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| Targets |
The primary target of BLM-IN-1 is the Bloom syndrome protein (BLM), a member of the RecQ family of DNA helicases that plays a critical role in maintaining genomic stability. BLM is involved in DNA repair, recombination, and replication, and its dysfunction is associated with Bloom syndrome, a rare genetic disorder characterized by genomic instability and cancer predisposition. BLM-IN-1 inhibits BLM with an IC₅0 of 0.95 microM and binds with a Kd of 1.81 microM. By inhibiting BLM helicase activity, the compound disrupts DNA repair processes, leading to DNA damage accumulation, apoptosis, and proliferation arrest in cancer cells.
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| ln Vitro |
BLM-IN-1 (compound 29) has a KD of 1.81 μM and a good capacity to bind BLM [1]. At an IC50 of 0.95 μM, BLM-IN-1 can inhibit BLM[1]. BLM-IN-1 (1.0 μM) not only prevents BLM from unwinding, but it also messes with BLM's ability to attach to DNA [1]. BLM-IN-1 (0-1.0 μM) inhibits the recruitment of BLM to DSB sites, which controls homologous recombination [1]. Apoptosis and a DNA damage response are induced by BLM-IN-1 (1.0, 2.0 μM; 48 hours) [1]. In 48 hours, BLM-IN-1 (0.1, 1.0, and 2.0 μM) causes synthetic interactions and proliferation arrest [1].
In vitro studies have demonstrated that BLM-IN-1 is a potent inhibitor of BLM with an IC₅0 of 0.95 microM and a Kd of 1.81 microM. The compound induces DNA damage response, apoptosis, and proliferation arrest in cancer cells. BLM-IN-1 has been shown to be effective in various cancer cell lines, making it a promising candidate for anticancer therapy. The compound's mechanism of action involves inhibition of BLM helicase activity, leading to the accumulation of DNA damage and subsequent cell death. BLM-IN-1 is used as a research tool to study the role of BLM in DNA repair and genomic stability and to validate BLM as a therapeutic target. |
| ln Vivo |
In vivo studies of BLM-IN-1 are likely focused on evaluating its antitumor efficacy in animal models of cancer. As a BLM inhibitor that induces DNA damage and apoptosis in cancer cells, the compound has the potential to inhibit tumor growth in vivo. BLM-IN-1 may be effective against cancers that are dependent on BLM for DNA repair and survival. Further studies are needed to evaluate its pharmacokinetic properties, bioavailability, and efficacy in various animal models. The compound's ability to induce DNA damage and apoptosis suggests it could be a valuable addition to the arsenal of anticancer therapies, particularly for tumors with defects in other DNA repair pathways.
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| Enzyme Assay |
For in vitro enzyme/receptor binding assays, BLM-IN-1 is evaluated using helicase activity assays that measure the unwinding of DNA by BLM. The compound is incubated with recombinant BLM protein, a DNA substrate (typically a forked or duplex DNA with a fluorescent or radioactive label), and ATP at various concentrations. BLM-mediated DNA unwinding is quantified by gel electrophoresis, fluorescence polarization, or other detection methods. IC₅0 values are determined from dose-response curves. Binding affinity (Kd) is measured using surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), or other biophysical methods. Selectivity profiling against other helicases may be performed to confirm specificity.
