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| 5mg |
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| Other Sizes |
| Targets |
Olaparib-d8, like its non-deuterated parent, targets the nuclear enzyme poly(ADP-ribose) polymerase (PARP), specifically PARP1 and PARP2. PARP enzymes play a critical role in the DNA damage response, particularly in the repair of single-strand DNA breaks (SSBs) via the base excision repair (BER) pathway. By binding to the NAD+ binding site of PARP1 and PARP2, Olaparib inhibits PARP enzymatic activity and traps PARP on damaged DNA, leading to the accumulation of DNA double-strand breaks (DSBs). In cancer cells with homologous recombination repair (HRR) deficiency (e.g., those with BRCA1/2 mutations), these DSBs cannot be accurately repaired, resulting in synthetic lethality and cancer cell death. The deuterium labeling does not alter the mechanism of action.
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| ln Vitro |
No specific in vitro activity data is provided for Olaparib-d8 as it is an analytical standard. The parent compound Olaparib has been extensively characterized. Olaparib inhibits PARP1 with an IC50 of 5 nM and PARP2 with an IC50 of 1 nM in cell-free enzyme assays. In cell-based assays, Olaparib demonstrates potent cytotoxicity (EC50 in the low nanomolar range) against BRCA1/2-deficient cancer cell lines, including the BRCA2-deficient CAPAN-1 pancreatic cancer cell line (EC50 ∼50 nM) and the BRCA1-deficient MDA-MB-436 breast cancer cell line. The compound shows a high selectivity index, being significantly less toxic (30-500-fold) to BRCA-proficient cells. It induces the accumulation of gamma-H2AX and RAD51 foci, markers of DNA damage, and inhibits PARP activity in treated cells.
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| ln Vivo |
No specific in vivo data is provided for Olaparib-d8 as it is an analytical standard. The in vivo activity of the parent compound Olaparib is well-established. In xenograft mouse models of human BRCA-deficient cancers (e.g., CAPAN-1 pancreatic cancer, MDA-MB-436 breast cancer), oral administration of Olaparib (25-100 mg/kg) significantly inhibits tumor growth and induces tumor regression. Efficacy is dose-dependent and correlates with inhibition of PARP activity in tumor tissue (measured by loss of poly(ADP-ribose) (PAR) formation). In the CAPAN-1 xenograft model, Olaparib at 50 mg/kg twice daily for 28 days reduces tumor volume by >80% compared to vehicle controls. Olaparib has also demonstrated efficacy in patient-derived xenograft (PDX) models of ovarian, prostate, and small cell lung cancers with HRR deficiencies.
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| Enzyme Assay |
Olaparib-d8 is not used in cell-free assays for target engagement evaluation. For analytical method validation, the non-deuterated Olaparib is spiked into blank biological matrix (plasma, urine, tissue homogenate) to prepare calibration standards (typically range 0.5-1000 ng/mL). A fixed concentration of Olaparib-d8 (e.g., 50-100 ng/mL) is added as internal standard to each calibrator, quality control (QC) sample, and study sample. Proteins are precipitated with acetonitrile or methanol, and the supernatant is injected onto a C18 reversed-phase HPLC column coupled to a triple quadrupole mass spectrometer. Detection is performed in positive ion mode (ESI+) using multiple reaction monitoring (MRM): parent drug (e.g., m/z 434.2 → m/z 216.1) and internal standard (m/z 442.2 → m/z 220.1). The peak area ratio (analyte/IS) is plotted vs. nominal concentration. This method corrects for extraction recovery, matrix effects, and instrument variability.
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| Cell Assay |
For Olaparib-d8 analytical method validation, cellular samples are typically not used. For studies of cellular pharmacology, the non-deuterated Olaparib is used. A typical protocol for assessing PARP inhibition in cell culture uses BRCA-deficient cancer cells (e.g., CAPAN-1). Cells are seeded in 96-well plates (5×103 cells/well) and treated with Olaparib (0.01-100 microM) for 72-120 hours. Cell viability is measured using CellTiter-Glo. For PARP activity measurement, cells treated with Olaparib (0.1-10 microM) for 2-4 hours are lysed, and PAR levels are measured by ELISA. For DNA damage assessment, cells treated for 24 hours are fixed and stained with anti-gamma-H2AX antibody and analyzed by flow cytometry or immunofluorescence. Olaparib-d8 is used as an internal standard when measuring intracellular Olaparib concentrations by LC-MS/MS.
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| Animal Protocol |
In vivo pharmacokinetic studies to support efficacy studies use non-deuterated Olaparib. Female NOD/SCID mice bearing CAPAN-1 xenografts (200-300 mm3) are treated with Olaparib (25, 50, or 100 mg/kg) by oral gavage once daily for up to 28 days. For plasma PK studies, non-tumor-bearing mice (C57BL/6 or CD-1, n=3 per time point) receive a single oral dose (10-50 mg/kg). Blood is collected at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose. Plasma is separated and frozen. Olaparib concentrations are quantified by LC-MS/MS using Olaparib-d8 as internal standard. PK parameters (Cmax, Tmax, AUC, t½, oral bioavailability) are calculated using non-compartmental analysis. For tissue distribution studies, mice are euthanized at selected time points, and tissues (liver, kidney, brain, tumor) are collected and processed for LC-MS/MS analysis using the deuterated internal standard.
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| ADME/Pharmacokinetics |
Olaparib-d8 is a stable isotope-labeled compound. The molecular formula is C24H23D8FN4O3 (free base). The lyophilized powder should be stored at -20degC in a sealed container, protected from light and moisture, where it is stable for up to 3 years. For solution storage, stock solutions prepared in DMSO or acetonitrile should be stored at -80degC for up to 6 months. The compound is soluble in DMSO (10-20 mg/mL) and acetonitrile. For analytical use, working solutions are typically prepared by dilution in acetonitrile/water (50:50, v/v) or mobile phase. The internal standard is added to samples at a concentration of 5-100 ng/mL depending on the expected analyte concentration range. The compound should be handled using standard analytical chemistry practices.
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| Toxicity/Toxicokinetics |
This product is for research use only and is not for human therapeutic use. No specific toxicity data is available for the deuterated form. The parent compound Olaparib is an FDA-approved drug with an established safety profile. Common adverse effects in patients include fatigue, nausea, anemia, and thrombocytopenia. The deuterated internal standard is used at minute quantities (ng/mL levels in analytical solutions) that pose negligible risk. Standard laboratory safety practices (gloves, lab coat, safety glasses) should be followed. Avoid inhalation of powder. The compound is not intended for in vivo administration as a therapeutic. It is a research chemical for analytical method development.
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| References |
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| Additional Infomation |
Olaparib (brand name Lynparza) was the first PARP inhibitor approved by the FDA (in 2014) for the treatment of germline BRCA-mutated advanced ovarian cancer. It has since received approval for breast, pancreatic, and prostate cancers. Olaparib-d8 is a stable isotopic internal standard with eight deuterium atoms incorporated into the drug molecule, providing a mass shift of +8 Da relative to the parent compound (from m/z 434.2 to m/z 442.2). This internal standard is critical for accurate quantification of Olaparib in bioanalysis using LC-MS/MS, allowing correction for matrix effects, extraction efficiency, and instrument variability. The CAS number for non-deuterated Olaparib is 763113-22-0. This product is not a drug; it is a research chemical for use as an internal standard. Supplier information must not be included.
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| Molecular Formula |
C24H15D8FN4O3
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| Related CAS # |
Olaparib;763113-22-0;Olaparib-d5;2143107-56-4
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| Appearance |
Typically exists as solid at room temperature
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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) |
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
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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.
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