: c1cc(ccc1Cl)S(=O)(=O)[C@]1(CC[C@H](CC1)CCC(=O)O)c1c(ccc(c1)F)F
• Canonical SMILES: OC(=O)CC[C@@H]1CC[C@](CC1)(c1cc(F)ccc1F)S(=O)(=O)c1ccc(cc1)Cl
• InChI: InChI=1S/C21H21ClF2O4S/c22-15-2-5-17(6-3-15)29(27,28)21(18-13-16(23)4-7-19(18)24)11-9-14(10-12-21)1-8-20(25)26/h2-7,13-14H,1,8-12H2,(H,25,26)/t14-,21+
• InChIKey: XCGJIFAKUZNNOR-QCKZDCLWSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 3-[(1s,4r)-4-(4-chlorobenzenesulfonyl)-4-(2,5-difluorophenyl)cyclohexyl]propanoic acid
• IUPAC Traditional name: 3-[(1s,4r)-4-(4-chlorobenzenesulfonyl)-4-(2,5-difluorophenyl)cyclohexyl]propanoic acid
• Synonyms: MK-0752

Database IDs

• CAS Number: 471905-41-6
• PubChem SID: 162038054
• PubChem CID: 9803433

CALCULATED PROPERTIES

• Acid pKa: 3.530204
• H Acceptors: 4
• H Donor: 1
• LogD (pH = 5.5): 3.500379
• LogD (pH = 7.4): 2.0968542
• Log P: 5.4629974
• Molar Refractivity: 105.9826 cm^3
• Polarizability: 41.7622 Å^3
• Polar Surface Area: 71.44 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: false

PROPERTIES

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: Y-secretase

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S2660

Biological Activity

• Description: MK-0752 is a moderately potent γ-secretase inhibitor, which reduces Aβ40 production with IC50 of 5 nM in human SH-SY5Y cells.
• Targets: γ-secretase
• IC50: 5 nM ^[1]
• In Vitro: MK-0752 is identified as a moderately potent γ-secretase inhibitor, which reduces Aβ40 in a dose-dependent manner with an IC50 of 5 nM in human SH-SY5Y cells. ^[1] In vitro, MK-0752 blocks Notch-intracellular domain (ICD) cleavage and its subsequent nuclear translocation. ^[2]
• In Vivo: MK-0752 (240 mg/kg) reduces the generation of newly produced Aβ with 90% decrease of AUV in the brain of rhesus monkeys. In addition, MK-0752 treatment increases levels of Aβ 1–14, Aβ 1–15, and Aβ 1–16 , while decreases levels of Aβ 1–17. ^[1] In guinea-pigs, oral administration of MK-0752 (10 mg/kg -30 mg/kg) results in the dose-dependent reduction of Aβ40 in plasma, brain and cerebrospinal fluid (CSF) with IC50 of 440 nM in brain. ^[2]
• Clinical Trials: MK-0752 study has been completed in Phase I clinical trials in patients with Metastatic or Locally Advanced Breast Cancer and Other Solid Tumors.
• Features: MK-0752 is a moderately potent γ-secretase inhibitor.

Combination Therapy

• Description: Combination of MK-0752 and Docetaxel is currently in Phase I/II clinical trials in patients with Locally Advanced or Metastatic Breast Cancer.

Protocol

• Protocol: Animal Study ^[1]
• Animal Models: Cisterna Magna Ported (CMP) Rhesus Monkey Model.
• Formulation: MK-0752 is dissolved in water.
• Doses: ≤240 mg/kg
• Administration: Administered via p.o.

References

• References: [1] Cook JJ, et al. J Neurosci, 2010, 30(19), 6743-6750.
• References: [2] Harrison H, et al. Cancer Res, 2010, 70(2), 709-718.

REFERENCES

• Cook JJ, et al. J Neurosci, 2010, 30(19), 6743-6750.
• Harrison H, et al. Cancer Res, 2010, 70(2), 709-718.