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| Cell Assay |
Western Blot analysis [1]
Cell Types: HCT116 cells Tested Concentrations: 0.5, 1.0 μM Incubation Duration: 24 h Experimental Results: The levels of pATM and p-ATR were Dramatically increased in the injury response. Immunofluorescence[1] Cell Types: HCT116 Cell Tested Concentrations: 1.0 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced RAD51 accumulation at DSB sites. Cell proliferation experiment [1] Cell Types: HCT116 Cell Tested Concentrations: 0.1, 1.0, 2.0 μM Incubation Duration: 48 h Experimental Results: HCT116 cells demonstrated significant inhibition of proliferation in a dose-dependent manner. Apoptosis analysis [1] Cell Types: HCT116 Cell Tested Concentrations: 1.0, 2.0 μM Incubation Duration: 48 h Experimental Results: The proportion of apoptotic cells increased in a concentration-dependent manner, and the expression levels of cleaved caspase-3 and cleaved caspase-7 were up-regulated, and Cutting PARP. For in vitro cellular experiments, BLM-IN-1 is tested in cancer cell lines to evaluate its effects on cell viability, proliferation, and DNA damage. Cells are cultured in appropriate media and treated with various concentrations of the compound (typically ranging from nanomolar to micromolar). Cell viability and proliferation are assessed using MTT, CellTiter-Glo, or colony formation assays. DNA damage is evaluated using gamma-H2AX staining, comet assays, or other DNA damage markers. Apoptosis is assessed using Annexin V staining, caspase activity assays, or TUNEL staining. Cell cycle analysis is performed by flow cytometry. The compound's effects on BLM protein levels and activity can be confirmed by Western blotting. |
| Animal Protocol |
For in vivo animal experiments, BLM-IN-1 can be administered to tumor-bearing mice via various routes including oral gavage, intravenous injection, or intraperitoneal injection, depending on its solubility and pharmacokinetic properties. Xenograft models using human cancer cell lines in immunodeficient mice are commonly used to evaluate antitumor efficacy. Typical dosing regimens may range from 1 to 50 mg/kg administered daily or intermittently. Tumor volume is measured regularly, and tumor growth inhibition is calculated. DNA damage and apoptosis markers in tumors are assessed by immunohistochemistry or Western blotting. Body weight and overall health are monitored. Pharmacokinetic parameters are measured to correlate drug exposure with efficacy.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of BLM-IN-1 are not extensively detailed in the public literature. As a small molecule with a molecular weight of 462.60 g/mol, it may have reasonable oral bioavailability and tissue distribution. The presence of fluorine and the lipophilic nature of the compound may influence its metabolic stability and clearance. Detailed parameters such as Cₘₐₓ, Tₘₐₓ, AUC, half-life, and clearance would need to be determined through comprehensive PK studies in relevant animal models. The compound's protein binding, metabolism, and excretion pathways remain to be fully characterized. Formulation development may be necessary for optimal in vivo administration.
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| Toxicity/Toxicokinetics |
Toxicological data for BLM-IN-1 are limited, as the compound is primarily a research tool. Preliminary studies suggest that BLM-IN-1 induces DNA damage and apoptosis in cancer cells, which could also affect normal rapidly dividing cells. Comprehensive toxicology studies including acute and repeated-dose toxicity, genotoxicity, and cardiotoxicity assessments would be needed for further development. As a DNA helicase inhibitor, potential on-target effects related to BLM's role in normal DNA repair should be considered. Appropriate safety precautions should be taken when handling this compound, including the use of personal protective equipment and adherence to institutional safety guidelines.
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| References | |
| Additional Infomation |
BLM-IN-1 is a research compound used to study BLM biology and develop anticancer therapies targeting BLM. No clinical trials or regulatory approvals have been reported for this compound as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound is a potent BLM inhibitor with an IC₅0 of 0.95 microM and a Kd of 1.81 microM. BLM-IN-1 induces DNA damage response, apoptosis, and proliferation arrest in cancer cells, making it a promising candidate for further development as an anticancer therapy.
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| Molecular Formula |
C28H35FN4O
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|---|---|
| Molecular Weight |
462.602110147476
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| Exact Mass |
462.279
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| CAS # |
2056014-40-3
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| PubChem CID |
137649032
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
34
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| Complexity |
754
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1=CC2=C(C=C1NCCCN(CC)CC)N=C1/C(=C/C3C=CC(=CC=3)C(C)C)/CCN1C2=O
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| InChi Key |
GZSNGNPLURZQGM-CJLVFECKSA-N
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| InChi Code |
InChI=1S/C28H35FN4O/c1-5-32(6-2)14-7-13-30-26-18-25-23(17-24(26)29)28(34)33-15-12-22(27(33)31-25)16-20-8-10-21(11-9-20)19(3)4/h8-11,16-19,30H,5-7,12-15H2,1-4H3/b22-16+
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| Chemical Name |
(3E)-6-[3-(diethylamino)propylamino]-7-fluoro-3-[(4-propan-2-ylphenyl)methylidene]-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one
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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 : ~8.33 mg/mL (~18.01 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 | 2.1617 mL | 10.8085 mL | 21.6169 mL | |
| 5 mM | 0.4323 mL | 2.1617 mL | 4.3234 mL | |
| 10 mM | 0.2162 mL | 1.0808 mL | 2.1617 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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