PROTAC PARP1 degrader-4 (Compound 180055) is a selective PARP1 PROTAC degrader (DC50 in T47D and MDA-MB-231 cell lines is 180 nM and 240 nM, respectively). PROTAC PARP1 degrader-4 promotes the ubiquitination and degradation of PARP1 and inhibits the activity of PARP1 enzyme without producing a significant DNA trapping effect. PROTAC PARP1 degrader-4 can inhibit tumors carrying BRCA gene mutations while having little effect on the growth of normal cells (pink: PARP1 ligand; blue: E3 ligase VHL ligand; black: linker).

Physicochemical Properties

Molecular Formula	C51H62FN7O6S
Molecular Weight	920.14
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	PARP1
ln Vitro	PROTAC PARP1 degrader-4 (1-10 μM, 24-48 h) protects T47D and MOLT4 cells from genotoxicity-induced cell death[1]. The PROTAC PARP1 degrader-4 (10 μM, 3-6 days) induces cytotoxicity in BRCA1 mutant MOLT4 cells [1].
ln Vivo	PROTAC PARP1 degrader-4 (40 mg/kg, intraperitoneal injection, 16 days) has antitumor effects in BRCA1 mutant MOLT4 xenograft mice[1].
Cell Assay	Cell Viability Assay[1] Cell Types: Cardiomyocyte Cell Typess lacking BRCA1 mutations and MOLT4 cells Tested Tested Concentrations: 1, 5, 10 μM Incubation Duration: 144 h Experimental Results: Showed minimal cytotoxicity in cardiomyocyte Cell Typess lacking BRCA1 mutations. Induced substantial cytotoxic effects in MOLT4 cells with BRCA1 mutation.
Animal Protocol	Animal/Disease Models: 5-week-old NSG mice (injected 8 × 106 MOLT4 cells or 4 × 106 A2780)[1] Doses: 40 mg/kg Route of Administration: Intraperitoneal injection (i.p.), 16 days Experimental Results: Exhibited a noticeable reduction in tumor size compared to the control group. Effectively degraded PARP1 in tumors derived from MOLT4-xenografted mice. Showed no significant alterations in neutrophil count, lymphocyte count or glutamic-pyruvic transaminase levels.
References	[1]. Minimizing DNA trapping while maintaining activity inhibition via selective PARP1 degrader. Cell Death Dis. 2024 Dec 18;15(12):898.

Solubility Data

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.0868 mL	5.4340 mL	10.8679 mL
	5 mM	0.2174 mL	1.0868 mL	2.1736 mL
	10 mM	0.1087 mL	0.5434 mL	1.0868 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.