Pamiparib maleate, the maleate salt of pamiparib (formerly BGB-290), is a selective inhibitor of PARP1 and PARP2 with IC50 values of 0.83 and 0.11 nM, respectively. Pamiparib is being studied in clinical settings and may be used to treat a number of cancers, including solid tumors. In China, it was accepted in 2021.
Physicochemical Properties
| Molecular Formula | C16H15FN4O | |
| Molecular Weight | 414.39 | |
| Exact Mass | 298.12 | |
| Elemental Analysis | C, 64.42; H, 5.07; F, 6.37; N, 18.78; O, 5.36 | |
| CAS # | 2086689-94-1 | |
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| Appearance | Solid powder | |
| InChi Key | CQDVXYMHPXRRCS-YIIKDHGFSA-N | |
| InChi Code | InChI=1S/2C16H15FN4O.3C4H4O4/c2*1-16-3-2-4-21(16)7-11-13-12-9(15(22)20-19-11)5-8(17)6-10(12)18-14(13)16;3*5-3(6)1-2-4(7)8/h2*5-6,18H,2-4,7H2,1H3,(H,20,22);3*1-2H,(H,5,6)(H,7,8)/b;;3*2-1-/t2*16-;;;/m11.../s1 | |
| Chemical Name | (Z)-but-2-enedioic acid;(2R)-14-fluoro-2-methyl-6,9,10,19-tetrazapentacyclo[14.2.1.02,6.08,18.012,17]nonadeca-1(18),8,12(17),13,15-pentaen-11-one | |
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| 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 |
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| 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
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| Enzyme Assay | BGB-290 exhibited strong potency for PARP1/2 (IC50 = 0.83 and 0.11 nM, respectively) and high selectivity over other PARP in the biochemical assays. BGB-290 exhibited strong potency for PARP1/2 (IC50 = 0.83 and 0.11 nM, respectively) and excellent selectivity against other PARP enzymes in the biochemical assays. Using a fluorescence polarization (FP) binding assay, the DNA-trapping activity of BGB-290 was determined. With an IC50 of 13 nM, BGB-290 demonstrated strong DNA-trapping activity. With an IC50 of 0.24 nM, BGB-290 suppressed intracellular PAR formation in the cellular experiments. BGB-290 showed significant sensitivity to tumor cell lines with homologous recombination defects. When BGB-290 was administered orally, it was observed that the MDA-MB-436 (BRCA1 mutant) breast cancer xenograft showed time- and dose-dependent inhibition of PARylation, which correlated well with the concentrations of tumor drug. BGB-290 produced PAR inhibition that was more persistent than olaparib. BGB-290 showed remarkable anti-tumor activity in this model, more than ten times more potent than olaparib, which is consistent with this finding. | |
| Cell Assay | Three of the seven SCLC cell lines examined in the panel were BGB-290 sensitive. Using patient biopsy samples from Beijing Cancer Hospital, in-house primary tumor models for SCLC were created. Using eight SCLC primary tumor models, the anti-tumor properties of BGB-290 alone or in combination with etoposide/carboplatin (E/C) were assessed. In these models, BGB-290 displayed only marginal single agent activity. The clinical response seen in these patients was consistent with the sensitivity of six out of the eight models (75%) to E/C treatment.In these chemosensitive models, the addition of BGB-290 as maintenance therapy or concurrent treatment greatly extended the duration of the response. The combined effects of BGB-290 and E/C were less successful in the two chemo-insensitive models. Throughout the trial, adding BGB-290 to the chemotherapy regimen was well tolerated. | |
| Animal Protocol | 8 SCLC primary tumor models. | |
| References |
[1]. BGB-290, a novel PARP inhibitor with unique brain penetration ability, demonstrated strong synergism with temozolomide in subcutaneous and intracranial xenograft models. Cancer Res (2015) 75 (15_Supplement): 1651. |
Solubility Data
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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 (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 | 2.4132 mL | 12.0659 mL | 24.1319 mL | |
| 5 mM | 0.4826 mL | 2.4132 mL | 4.8264 mL | |
| 10 mM | 0.2413 mL | 1.2066 mL | 2.4132 mL |