Antitumor agent-81

• CAT Number: I042581
• CAS Number: 2765180-17-2
• Molecular Formula: C19H19N7O3
• Molecular Weight: 393.40
• Purity: ≥95%
• Synonyms: 6-[1-(3,4,5-trimethoxyphenyl)triazol-4-yl]quinazoline-2,4-diamine
• InChI: InChI=1S/C19H19N7O3/c1-27-15-7-11(8-16(28-2)17(15)29-3)26-9-14(24-25-26)10-4-5-13-12(6-10)18(20)23-19(21)22-13/h4-9H,1-3H3,(H4,20,21,22,23)
• InChIKey: SWULRQWLALOGFO-UHFFFAOYSA-N
• SMILES: COC1=CC(=CC(=C1OC)OC)N2C=C(N=N2)C3=CC4=C(C=C3)N=C(N=C4N)N

Antitumor agent-81 (compound 5a) is a low cytotoxic P62-RNF168 agonist that promotes the interaction of P62 with RNF168. Antitumor agent-81 induces a decrease in RNF168-mediated H2A ubiquitination and impairs homologous recombination-mediated DNA repair. Antitumor agent-81 also inhibits mice xenograft tumor growth in a dose-dependent manner[1].
Antitumor agent-81 (0-20 µM; 72 h) exhibits antiproliferative activity in cells of the most common cancer types[1].
Antitumor agent-81 (1, 2, 5 µM; 24 h) compromises HR (homologous recombination)-mediated DSB repair in HCT-116 cells[1].
Antitumor agent-81 tethers the interaction between P62 and RNF168 in HCT-116 cells[1].
Antitumor agent-81 inhibits the catalytic activity of RNF168 and RNF168 E3 ligase activity in HCT-116 cells[1].
Antitumor agent-81 (5, 10 mg/kg; i.p.; single every 3 days for 22 days) suppresses tumor volumes in a dose-dependent manner in mice[1].

1.19

Pharmacokinetic Parameters of Antitumor agent-81 in Female BALB/c nude mice[1].

Dose
T1/2 (h)
Cmax (ng/mL)
AUC0-t (hng/mL)
CL ((mL/h)/kg)

IP (5 mg/kg)
16.17
26.10
215.69
19647.83

IP (10 mg/kg)
31.00
39.87
408.18
16554.30

IP (20 mg/kg)
22.10
52.23
1003.58
14669.81

Reference

[1]. Wang FC, et al. A 1,2,3-Triazole Derivative of Quinazoline Exhibits Antitumor Activity by Tethering RNF168 to SQSTM1/P62. J Med Chem. 2022 Nov 4.
 [Content Brief]