| Chemical Properties | Back Directory | [Boiling point ]
718.3±60.0 °C(Predicted) | [density ]
1.53±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
Soluble in DMSO | [pka]
4.21±0.10(Predicted) |
| Hazard Information | Back Directory | [Description]
BI-0252 is a potent, highly selective, orally active MDM2-p53 interaction inhibitor. | [Uses]
BI-0252 is an orally active, selective MDM2-p53 inhibitor with an IC50 of 4 nM. BI-0252 can induce tumor regressions in all animals of a mouse SJSA-1 xenograft, with concomitant induction of the tumor protein p53 (TP53) target genes and markers of apoptosis[1]. | [in vivo]
BI-0252 (orally; 25 mg/kg/day for 13 days and 100 mg/kg for 24 h) leads to time-dependent mRNA induction of TP53 target genes including CDKN1a, MDM2, and BBC3[1].
BI-0252 (iv and po; an iv dose of 5 mg/kg and a po dose of 50 mg/kg) showes low clearance in vivo after iv administration and high clearance after po administration. BI-0252 has high po in vivo exposure and good cellular potency[1].
| Animal Model: | Nude mice bearing established subcutaneous SJSA-1 tumors[1] | | Dosage: | 25 mg/kg/day or a single dose of 100 mg/kg | | Administration: | Orally; 25 mg/kg/day for 13 days and 100 mg/kg for 24 hours | | Result: | Leaded to time-dependent mRNA induction of TP53 target genes.
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| Animal Model: | Nontumor-bearing female NMRI nude mice[1] | | Dosage: | An iv dose of 5 mg/kg and a po dose of 50 mg/kg | | Administration: | Iv and po | | Result: | Showed low clearance in vivo after iv administration and high clearance after po administration.
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| [storage]
Store at -20°C | [References]
[1] Gollner A, et al. Discovery of Novel Spiro[[3]H-indole-3,2'-pyrrolidin]-2(1H)-one Compounds as Chemically Stable and Orally Active Inhibitors of the MDM2-p53 Interaction. J Med Chem. 2016 Nov 23;59(22):10147-10162. DOI:10.1021/acs.jmedchem.6b00900 |
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