| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
PARP1 ( IC50 = 1.4 nM ); PARP2 ( IC50 = 1 nM )
Venadaparib targets the nuclear enzymes poly(ADP-ribose) polymerase 1 (PARP1) and 2 (PARP2), which are involved in DNA repair. PARP1 and PARP2 detect DNA single-strand breaks and catalyze the addition of poly(ADP-ribose) chains to target proteins, facilitating the recruitment of DNA repair proteins to the site of damage. By inhibiting PARP1 and PARP2, venadaparib prevents the repair of DNA single-strand breaks via the base-excision repair pathway. In cancer cells with BRCA mutations or other defects in homologous recombination repair, PARP inhibition leads to the accumulation of DNA double-strand breaks and synthetic lethality. Venadaparib's selectivity for PARP1 and PARP2 over PARP-5 contributes to its favorable safety profile. |
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| 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]
In vitro, venadaparib demonstrates potent inhibition of PARP1 (IC50 = 1.4 nM) and PARP2 (IC50 = 1.0 nM). The compound's activity is assessed using biochemical assays measuring PARP enzymatic activity. Venadaparib also shows activity in cell-based assays, where it inhibits PARP-mediated DNA repair and induces cell death in BRCA-deficient cancer cells. The compound's selectivity for PARP1 and PARP2 over other PARP family members contributes to its favorable safety profile. |
| 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]
In vivo, venadaparib has demonstrated antitumor activity in preclinical models. The compound is orally active and has been evaluated in xenograft models of BRCA-deficient cancers. Venadaparib's ability to inhibit PARP1 and PARP2 and induce synthetic lethality in cancer cells with DNA repair defects makes it a promising therapy for cancer patients. |
| Enzyme Assay |
Venadaparib's inhibition of PARP1 and PARP2 is assessed using biochemical enzyme assays. Recombinant PARP1 or PARP2 is incubated with the test compound, NAD+, and a DNA substrate; PARP activity is measured by detecting the incorporation of radiolabeled NAD+ or by using a colorimetric/fluorometric PARP assay. IC50 values are calculated from dose-response curves. Selectivity for PARP1 and PARP2 over other PARP family members is assessed by screening against a panel of PARP enzymes. These assays provide quantitative information on the potency and selectivity of venadaparib.
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| Cell Assay |
Venadaparib is tested on cultured cancer cells, particularly those with BRCA mutations or other DNA repair defects. Cells are treated with varying concentrations of venadaparib; PARP activity is assessed by measuring PAR polymer levels by Western blot or ELISA; DNA damage is assessed by measuring γH2AX levels; cell proliferation is assessed by MTT or CellTiter-Glo assays; apoptosis is assessed by Annexin V staining. These cell-based assays demonstrate the mechanism of action and antiproliferative activity of venadaparib.
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| Animal Protocol |
germline BRCA1-mutated ovarian cancer PDX model
o.g. Venadaparib has been evaluated in animal models of cancer. In these models, venadaparib is administered orally at various doses; tumor growth inhibition is assessed by measuring tumor volume; PARP activity and DNA damage are assessed in tumor tissue. These in vivo studies provide evidence for the efficacy of venadaparib. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies indicate that venadaparib is orally active. The compound's absorption, distribution, metabolism, and excretion have been characterized in preclinical studies. Venadaparib achieves therapeutic concentrations in plasma and tissues following oral administration. The compound's pharmacokinetic properties support once- or twice-daily oral dosing.
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| Toxicity/Toxicokinetics |
The toxicity profile of venadaparib is consistent with that of other PARP inhibitors. Common adverse effects associated with PARP inhibitors include fatigue, nausea, anemia, and thrombocytopenia. The safety profile of venadaparib is being evaluated in clinical trials.
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| References | |
| Additional Infomation |
Venadaparib is an orally bioavailable inhibitor of ribonucleotide polymerase (PARP) 1 and 2 with potential antitumor activity. After administration, Venadaparib selectively binds to PARP-1 and -2, blocking the PARP-1 and -2-mediated base excision repair pathway for single-stranded DNA (ssDNA) breaks. This promotes the conversion of ssDNA breaks into double-stranded DNA breaks, leading to genomic instability and ultimately inducing apoptosis. PARP catalyzes post-translational ADP-ribosylation modification of nucleoproteins, which signal and recruit other proteins to repair damaged DNA; ssDNA breaks activate PARP.
Venadaparib (IDX-1197, NOV140101) is a potent, selective, and orally active PARP inhibitor with IC50 values of 1.4 nM for PARP1 and 1.0 nM for PARP2. The compound prevents PARP-mediated repair of DNA single-strand breaks, leading to synthetic lethality in cancer cells with BRCA mutations or other defects in homologous recombination repair. Venadaparib is being developed for the treatment of solid tumors. The compound represents a promising therapy for cancer patients with DNA repair defects. |
| Molecular Formula |
C23H23FN4O2
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|---|---|
| Molecular Weight |
406.4527
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| Exact Mass |
406.18
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| Elemental Analysis |
C, 67.97; H, 5.70; F, 4.67; N, 13.78; O, 7.87
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| CAS # |
1681017-83-3
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| Related CAS # |
1681017-83-3; 1681020-60-9 (HCl)
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| PubChem CID |
117955898
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| Appearance |
White to yellow solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
703
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
YNBQAYKYNYRCCA-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
4-[[3-[3-[(cyclopropylamino)methyl]azetidine-1-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one
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| Synonyms |
Venadaparib; IDX1197; IDX 1197; IDX-1197
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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. View More
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. |
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04174716 | Active Recruiting |
Drug: IDX-1197 | Solid Tumors | Idience Co., Ltd. | November 6, 2019 | Phase 1 Phase 2 |
| NCT04725994 | Recruiting | Drug: IDX-1197+XELOX Drug: IDX-1197+Irinotecan |
Gastric Cancer | Idience Co., Ltd. | June 28, 2021 | Phase 1 |
| NCT05202912 | Completed | Drug: IDX-1197(After a meal) Drug: IDX-1197(fasting) |
Healthy Male | Idience Co., Ltd. | January 16, 2022 | Phase 1 |
| NCT03317743 | Completed | Drug: NOV140101 (IDX-1197) | Advanced Solid Tumors | Idience Co., Ltd. | August 29, 2017 | Phase 1 |
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