Venadaparib (IDX-1197; IDX1197) is a novel, selective and orally bioactive PARP inhibitor (IC50s = 1 ~2 nM) with anticancer activity. IDX-1197 converts SSBs into DSBs, or double-strand breaks, by blocking PARP, preventing cancer cells from repairing SSBs. IDX-1197 causes synthetic lethality, which is characterized by cell death brought on by simultaneous disruption of two genes without causing harm to healthy cells. Patients with homologous recombination deficiency (HRD) are the main target population for IDX-1197. The enzymes PARP1 and PARP2 are more successfully trapped on damaged DNA by IDX-1197, which is noteworthy for having a particularly strong trapping effect.

Physicochemical Properties

Molecular Formula	C23H23FN4O2
Molecular Weight	406.4527
Exact Mass	406.18
Elemental Analysis	C, 67.97; H, 5.70; F, 4.67; N, 13.78; O, 7.87
CAS #	1681017-83-3
Related CAS #	1681017-83-3; 1681020-60-9 (HCl)
PubChem CID	117955898
Appearance	White to yellow solid powder
LogP	2.3
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	6
Heavy Atom Count	30
Complexity	703
Defined Atom Stereocenter Count	0
InChi Key	YNBQAYKYNYRCCA-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H23FN4O2/c24-20-8-5-14(10-21-17-3-1-2-4-18(17)22(29)27-26-21)9-19(20)23(30)28-12-15(13-28)11-25-16-6-7-16/h1-5,8-9,15-16,25H,6-7,10-13H2,(H,27,29)
Chemical Name	4-[[3-[3-[(cyclopropylamino)methyl]azetidine-1-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one
Synonyms	Venadaparib; IDX1197; IDX 1197; IDX-1197
HS Tariff Code	2934.99.9001
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 ( IC50 = 1.4 nM ); PARP2 ( IC50 = 1 nM )
ln Vitro	IDX-1197 strongly and specifically inhibits PARP1-mediated PAR expression in DNA damage-induced Hela cells, and does so without being sensitive to PARP5A (Tankyrase-1). [1]
ln Vivo	IDX-1197 administered orally as opposed to the Olaparib treatment group, results in dose-dependently strong inhibition of tumor growth in the germline BRCA1-mutated ovarian cancer PDX model. This is demonstrated in tumor tissues.[1]
Animal Protocol	germline BRCA1-mutated ovarian cancer PDX model o.g.
References	[1]. Mol Cancer Ther (2018) 17 (1_Supplement): A106.
Additional Infomation	Venadaparib is an orally bioavailable inhibitor of the nuclear enzymes poly(ADP-ribose) polymerase (PARP) 1 and 2, with potential antineoplastic activity. Upon administration, venadaparib selectively binds to PARP-1 and -2 and prevents PARP-1 and -2 mediated DNA repair of single-strand DNA (ssDNA) breaks via the base-excision repair pathway. This promotes the conversion of ssDNA breaks to double-stranded DNA breaks, promotes genomic instability and eventually leads to apoptosis. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA and is activated by ssDNA breaks.

Solubility Data

Solubility (In Vitro)

DMSO: ~81 mg/mL (~199.3 mM) Ethanol: ~5 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5.75 mg/mL (14.15 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 57.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: ≥ 5 mg/mL (12.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 3: 5 mg/mL (12.30 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4603 mL	12.3016 mL	24.6033 mL
	5 mM	0.4921 mL	2.4603 mL	4.9207 mL
	10 mM	0.2460 mL	1.2302 mL	2.4603 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.