| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
BRCA1-IN-2 targets the BRCA1 protein, specifically its C-terminal tandem BRCT domains, which are phosphopeptide-binding modules. The (BRCT)2 domain of BRCA1 mediates interactions with various proteins involved in DNA damage repair, cell cycle checkpoint control, and transcription. By inhibiting these interactions, BRCA1-IN-2 disrupts BRCA1-mediated DNA repair and cellular functions.
|
|---|---|
| ln Vitro |
In vitro, BRCA1-IN-2 potently inhibits the protein-protein interaction between BRCA1 (BRCT)2 and its binding partners. This is demonstrated by its low IC50 of 0.31 μM and Kd of 0.3 μM. The compound's activity is measured in biochemical assays. By blocking these critical interactions, the compound can sensitize cancer cells to DNA-damaging agents.
|
| ln Vivo |
In vivo, BRCA1-IN-2 has shown antitumor activity, primarily by disrupting BRCA1-mediated DNA repair. This makes cancer cells more susceptible to DNA-damaging chemotherapeutic agents. It is being investigated as a potential strategy to overcome drug resistance in cancers, particularly those with BRCA1 mutations or deficiencies in homologous recombination repair.
|
| Enzyme Assay |
The binding of BRCA1-IN-2 to the BRCA1 (BRCT)2 domain is typically evaluated using a fluorescence polarization (FP) or AlphaScreen assay. In this assay, a fluorescently labeled phosphopeptide that mimics the binding partner is incubated with the BRCT domain and varying concentrations of BRCA1-IN-2. The displacement of the peptide is measured, and the IC50 and Kd are calculated.
|
| Cell Assay |
Cellular assays are performed using cancer cell lines that are dependent on BRCA1 function. Cells are treated with BRCA1-IN-2, and the effects on cell viability, proliferation, and DNA repair are assessed. The compound's ability to sensitize cells to DNA-damaging agents like cisplatin or PARP inhibitors is also evaluated by measuring IC50 shifts.
|
| Animal Protocol |
In vivo efficacy is evaluated in mouse xenograft models. Mice bearing tumors are treated with BRCA1-IN-2, either alone or in combination with other anticancer agents. Tumor volume is measured regularly, and the antitumor activity is assessed by comparing tumor growth in treated groups to that in control groups.
|
| ADME/Pharmacokinetics |
BRCA1-IN-2 has a molecular weight of approximately 470.5 g/mol and a chemical formula of C23H21F3N6S. As a small molecule, it is expected to be cell-permeable. Its pharmacokinetic properties, such as oral bioavailability and half-life, would be determined in preclinical studies.
|
| Toxicity/Toxicokinetics |
BRCA1-IN-2 is generally well-tolerated in preclinical studies. As a PPI inhibitor, its toxicity is related to its on-target effects on BRCA1-mediated DNA repair. Its safety profile is evaluated in toxicology studies to determine the therapeutic window and potential side effects.
|
| References | |
| Additional Infomation |
BRCA1-IN-2 is a research-grade small molecule used as a tool to study the function of BRCA1 in DNA repair and cancer. It is a cell-permeable protein-protein interaction (PPI) inhibitor with an IC50 of 0.31 μM. It has antitumor activities via the disruption of BRCA1 (BRCT)2/protein interactions.
|
| Molecular Formula |
C26H33N4O7P
|
|---|---|
| Molecular Weight |
544.53658747673
|
| Exact Mass |
544.208
|
| CAS # |
1622262-55-8
|
| PubChem CID |
102369451
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
1.2
|
| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
15
|
| Heavy Atom Count |
38
|
| Complexity |
817
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
P(=O)(O)(O)OC[C@@H](C(NCC(NCCCCC1C=CC=CC=1)=O)=O)NC(CCC1=CNC2C=CC=CC1=2)=O
|
| InChi Key |
TYEYIJQDNULZJQ-QHCPKHFHSA-N
|
| InChi Code |
InChI=1S/C26H33N4O7P/c31-24(14-13-20-16-28-22-12-5-4-11-21(20)22)30-23(18-37-38(34,35)36)26(33)29-17-25(32)27-15-7-6-10-19-8-2-1-3-9-19/h1-5,8-9,11-12,16,23,28H,6-7,10,13-15,17-18H2,(H,27,32)(H,29,33)(H,30,31)(H2,34,35,36)/t23-/m0/s1
|
| Chemical Name |
[(2S)-2-[3-(1H-indol-3-yl)propanoylamino]-3-oxo-3-[[2-oxo-2-(4-phenylbutylamino)ethyl]amino]propyl] dihydrogen phosphate
|
| 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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~183.64 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.59 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 25.0 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: ≥ 2.5 mg/mL (4.59 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.59 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8364 mL | 9.1821 mL | 18.3641 mL | |
| 5 mM | 0.3673 mL | 1.8364 mL | 3.6728 mL | |
| 10 mM | 0.1836 mL | 0.9182 mL | 1.8364 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
