TRPC6-IN-1

• CAT Number: I019925
• CAS Number: 901715-05-7
• Molecular Formula: C21H23FN4O3
• Molecular Weight: 398.43
• Purity: ≥95%
• Synonyms: ethyl 4-[3-(4-fluorophenyl)-2-methyl-7-oxo-1H-pyrazolo[1,5-a]pyrimidin-5-yl]piperidine-1-carboxylate
• InChI: InChI=1S/C21H23FN4O3/c1-3-29-21(28)25-10-8-14(9-11-25)17-12-18(27)26-20(23-17)19(13(2)24-26)15-4-6-16(22)7-5-15/h4-7,12,14,24H,3,8-11H2,1-2H3
• InChIKey: OXPMSNBGJOEGSC-UHFFFAOYSA-N
• SMILES: CCOC(=O)N1CCC(CC1)C2=CC(=O)N3C(=N2)C(=C(N3)C)C4=CC=C(C=C4)F

TRPC6-IN-1 is a Transient Receptor Potential Canonical 6 Channel (TRPC6) inhibitor, with an EC50 of 4.66 μM.
TRPC6-IN-1 (compound 4o) rises in the TRPC6 cells in a concentration dependent manner, with a mean EC50 value of 4.66±0.03 μM, demonstrating a comparable activity of the compound on TRPC6 as the original lead. TRPC6-IN-1 is also tested on HEK293 cells that co-expressed μ opioid receptor (MOR) and TRPC4β, which belongs to a different subgroup of TRPC channels than TRPC3/6/7. Upon stimulation by a μ agonist, these cells show a robust increase in [Ca2+]i. TRPC6-IN-1 also evokes whole-cell currents in HEK293 cells that express human TRPC3. TRPC6-IN-1 elicits concentration dependent current increases in the TRPC7 cells. Different from TRPC6, the currents show some desensitization in the high TRPC6-IN-1 concentrations (10 and 30 μM) at both negative and positive potentials even though the low Ca2+ (0.1 mM) bath solution is used. Nonetheless, a stepwise increase in the TRPC7 currents is still detected at <10 μM TRPC6-IN-1[1].

Reference

[1]. Qu C, et al. Pyrazolopyrimidines as Potent Stimulators for Transient Receptor Potential Canonical 3/6/7 Channels. J Med Chem. 2017 Jun 8;60(11):4680-4692.
 [Content Brief]