Rucaparib acetate (AG-014699) is a novel and orally bioactive inhibitor of PARP proteins (PARP-1, PARP-2 and PARP-3) with anticancer activity. It inhibits PARP1 with a Ki of 1.4 nM. Rucaparib is also a modest hexose-6-phosphate dehydrogenase (H6PD) inhibitor.
Physicochemical Properties
| Molecular Formula | C21H22FN3O3 |
| Molecular Weight | 383.416088581085 |
| Exact Mass | 383.165 |
| CAS # | 773059-23-7 |
| Related CAS # | Rucaparib;283173-50-2 |
| PubChem CID | 69552812 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 3.789 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 28 |
| Complexity | 497 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C(=O)(O)C.O=C1NCCC2=C(C3C=CC(CNC)=CC=3)NC3=CC(F)=CC1=C23 |
| InChi Key | NMSYMXVEBNHEFJ-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C19H18FN3O.C2H4O2/c1-21-10-11-2-4-12(5-3-11)18-14-6-7-22-19(24)15-8-13(20)9-16(23-18)17(14)15;1-2(3)4/h2-5,8-9,21,23H,6-7,10H2,1H3,(H,22,24);1H3,(H,3,4) |
| Chemical Name | acetic acid;6-fluoro-2-[4-(methylaminomethyl)phenyl]-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-9-one |
| 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
| ln Vitro | Rucaparib (AG014699) acetate is a potential N-demethylation metabolite of AG14644[1]. Rucaparib acetate (0.1, 1, 10, 100 μM; 24 hours) is cytotoxic, with an LC50 of 5 μM in Capan-1 (BRCA2 mutant) cells and only 100 nM in MX-1 (BRCA1 mutant) cells [2]. Rucaparib acetate causes radio-sensitization by inhibiting NF-κB activity downstream, without affecting SSB repair. Rucaparib acetate targets NF-κB triggered by DNA damage, overcoming the toxicity of traditional NF-κB inhibitors while maintaining essential inflammatory functions [5]. Rucaparib acetate inhibits PARP-1 activity by 97.1% at 1 μM in permeabilized D283Med cells [6]. |
| ln Vivo | AG14584 and rutapib (AG014699) acetate both markedly increase the toxicity of temozolomide. Temozolomide-induced body weight loss is greatly increased by rucaparib (1 mg/kg) acetate. There is a 50% increase in the temozolomide-induced tumor growth delay when rucaparib (0.1 mg/kg) acetate is administered[1]. The tumor's growth is considerably inhibited by rucaparib (10 mg/kg for ip or 50, 150 mg/kg for po; daily for 5 days per week for 6 weeks) acetate. One complete tumor regression and two persistent partial regressions are observed[2]. With three full regressions, rucaparib (150 mg/kg; po; once weekly for six weeks or three times weekly for six weeks) acetate exhibits the strongest anticancer effect[2]. In NB1691 and SHSY5Y xenografts, rucaparib acetate improves the anticancer efficacy of temozolomide and shows full and long-lasting tumor regression[6]. |
| References |
[1]. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol Cancer Ther, 2007, 6(3), 945-956. [2]. Tumour cell retention of rucaparib, sustained PARP inhibition and efficacy of weekly as well as daily schedules. Br J Cancer. 2014 Apr 15;110(8):1977-84. [3]. Rucaparib: A Review in Ovarian Cancer. Target Oncol. 2019 Apr;14(2):237-246. [4]. Hexose-6-phosphate dehydrogenase blockade reverses prostate cancer drug resistance in xenograft models by glucocorticoid inactivation. Sci Transl Med. 2021 May 26;13(595):eabe8226. [5]. NF-κB mediates radio-sensitization by the PARP-1 inhibitor, AG-014699. Oncogene, 2012, 31(2), 251-264. [6]. Inhibition of poly(ADP-ribose) polymerase-1 enhances temozolomide and topotecan activity against childhood neuroblastoma. Clin Cancer Res, 2009, 15(4), 1241-1249. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6081 mL | 13.0405 mL | 26.0811 mL | |
| 5 mM | 0.5216 mL | 2.6081 mL | 5.2162 mL | |
| 10 mM | 0.2608 mL | 1.3041 mL | 2.6081 mL |