4-[(1R)-1-aminoethyl]-N-(pyridin-4-yl)cyclohexane-1-carboxamide

• ChemBase ID: 72480
• Molecular Formular: C14H21N3O
• Molecular Mass: 247.33604
• Monoisotopic Mass: 247.16846231
• SMILES: n1ccc(cc1)NC(=O)C1CC[C@@H](CC1)[C@@H](C)N
• Canonical SMILES: C[C@H]([C@@H]1CCC(CC1)C(=O)Nc1ccncc1)N
• InChI: InChI=1S/C14H21N3O/c1-10(15)11-2-4-12(5-3-11)14(18)17-13-6-8-16-9-7-13/h6-12H,2-5,15H2,1H3,(H,16,17,18)/t10-,11-,12?/m1/s1
• InChIKey: IYOZTVGMEWJPKR-XFKKCKKNSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-[(1R)-1-aminoethyl]-N-(pyridin-4-yl)cyclohexane-1-carboxamide
• IUPAC Traditional name: 4-[(1R)-1-aminoethyl]-N-(pyridin-4-yl)cyclohexane-1-carboxamide
• Synonyms: Y-27632

Database IDs

• CAS Number: 146986-50-7
• PubChem SID: 162037405
• PubChem CID: 448042

CALCULATED PROPERTIES

• Acid pKa: 13.44126
• H Acceptors: 3
• H Donor: 2
• LogD (pH = 5.5): -2.010109
• LogD (pH = 7.4): -1.4054664
• Log P: 1.3447734
• Molar Refractivity: 72.4429 cm^3
• Polarizability: 27.996195 Å^3
• Polar Surface Area: 68.01 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: ROCK

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S1049

Research Area

• Description: Cancer

Biological Activity

• Description: Y-27632 2HCl is a selective ROCK1 (p160ROCK) inhibitor with K_i of 140 nM.
• Targets: ROCK1
• IC50: 140 nM (K_i) ^[1]
• In Vitro: Y-27632 2HCl inhibits ROCK-II while displaying little activity against PKC, cAMP-dependent protein kinase and myosin light-chain kinase (MLCK) with K_i of 26 μM, 25 μM and > 250 μM, respectively, as well as PKA activated by another Rho-family GTPase member, Cdc42. Y-27632 2HCl inhibits smooth-muscle contraction induces by various agonists including phenylephrine, histamine, acetylcholine, serotonin, endothelin, and thromboxane with IC50 of 0.3-1 μM, by selectively inhibiting Ca^2+ sensitization. Y-27632 2HCl suppresses Rho-induced, p160ROCK-mediated formation of stress fibres in cultured cells. ^[1] Y-27632 2HCl treatment blocks both Rho-mediated activation of actomyosin and LPA-stimulated invasive activity of MM1 cells in a concentration-dependent manner. ^[2] Y-27632 2HCl treatment is not only sufficient to initiate formation of exuberant axonal processes but also facilitates axonal maturation during the very early stages of axonogenesis, while largely sparing axon elongation. ^[3] In human embryonic stem (hES) cells, Y-27632 2HCl treatment at 10 μM markedly diminishes dissociation-induced apoptosis even in serum-free suspension (SFEB) culture, increases cloning efficiency (from ~1% to ~27%), facilitates subcloning after gene transfer, and enables SFEB-cultured hES cells to survive and differentiate into Bf1^+ cortical and basal telencephalic progenitors. ^[4]
• In Vivo: Oral administration of Y-27632 2HCl at 30 mg/kg significantly decreases the blood pressure in a dose-dependent manner in spontaneous hypertensive rats, renal hypertensive rats, as well as deoxycorticosterone acetate (DOCA)-salt hypertensive rats. ^[1] When Y-27632 2HCl is continuously administered at a rate of 0.55 μL per hour by implanted pumps for 11 days tumor cell invasion (MM1 cells expressing Val14-RhoA in rats) is significantly delayed. ^[2] By inhibiting ROCK, Y-27632 2HCl treatment attenuates hypoxia-induced angiogenesis and vascular remodeling in the pulmonary circulation. ^[5]

Protocol

• Protocol: Kinase Assay ^[1]
• Phosphorylation reactions: The p160ROCK is expressed in COS cells as tagged full-length proteins, and immunoprecipitated by the use of anti-tag antibodies. The p160ROCK (30 ng) is incubated with 40 μM [γ-^32P]ATP (3.3 Ci/mmol) and with 3 μg of either histone (HF2A), dephosphorylated casein or MBP in the presence of various concentrations of Y-27632 2HCl at 30 °C in a total volume of 31 μL. A 7 μL aliquot is taken at 0, 5, 10, and 20 minutes, mixed with an equal volume of 2 × Laemmli sample buffer, and applied to SDS-PAGE. The gel is stained with Commassie Blue, dried and subjected to analysis by a Bioimage Analyzer BAS2000. The Y-27632 2HCl concentration required to inhibit p160ROCK activity by 50% (IC50 value) is obtained. K_i value is calculated according to the equation, K_i = IC50/(1 + S/K_m), where S and K_m represent concentrations of and K_m value for ATP.
• Protocol: Animal Study ^[1]
• Animal Models: Male Wistar rats with spontaneous or induced hypertension
• Formulation: Dissolved in DMSO, and diluted in saline
• Doses: 30 mg/kg/day
• Administration: Orally

References

• References: [1] Uehata M, et al. Nature, 1997, 389(6654), 990-994.
• References: [2] Itoh K, et al. Nat Med, 1999, 5(2), 221-225.
• References: [3] Bito H, et al. Neuron, 2000, 26(2), 431-441.
• References: [4] Watanabe K, et al. Nat Biotechnol, 2007, 25(6), 681-686.
• References: [5] Hyvelin JM, et al. Circ Res, 2005, 97(2), 185-191.

REFERENCES

• Uehata M, et al. Nature, 1997, 389(6654), 990-994.
• Itoh K, et al. Nat Med, 1999, 5(2), 221-225.
• Watanabe K, et al. Nat Biotechnol, 2007, 25(6), 681-686.
• Hyvelin JM, et al. Circ Res, 2005, 97(2), 185-191.
• Bito H, et al. Neuron, 2000, 26(2), 431-441.