XIAP/cIAP1 antagonist-1 is a potent and orally active XIAP/cIAP1 antagonist with EC50s of 5.1 nM and 0.32 nM for XIAP and cIAP1, respectively. XIAP/cIAP1 antagonist-1 inhibits the tumor growth in dose-dependent manner in vivo[1].
in vivo
XIAP/cIAP1 antagonist-1 (compound 26) (7.5, 15, 30 mg/kg; p.o.; daily for 24 days) inhibits the tumor growth in dose-dependent manner[1].
XIAP/cIAP1 antagonist-1 (1 mg/kg for i.v.; 5, 30 mg/kg for p.o.) shows oral bioavailability (F=22%) at 5 mg/kg[1]. Pharmacokinetic Parameters of XIAP/cIAP1 antagonist-1 in Balb/c SCID mice[1].
dose (mg/kg)
route
Tmax (h)
Cmax (μg/mL)
CLp (mL/min/kg)
Vss (L/kg)
half life (h)
AUC (μg·h/mL)
F (%)
1
IV
40.9
6.4
3.0
0.41
5
PO
2
0.12
1.8
0.45
22
30
PO
1
1.7
12.1
Animal Model:
Balb/c SCID mice bearing MDA-MB-231 xenografts[1]
Dosage:
7.5, 15, 30 mg/kg
Administration:
PO; daily for 24 days
Result:
Inhibited the tumor growth in dose-dependent manner.
Animal Model:
Balb/c SCID mice bearing MDA-MB-231 xenografts[1]
Dosage:
Administration:
1 mg/kg for i.v.; 5, 30 mg/kg for p.o.
Result:
Showed oral bioavailability (F=22%).
IC 50
XIAP: 5.1 nM (IC50); cIAP1: 0.32 nM (IC50)
References
[1] Tamanini E, et al. Discovery of a Potent Nonpeptidomimetic, Small-Molecule Antagonist of Cellular Inhibitor of Apoptosis Protein 1 (cIAP1) and X-Linked Inhibitor of Apoptosis Protein (XIAP). J Med Chem. 2017; 60(11):4611-4625. DOI:10.1021/acs.jmedchem.6b01877
