| Size | Price | Stock | Qty |
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| 25mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Pamiparib targets PARP1 and PARP2 (poly ADP-ribose polymerase 1 and 2), enzymes involved in DNA repair through the base-excision repair pathway. By selectively inhibiting PARP1/2, it induces synthetic lethality in tumor cells with BRCA1/2 mutations or homologous recombination repair deficiencies, leading to the accumulation of DNA damage and cell death.
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| ln Vitro |
Pamiparib (also known as BGB-290) is a novel, potent and selective inhibitor of PARP1 and PARP2, with IC50 values in enzymatic tests of 0.83 and 0.11 nM, respectively. Compared to other PARP enzymes, dapagliparib exhibits high selectivity. Its drug metabolism and pharmacokinetic (DMPK) profiles are favorable. Through the base-excision repair (BER) pathway, pampiparib binds to PARP specifically and inhibits PARP from repairing single-strand DNA breaks. This process increases the accumulation of DNA strand breaks, causes genomic instability, and ultimately results in apoptosis. Pamiparib has the ability to reverse tumor cells' resistance to chemotherapy and radiation, as well as increase the cytotoxicity of agents that damage DNA. Currently undergoing clinical trials, pemaparib shows promise as a treatment for a number of cancers, including solid tumors.
In vitro, Pamiparib selectively inhibits PARP1 and PARP2 with IC50 values of 0.83 nM and 0.11 nM, respectively. It has the ability to reverse tumor cells' resistance to chemotherapy and radiation, as well as increase the cytotoxicity of DNA-damaging agents. It can effectively penetrate the blood-brain barrier. |
| ln Vivo |
BGB-290 or Etoposide/carboplatin (E/C) alone were tested for their antitumor effects in eight SCLC primary tumor models. In these models, BGB-290 displayed little activity from a single agent. In accordance with the clinical response seen in these patients, six of the eight models (or75%) showed sensitivity to E/C therapy. These chemosensitive models' response duration was markedly extended by the addition of BGB-290 as maintenance therapy or concurrent treatment. BGB-290 plus E/C combo was less successful in the two chemo-insensitive models. BGB-290 was well tolerated when added to the chemotherapy regimen during the whole investigation.
In vivo, Pamiparib maleate has shown antitumor activity in preclinical models. It has been investigated in clinical studies for the treatment of various cancers including solid tumors. It was approved in China in 2021. However, it has also been reported to cause cerebral hemorrhage, brain atrophy, and movement disorders in zebrafish embryos. |
| 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.
PARP1/2 inhibitory activity is determined using cell-free enzyme assays with recombinant PARP1 and PARP2 enzymes. Incorporation of radiolabeled NAD⁺ into poly(ADP-ribose) polymers is measured, and IC50 values are calculated from dose-response curves. |
| 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.
Cellular assays for Pamiparib use cancer cell lines with homologous recombination repair deficiencies, such as BRCA-mutant cells. Cells are treated with varying concentrations of Pamiparib, and DNA damage (γH2AX foci) and cell viability are assessed. PARP trapping and synthetic lethality are evaluated. |
| Animal Protocol |
8 SCLC primary tumor models.
In vivo animal studies for Pamiparib are conducted in mouse xenograft models of BRCA-mutant or homologous recombination-deficient tumors. The compound is administered orally due to its oral bioavailability. Tumor growth inhibition, DNA damage markers, and survival are assessed. |
| ADME/Pharmacokinetics |
Pamiparib maleate has the molecular formula C₄₄H₄₂F₂N₈O₁₄ with a molecular weight of 944.859. It has favorable drug metabolism and pharmacokinetic properties. It can effectively penetrate the blood-brain barrier. It is orally bioavailable.
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| Toxicity/Toxicokinetics |
No specific toxicity data are detailed in the available references. However, Pamiparib has been reported to cause cerebral hemorrhage, brain atrophy, and movement disorders in zebrafish embryos, indicating potential neurotoxicity. Clinical safety data would be available from its clinical development and approval.
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| References | |
| Additional Infomation |
Pamiparib maleate (BGB-290 maleate) is an approved PARP inhibitor. It was approved in China in 2021 for the treatment of various cancers including solid tumors. It is a highly potent and selective PARP inhibitor with favorable pharmacokinetic properties. Its ability to penetrate the blood-brain barrier may offer advantages for treating brain metastases.
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| Molecular Formula |
C16H15FN4O
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| Molecular Weight |
414.39
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| Exact Mass |
298.12
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| Elemental Analysis |
C, 64.42; H, 5.07; F, 6.37; N, 18.78; O, 5.36
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| CAS # |
2086689-94-1
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| Related CAS # |
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| PubChem CID |
168012555
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
10
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| Hydrogen Bond Acceptor Count |
20
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
68
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| Complexity |
685
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@]12N(CC3=NNC(=O)C4=C5C3=C1NC5=CC(=C4)F)CCC2.C[C@]12N(CC3=NNC(=O)C4=C5C3=C1NC5=CC(=C4)F)CCC2.C(=C\\C(=O)O)\\C(=O)O.C(=C\\C(=O)O)\\C(=O)O.C(=C\\C(=O)O)\\C(=O)O
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| InChi Key |
CQDVXYMHPXRRCS-YIIKDHGFSA-N
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| 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
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| 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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| Synonyms |
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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 |
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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)
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| Solubility (In Vitro) |
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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.) |
| 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 |
*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.
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