ChemicalBook CAS DataBase List 2523016-96-6

2523016-96-6

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
Molecular Formula	C47H53FN8O8
Molecular Weight	876.99
MOL File	2523016-96-6.mol

Chemical Properties

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

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
T_max (h)	0.25
C_max (ng/mL)	1843
AUC_all (ng/mL?h)	5316
AUC_inf (ng/mL?h)	5363
t_1/2 (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

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