Description: BYK204165 is a novel, potent and selective poly(ADP-ribose) polymerase (PARP)-1 inhibitor with pIC50of 5.38 and 7.35 for PARP-2 and PARP-1 respectively.
| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
hPARP-1 ( pIC50 = 7.35 ); hPARP-1 ( pKi = 7.05 ); mPARP-2 ( pIC50 = 5.38 )
Poly(ADP-ribose) polymerase 1 (PARP-1), a nuclear enzyme involved in DNA repair, cell differentiation, proliferation, and tumor transformation. BYK204165 is a potent and selective PARP-1 inhibitor. It inhibits cell-free recombinant human PARP-1 (hPARP-1) with a pIC50 of 7.35 (pKi=7.05) and murine PARP-2 (mPARP-2) with a pIC50 of 5.38. The compound displays approximately 100-fold selectivity for PARP-1 over PARP-2. |
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| ln Vitro |
BYK204165 showed strong inhibitory suppression of enzyme activity in human PARP-1 kinetic tests, yielding a pKi value of 7.05 [1]. In C4I cells, BYK204165 has a negligible inhibitory effect on PARP (pIC50 = 5.75) [1].
BYK204165 potently inhibits PARP-1 enzymatic activity with a pIC50 of 7.35 (equivalent to an IC50 of approximately 45 nM) and a pKi of 7.05 for human PARP-1. It shows significantly weaker activity against murine PARP-2 with a pIC50 of 5.38 (approximately 4.2 μM). The compound displays approximately 100-fold selectivity for PARP-1 over PARP-2. BYK204165 is cell-permeable and can effectively inhibit PARP-1 activity in cellular contexts. |
| ln Vivo |
Due to its half-life (t1/2) of 23 minutes when measured outside of the droplet, BYK204165 has not been investigated in vivo [1].
In vivo activity data for BYK204165 is limited as the compound is primarily used as a research tool for in vitro studies. The compound's potent and selective PARP-1 inhibition makes it a valuable tool for studying the role of PARP-1 in various biological processes including DNA repair, cell differentiation, proliferation, and tumor transformation. Further in vivo studies are needed to fully characterize its therapeutic potential. |
| Enzyme Assay |
In vitro enzyme assays for BYK204165 involve measuring the inhibition of PARP-1 enzymatic activity using cell-free recombinant human PARP-1 (hPARP-1). The enzyme is incubated with a PARP substrate (such as biotinylated NAD+) and various concentrations of BYK204165. PARP activity is measured by detecting the incorporation of ADP-ribose into acceptor proteins. pIC50 and pKi values are determined from concentration-response curves.
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| Cell Assay |
In vitro cellular assays for BYK204165 involve treating cell lines with the compound and measuring PARP-1 inhibition through assessment of poly(ADP-ribose) (PAR) accumulation or DNA damage repair capacity. Cells are treated with various concentrations of BYK204165, followed by DNA damage induction (e.g., via hydrogen peroxide or alkylating agents). PAR levels are measured by immunofluorescence or ELISA. The compound's ability to sensitize cells to DNA-damaging agents is assessed by cell viability assays.
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| Animal Protocol |
In vivo animal studies for BYK204165 are limited as the compound is primarily used as a research tool for in vitro applications. The compound's potent and selective PARP-1 inhibition could be studied in xenograft models of cancer, where BYK204165 would be administered alone or in combination with DNA-damaging agents. Further studies are needed to fully characterize its in vivo efficacy and pharmacokinetic properties.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for BYK204165 is limited and primarily derived from research use. The compound is soluble in DMSO at 50 mg/mL (198.2 mM) but is insoluble in water and ethanol. For in vivo administration, BYK204165 can be formulated as a homogeneous suspension in CMC-Na at concentrations up to 5 mg/mL for oral administration. Further pharmacokinetic studies are needed to support its development as a therapeutic agent.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of BYK204165 are limited. As a PARP-1 inhibitor, the compound has potential applications in cancer research, particularly in the context of synthetic lethality with BRCA mutations. Comprehensive toxicological evaluation is needed before clinical development. The compound's selectivity for PARP-1 over PARP-2 (approximately 100-fold) may contribute to a more favorable toxicity profile compared to less selective PARP inhibitors.
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| References | |
| Additional Infomation |
BYK204165 is a potent and selective PARP-1 inhibitor widely used in cancer research to study DNA repair mechanisms, synthetic lethality, and the role of PARP-1 in cell differentiation, proliferation, and tumor transformation. The compound inhibits human PARP-1 with a pIC50 of 7.35 (pKi=7.05) and murine PARP-2 with a pIC50 of 5.38, displaying approximately 100-fold selectivity for PARP-1. BYK204165 is a cell-permeable isoquinolinedione compound.
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| Molecular Formula |
C15H12N2O2
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| Molecular Weight |
252.26798
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| Exact Mass |
252.09
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| Elemental Analysis |
C, 71.42; H, 4.79; N, 11.10; O, 12.68
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| CAS # |
1104546-89-5
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| PubChem CID |
25113764
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| Appearance |
Brown to reddish brown solid powder
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| LogP |
1.846
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
19
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| Complexity |
430
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1C=CC=C1/C=C1\C2C(=CC=CC=2)C(=O)NC\1=O
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| InChi Key |
BTYSIDSTHDDAJW-LCYFTJDESA-N
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| InChi Code |
InChI=1S/C15H12N2O2/c1-17-8-4-5-10(17)9-13-11-6-2-3-7-12(11)14(18)16-15(13)19/h2-9H,1H3,(H,16,18,19)/b13-9-
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| Chemical Name |
(4Z)-4-[(1-methylpyrrol-2-yl)methylidene]isoquinoline-1,3-dione
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| Synonyms |
BYK204165; BYK 204165; BYK-204165; RT017290; RT-017290; RT 017290
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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) |
DMSO : 50~125 mg/mL (198.2~495.5 mM)
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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 | 3.9640 mL | 19.8200 mL | 39.6401 mL | |
| 5 mM | 0.7928 mL | 3.9640 mL | 7.9280 mL | |
| 10 mM | 0.3964 mL | 1.9820 mL | 3.9640 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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