| Identification | Back Directory | [Name]
AT-IAP | [CAS]
1403898-55-4 | [Synonyms]
AT-IAP
ATIAP,AT IAP
Ethanone, 1-[6-[(4-fluorophenyl)methyl]-2,3-dihydro-3,3-dimethyl-1H-pyrrolo[3,2-b]pyridin-1-yl]-2-[(2R,5R)-5-methyl-2-[[(3R)-3-methyl-4-morpholinyl]methyl]-1-piperazinyl]- | [Molecular Formula]
C29H40FN5O2 | [MOL File]
1403898-55-4.mol | [Molecular Weight]
509.66 |
| Chemical Properties | Back Directory | [Boiling point ]
678.3±55.0 °C(Predicted) | [density ]
1.138±0.06 g/cm3(Predicted) | [form ]
Solid | [pka]
8.87±0.60(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
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 |
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