| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg | |||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Bcl2-BH4 (Ki = 3.3 nM)
BCL-2 BH4 domain (Ki = 3.3 nM) |
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| ln Vitro |
BDA-366 triggers a conformational change in BCL2, which causes strong apoptosis in primary and MM(Multiple Myeloma) cell lines. Lung cancer cell growth is inhibited both in vitro and in vivo by BDA-366, which causes a conformational change in the BCL2 molecule that changes it into a death protein[1]. As evidence of the exclusivity of its Bcl2 binding, BDA-366 did not bind to other Bcl2 family members, such as Bcl-XL, Mcl-1, or Bfl-1/A1. Calcium (Ca2+) release is induced by BDA-366 by inhibiting the interaction between Bcl2/IP3R and apoptotic cells in a Bax-dependent manner[2].
BDA-366 binds to the BCL-2 BH4 domain with high affinity (Ki = 3.3 ± 0.73 nM) and selectivity, showing no binding to other Bcl-2 family members including Bcl-XL, Mcl-1, or Bfl-1/A1. It induces a conformational change in the BCL-2 molecule that nullifies its anti-apoptotic function and transforms it into a pro-apoptotic entity. BDA-366 induces robust apoptosis in multiple myeloma cell lines and primary MM cells, and inhibits lung cancer cell growth. The compound has also been shown to inhibit extra-nodal natural killer/T-cell lymphoma by inducing mitochondria damage through the NF-κB pathway. However, some studies have questioned the specificity of BDA-366, suggesting that it may induce apoptosis independently of BCL-2 in a variety of cancer cell models. |
| ln Vivo |
Delivery of BDA-366 significantly reduced the growth of human MM xenografts in NOD-scid/IL2Rγ null mice while having minimal cytotoxic effects on body weight or normal hematopoietic cells[1].
Additionally, in animal models, BDA-366 inhibits the growth of lung cancer by inducing apoptosis. In vivo testing of the BH4 antagonist BDA-366 against human lung cancer demonstrates potent efficacy without platelet reduction[2]. BDA-366 significantly inhibits tumor growth in vivo in multiple models. In Nu/Nu nude mice bearing lung cancer xenografts, intraperitoneal administration at 10–50 mg/kg/day for 14 days induces apoptosis and potently inhibits tumor growth in a dose-dependent manner. In NSG mice with human MM cells, BDA-366 treatment inhibits tumor growth. BDA-366 also inhibits ENKTL tumor growth in vivo with no obvious cytotoxicity to normal hematopoietic cells. The compound's ability to inhibit tumor growth across multiple cancer types, including lung cancer, multiple myeloma, and ENKTL, supports its potential as a broad-spectrum anticancer agent. |
| Enzyme Assay |
BDA-366 is a potent and selective small-molecule antagonist of the Bcl2-BH4 domain, it binds to BH4 with high affinity and selectivity. The antiapoptotic function of Bcl2 is dependent on the BH4 domain, making it a promising anticancer target. BCL2's prosurvival function was lost when BDA-366 caused a conformational change that exposed the BH3 domain, turning BCL2 into a prodeath protein. BDA-366 binds to BCL2 with high affinity in both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cells. By activating BAX and releasing cytochrome c in a BCL2-dependent manner, BDA-366 induced apoptosis. BDA-366 decreased Bcl2/IP3R binding in H460 cells, which led to an increase in Ca2+ release.
Binding affinity to BCL-2 BH4 domain is measured using surface plasmon resonance or fluorescence polarization assays to determine the Ki value of 3.3 nM. Selectivity profiling is conducted against other Bcl-2 family members including Bcl-XL, Mcl-1, and Bfl-1/A1 using similar binding assays to confirm specificity. The binding of BDA-366 with the BH4 domain results in conversion of BCL-2 from an antiapoptotic molecule into a death protein through a conformational change that exposes its BH3 death domain. |
| Cell Assay |
BDA366 was applied to the human MM cell lines RPMI8226 and U266 for 48 hours at progressively higher concentrations (0, 0.1, 0.25, 0.5μM). After being collected, the cells were stained with Annexin V and PI and then analyzed using FACS. On the population of Annexin V-positive cells, apoptotic cells were gated. Early apoptotic cells were identified as Annexin V+PI+, late apoptotic cells as Annexin+PI+, and necrotic cells as AnnexinPI+.
