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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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Purity: ≥98%
Pamiparib (also known as BGB-290; trade name in China: Baihuize) is a novel, potent and selective inhibitor of PARP1/2 approved in China for cancer treatment. It uses a mechanism known as "synthetic lethality" to destroy tumor cells. Compared to other PARP enzymes, dapagliparib exhibits a high degree of selectivity. Its DMPK (drug metabolism and pharmacokinetic) profiles are favorable. Using 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 counteract tumor cells' resistance to chemotherapy and radiation, as well as increase the cytotoxicity of agents that damage DNA.
| Targets |
PARP2 ( IC50 = 0.11 nM ); PARP1 ( IC50 = 0.83 nM )
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
BGB-290 showed excellent selectivity over other PARP enzymes and significant potency for PARP1/2 (IC50 = 0.83 and 0.11 nM, respectively) in the biochemical tests. The assay used to measure BGB-290's DNA-trapping activity was the fluorescence polarization (FP) binding method. BGB-290 exhibited a strong ability to trap DNA, with an IC50 of 13 nM. BGB-290 inhibited intracellular PAR formation in the cellular assays, with an IC50 of 0.24 nM. BGB-290 had a strong effect on tumor cell lines with homologous recombination defects. In an MDA-MB-436 (BRCA1 mutant) breast cancer xenograft, oral administration of BGB-290 led to time- and dose-dependent inhibition of PARylation, which correlated well with the tumor drug concentrations. 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.
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| Cell Assay |
Three of the seven SCLC cell lines that were tested showed sensitivity to BGB-290. Using patient biopsy samples from Beijing Cancer Hospital, internal SCLC primary tumor models were created. Eight primary tumor models of SCLC were used to assess the anti-tumor activities of BGB-290, either alone or in conjunction with etoposide/carboplatin (E/C). In these models, BGB-290 exhibited only marginal single agent activity. In line with the clinical response seen in these patients, six of the eight models (or75%) showed sensitivity to E/C treatment. In these chemo-sensitive models, the addition of BGB-290 as maintenance therapy or concurrent treatment greatly extended the duration of the response. BGB-290 and E/C combo had less of an impact in the two chemo-insensitive models. Throughout the trial, BGB-290 was well tolerated as an addition to the chemotherapy regimen.
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| Animal Protocol |
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| Additional Infomation |
Pamiparib is under investigation in clinical trial NCT03933761 (Pamiparib in Fusion Positive, Reversion Negative High Grade Serous Ovarian Cancer or Carcinosarcoma With BRCA1/2 Gene Mutations If Progression on Substrate Poly ADP Ribose Polymerase Inhibitbor (PARPI) or Chemotherapy).
Pamiparib is an orally bioavailable inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP), with potential antineoplastic activity. Upon administration, pamiparib selectively binds to PARP and prevents PARP-mediated repair of single-strand DNA breaks via the base-excision repair (BER) pathway. This enhances the accumulation of DNA strand breaks, promotes genomic instability, and eventually leads to apoptosis. PARP is activated by single-strand DNA breaks and, subsequently, catalyzes post-translational ADP-ribosylation of nuclear proteins which then transduce signals to recruit other proteins to repair damaged DNA. Pamiparib may both potentiate the cytotoxicity of DNA-damaging agents and reverse tumor cell chemo- and radioresistance. Drug Indication Treatment of gastric and gastroesophageal junction adenocarcinoma |
| Molecular Formula |
C16H15FN4O
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| Molecular Weight |
298.31
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| Exact Mass |
298.122
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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 # |
1446261-44-4
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| Related CAS # |
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| PubChem CID |
135565554
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.7±0.1 g/cm3
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| Index of Refraction |
1.829
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| LogP |
0.02
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
22
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| Complexity |
566
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC1=CC2C(NN=C3C4C=2C(=C1)NC=4[C@@]1(C)CCCN1C3)=O
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| InChi Key |
DENYZIUJOTUUNY-MRXNPFEDSA-N
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| InChi Code |
InChI=1S/C16H15FN4O/c1-16-3-2-4-21(16)7-11-13-12-9(15(22)20-19-11)5-8(17)6-10(12)18-14(13)16/h5-6,18H,2-4,7H2,1H3,(H,20,22)/t16-/m1/s1
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| Chemical Name |
(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) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (7.54 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 22.5 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. Solubility in Formulation 2: 5%DMSO+ 40%PEG300+ 5%Tween 80+ 50%ddH2O: 3.0mg/ml (10.06mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3522 mL | 16.7611 mL | 33.5222 mL | |
| 5 mM | 0.6704 mL | 3.3522 mL | 6.7044 mL | |
| 10 mM | 0.3352 mL | 1.6761 mL | 3.3522 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 |
| NCT05376722 | Recruiting | Drug: pamiparib Drug: abiraterone |
Neoadjuvant Therapy | Hongqian Guo | February 22, 2022 | Phase 2 |
| NCT05494580 | Recruiting | Drug: Pamiparib Drug: Surufatinib |
Ovarian Cancer Ovarian Carcinoma |
Sun Yat-sen University | September 22, 2022 | Phase 1 Phase 2 |
| NCT04614909 | Recruiting | Drug: Pamiparib Drug: Olaparib |
Glioblastoma Glioblastoma Multiforme |
Nader Sanai | January 11, 2021 | Early Phase 1 |
| NCT04985721 | Recruiting | Drug: Pamiparib Drug: Tislelizumab |
Cancer | Peter MacCallum Cancer Centre, Australia |
February 24, 2022 | Phase 2 |
| NCT05044871 | Not yet recruiting | Drug: Pamiparib Drug: Bevacizumab |
Ovarian Cancer | Tongji Hospital | January 1, 2023 | Phase 2 |
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