PCSK9-IN-13

• CAT Number: I041976
• CAS Number: 2244129-23-3
• Molecular Formula: C30H33N5O2
• Molecular Weight: 495.62
• Purity: ≥95%
• Synonyms: N-[3-[[(3S)-3-aminopiperidin-1-yl]methyl]-5-(4-methylimidazol-1-yl)phenyl]-4-methyl-3-phenoxybenzamide
• InChI: InChI=1S/C30H33N5O2/c1-21-10-11-24(15-29(21)37-28-8-4-3-5-9-28)30(36)33-26-13-23(18-34-12-6-7-25(31)19-34)14-27(16-26)35-17-22(2)32-20-35/h3-5,8-11,13-17,20,25H,6-7,12,18-19,31H2,1-2H3,(H,33,36)/t25-/m0/s1
• InChIKey: SUNSLACFIOGRFF-VWLOTQADSA-N
• SMILES: CC1=C(C=C(C=C1)C(=O)NC2=CC(=CC(=C2)CN3CCCC(C3)N)N4C=C(N=C4)C)OC5=CC=CC=C5

PCSK9-IN-13(compound 3f) is a potent PCSK9 inhibitor, which can antagonize low-density lipoprotein (LDL) receptor binding by binding to PCSK9, with an IC50 of 537 nM[1].
PCSK9-IN-13(compound 3f) (0.1 or 1 μM) restores LDL uptake in HepG2 hepatocytes in a dose-dependent manner[1].
PCSK9-IN-13(compound 3f) (3.28 or 16.4 mg/kg/day, s.c., 14 days) in male C57BL/6 mice dose not show a reduction in total cholesterol at a dose of 3.28 mg/kg, however, a dose of 16.4 mg/kg shows a significant reduction of total cholesterol plasma levels by approximately 10%, and exhibits excellent bioavailability[1].
The pharmacokinetic parameters of PCSK9-IN-13(compound 3f) in C57BL/6 mice

Parameter
SC
PO
IV(single)
IV(cassette)

Dose(mg/kg)
20
20
5
0.4

Tmax(h)
1
2
–
–

Cmax(ng/mL)
2207
52.6
–
–

CL(L/h/kg)
–
–
1.09
0.3

Vss(L/kg)
–
–
3.87
9.13

T1/2(h)
5.47
–
9.86
25.7

AUC∞(h*ng/mL)
16811
–
4605
1472

MRT∞(h)
–
–
3.56
34.9

F(%)
91.3
0.527
–
–

Reference

[1]. Benny J. Evison, et al. A small molecule inhibitor of PCSK9 that antagonizes LDL receptor binding via interaction with a cryptic PCSK9 binding groove.Bioorganic & Medicinal Chemistry