N-benzyl-2-[(pyrimidin-4-yl)amino]-1,3-thiazole-4-carboxamide

• ChemBase ID: 72690
• Molecular Formular: C15H13N5OS
• Molecular Mass: 311.36162
• Monoisotopic Mass: 311.08408106
• SMILES: c1(scc(n1)C(=O)NCc1ccccc1)Nc1ccncn1
• Canonical SMILES: O=C(c1csc(n1)Nc1ccncn1)NCc1ccccc1
• InChI: InChI=1S/C15H13N5OS/c21-14(17-8-11-4-2-1-3-5-11)12-9-22-15(19-12)20-13-6-7-16-10-18-13/h1-7,9-10H,8H2,(H,17,21)(H,16,18,19,20)
• InChIKey: DOBKQCZBPPCLEG-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-benzyl-2-[(pyrimidin-4-yl)amino]-1,3-thiazole-4-carboxamide
• IUPAC Traditional name: N-benzyl-2-(pyrimidin-4-ylamino)-1,3-thiazole-4-carboxamide
• Synonyms: Thiazovivin

Database IDs

• CAS Number: 1226056-71-8
• PubChem SID: 162037611
• PubChem CID: 46209426

CALCULATED PROPERTIES

• Acid pKa: 8.739566
• H Acceptors: 5
• H Donor: 2
• LogD (pH = 5.5): 2.5955677
• LogD (pH = 7.4): 2.5926514
• Log P: 2.6118014
• Molar Refractivity: 84.4194 cm^3
• Polarizability: 31.350014 Å^3
• Polar Surface Area: 79.8 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

PROPERTIES

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: ROCK

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S1459

Research Area

• Description: Cancer

Biological Activity

• Description: Thiazovivin (Tzv) is a novel ROCK inhibitor with IC50 of ~0.5 μM.
• Targets: ROCK
• IC50: ~0.5 μM ^[1]
• In Vitro: Although displaying little impact on cell proliferation, Thiazovivin treatment significantly enhances the survival of human embryonic stem cells (hESCs) after enzymatic dissociation more than 30-fold, while homogenously maintaining pluripotency with the characteristic colony morphology, expression of typical pluripotency markers such as alkaline phosphatase (ALP), and normal karyotype. Dissociated hESCs treated with Thiazovivin display dramatically increased adhesion to matrigel- or laminin-coated plates but not to gelatin-coated plates within a few hours. Thiazovivin treatment increases cell-ECM adhesion-mediated β1 integrin activity, which synergizes with growth factors to promote cell survival. In addition to activating integrin, Thiazovivin but not Tyrintegin (Ptn) protects hESCs from death in the absence of ECM in suspension through E-cadherin-mediated cell-cell interaction. Thiazovivin treatment potently inhibits endocytosis of E-cadherin, consequently stabilizing E-cadherin on the cell surface and leading to reestablishment of cell-cell interaction, which is essential for hESC survival in ECM-free conditions. Thiazovivin but not Tyrintegin (Ptn) at 2 μM inhibits Rho-associated kinase (ROCK) activity and protects hESCs at a similar level as the widely used selective ROCK inhibitor Y-27632 at 10 μM, suggesting that Rho-ROCK signaling regulates cell-ECM and cell-cell adhesion. ^[1] Thiazovivin at 1 μM increases the reprogramming efficiency of CB mononuclear cells to induced pluripotent stem cells (iPSCs) by more than 10 times. ^[3]

Combination Therapy

• Description: Thiazovivin (0.5 μM) in combination with ALK5 (TGFβ receptor) inhibitor SB 431542 (2 μM) and MEK inhibitor PD 0325901 (0.5 μM) greatly enhances the efficiency of fibroblast reprogramming to generate induced pluripotent stem cells (iPSCs), with a more than 200-fold improvement in reprogramming efficiency over the no-compound treatment and a 2-fold increase over the SB 431542 and PD 0325901 treatment. Addition of Thiazovivin to the cocktail of SB431542 and PD0325901 also improves the survival of iPSCs after splitting by trypsinization. ^[2]

Protocol

• Protocol: Kinase Assay ^[1]
• In vitro ROCK assay: Thiazovivin is dissolved in DMSO. CycLex Rho-kinase assay kit is used to detect ROCK activity using recombinant ROCK in the presence of increasing concentrations of Thiazovivin (~10 μM).

References

• References: [1] Xu Y, et al. Proc Natl Acad Sci U S A, 2010, 107(18), 8129-8134.
• References: [2] Lin T, et al. Nat Methods, 2009, 6(11), 805-808.
• References: [3] Hu K, et al. Blood, 2011, 117(14), e109-119.

REFERENCES

• Xu Y, et al. Proc Natl Acad Sci U S A, 2010, 107(18), 8129-8134.
• Lin T, et al. Nat Methods, 2009, 6(11), 805-808.
• Hu K, et al. Blood, 2011, 117(14), e109-119.