Apoptosis induction is assessed in multiple myeloma cell lines and primary MM cells using flow cytometry with annexin V/PI staining. Cell viability is measured using MTT or CellTiter-Glo assays. BCL-2 conformational change is detected using conformation-specific antibodies or immunoprecipitation. Effects on mitochondrial membrane potential and ROS levels are measured using fluorescent dyes. The compound's ability to induce mitochondria damage through the NF-κB pathway is also assessed. |
| Animal Protocol |
Dissolved in DMSO, diluted in PBS; 10 mg/kg; i.p.
NSG mice In lung cancer xenograft models, Nu/Nu nude mice are treated with increasing doses of BDA-366 (10–50 mg/kg/day) via intraperitoneal injection for 14 days. In NSG mice with human MM cells, five doses of BDA-366 or DMSO are administered on days 0, 2, 4, 6, and 8. Tumor growth inhibition, apoptosis induction, and toxicity to normal cells are assessed. The compound is formulated for in vivo administration using appropriate vehicles. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for BDA-366 are limited. In vivo efficacy studies have been conducted using intraperitoneal administration at doses ranging from 10–50 mg/kg/day. The compound is soluble in DMSO for formulation. Detailed PK parameters such as half-life, bioavailability, and tissue distribution have not been extensively reported in the available literature. The compound can be formulated for oral administration using homogeneous suspension in CMC-Na or clear solution in DMSO/PEG300/Tween 80/ddH2O.
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| Toxicity/Toxicokinetics |
In preclinical studies, BDA-366 shows no obvious cytotoxicity to normal hematopoietic cells at efficacious doses. Comprehensive toxicology data are limited as the compound remains in preclinical development. Standard laboratory safety precautions should be observed during handling, and the compound should be considered for research use only. The compound has not been evaluated in formal toxicology studies for human use.
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| References | |
| Additional Infomation |
BDA-366 belongs to the anthraquinone class of compounds, with the structure 1,4-diamino-9,10-anthraquinone, where the two amino groups are substituented with 3-(diethylamino)-2-hydroxypropyl and (ethylene oxide-2-yl)methyl groups, respectively. It possesses anticancer activity and can be used as an antitumor drug and an apoptosis inducer. BDA-366 is an anthraquinone, epoxide, tertiary amine, secondary amine, and secondary alcohol compound, with functions similar to 9,10-anthraquinone.
BDA-366 represents a novel therapeutic approach targeting the BH4 domain of BCL-2, distinct from BH3-mimetics like venetoclax (ABT-199). It has shown potent anti-tumor effects in multiple myeloma, lung cancer, and ENKTL models. The compound induces mitochondria-mediated apoptosis through suppression of NF-κB signaling. BDA-366 has not entered clinical trials and remains a research tool for studying BCL-2 biology and cancer therapy. However, some studies have questioned the specificity of BDA-366, suggesting that it may induce apoptosis independently of BCL-2 in a variety of cancer cell models. Further research is needed to fully elucidate its mechanism of action and therapeutic potential. |
| Molecular Formula |
C24H29N3O4
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| Molecular Weight |
423.5
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| Exact Mass |
435.215
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| CAS # |
1821496-27-8
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| Related CAS # |
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| PubChem CID |
91826545
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
705.4±60.0 °C at 760 mmHg
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| Flash Point |
380.4±32.9 °C
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| Vapour Pressure |
0.0±2.4 mmHg at 25°C
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| Index of Refraction |
1.681
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
31
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| Complexity |
640
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O1C([H])([H])[C@]1([H])C([H])([H])N([H])C1C([H])=C([H])C(=C2C(C3=C([H])C([H])=C([H])C([H])=C3C(C=12)=O)=O)N([H])C([H])([H])[C@@]([H])(C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])[H])O[H]
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| InChi Key |
JYOOEVFJWLBLKF-HOTGVXAUSA-N
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| InChi Code |
InChI=1S/C24H29N3O4/c1-3-27(4-2)13-15(28)11-25-19-9-10-20(26-12-16-14-31-16)22-21(19)23(29)17-7-5-6-8-18(17)24(22)30/h5-10,15-16,25-26,28H,3-4,11-14H2,1-2H3/t15-,16-/m0/s1
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| Chemical Name |
1-[[(2S)-3-(diethylamino)-2-hydroxypropyl]amino]-4-[[(2S)-oxiran-2-yl]methylamino]anthracene-9,10-dione
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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 | 2.3613 mL | 11.8064 mL | 23.6128 mL | |
| 5 mM | 0.4723 mL | 2.3613 mL | 4.7226 mL | |
| 10 mM | 0.2361 mL | 1.1806 mL | 2.3613 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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