| Identification | Back Directory | [Name]
1-Piperazinedodecanamide, 4-[5-[(3,4-dihydro-4-oxo-1-phthalazinyl)methyl]-2-fluorobenzoyl]-N-[2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]ethyl]-λ-oxo- | [CAS]
2523016-96-6 | [Synonyms]
SK-575
1-Piperazinedodecanamide, 4-[5-[(3,4-dihydro-4-oxo-1-phthalazinyl)methyl]-2-fluorobenzoyl]-N-[2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]ethyl]-λ-oxo- | [Molecular Formula]
C47H53FN8O8 | [MOL File]
2523016-96-6.mol | [Molecular Weight]
876.99 |
| Chemical Properties | Back Directory | [density ]
1.40±0.1 g/cm3(Predicted) | [solubility ]
DMSO:87.7(Max Conc. mg/mL);100.0(Max Conc. mM) | [form ]
Solid | [pka]
10.74±0.40(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Description]
SK-575 is a Highly Potent and Efficacious Proteolysis-Targeting Chimera Degrader of PARP1 for Treating Cancers. SK-575 potently inhibits the growth of cancer cells bearing BRCA1/2 mutations and induces potent and specific degradation of PARP1 in various human cancer cells even at low picomolar concentrations. SK-575 achieves durable tumor growth inhibition in mice when used as a single agent or in combination with cytotoxic agents, such as temozolomide and cisplatin. | [Uses]
SK-575 is a highly potent and specific proteolysis-targeting chimera (PROTAC) degrader of PARP1, with an IC50 of 2.30 nM. SK-575 potently inhibits the growth of cancer cells bearing BRCA1/2 mutations[1]. | [in vivo]
SK-575 (mice bearing BRCA2-mutated Capan-1 xenografts, 25 and 50 mg/kg, IP, once daily for 5 days) significantly inhibits the tumor growth in vivo as a single-agent in HR-deficient xenograft models[1].
SK-575 (25 mg/kg, IP, once) achieves sufficient exposure in plasma for over 24 h and effectively induces PARP1 degradation in the SW620 xenograft tumor tissue with the effect persisting for >24 h[1].
| Animal Model: | Male BALB/c nude mice (bearing xenograft Capan-1 tumors)[1] | | Dosage: | 25 mg/kg, 50 mg/kg | | Administration: | IP, once daily for 5 consecutive days | | Result: | Inhibited tumor growth. SK-575 at these doses (25 and 50 mg/kg) were well tolerated, with no mice lethality or significant weight loss observed during the treatment time. |
| Animal Model: | Female ICR mice (20-23 g, 6-7 week-old, n=3 per group)[1] | | Dosage: | 25 mg/kg | | Administration: | Intraperitoneally, a single dose (Pharmacokinetic Analysis) | | Result: | Pharmacokinetic Parameters of SK-575 in female ICR mice[1].
| Parameters | mean | | Tmax (h) | 0.25 | | Cmax (ng/mL) | 1843 | | AUCall (ng/mL?h) | 5316 | | AUCinf (ng/mL?h) | 5363 | | t1/2 (ng/mL) | 3.08 |
|
| [IC 50]
PARP1: 2.30 nM (IC50) | [storage]
Store at -20°C | [References]
[1] Cao C, et al. Discovery of SK-575 as a Highly Potent and Efficacious Proteolysis-Targeting Chimera Degrader of PARP1 for Treating Cancers. J Med Chem. 2020 Oct 8;63(19):11012-11033. DOI:10.1021/acs.jmedchem.0c00821 |
|
|