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| Targets |
BV6 TFA targets the inhibitors of apoptosis proteins (IAPs), specifically cIAP1, cIAP2, and XIAP. As a Smac mimetic, it binds to these IAPs, antagonizing their anti-apoptotic function. By binding to cIAPs, BV6 induces their ubiquitination and rapid proteasomal degradation, which leads to the deubiquitination of RIPK1 (receptor-interacting protein kinase 1). This enables RIPK1 to form a necrosome complex, promoting apoptosis and necroptosis in response to death signals such as TNF-alpha.
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| ln Vitro |
BV6 TFA (250 nM-30 μM, 24 h) induced apoptosis in HCC193 and H460 lung cancer cells in a concentration- and time-dependent manner. BV6 TFA also enhanced the sensitivity of HCC193 and H460 cells to radiation [1]. BV6 TFA (1 μM 24 h; 5 μM, 48 h) significantly enhanced the sensitivity of cells to radiation (HCC193: at a concentration of 1 μM BV6, the dose-enhancing ratio DER=1.38; H460: at a concentration of 5 μM BV6, the dose-enhancing ratio DER=1.42) [1].
In vitro, BV6 TFA inhibits the cell viability of HCC193 NSCLC cells with an IC50 of 7.2 uM in MTS assays. It induces apoptosis in both HCC193 and H460 cell lines and significantly enhances the radiosensitivity of these cell lines through activation of cleaved caspase-8 and cleaved caspase-9. In immature dendritic cells, BV6 treatment results in moderate activation of the classical NF-kappaB pathway. BV6 also increases CIK cell-mediated lysis of hematological and solid malignancies. The binding affinity (Kd) is 0.46 nM for cIAP1 and 1.3 nM for XIAP. |
| ln Vivo |
BV6 TFA (10 mg/kg, twice weekly for 4 weeks, intraperitoneal injection) can segment the expression intensity of IAP. BV6 TFA (10 mg/kg, twice weekly for 4 weeks, intraperitoneal injection) can reduce the total number of lesions and the percentage of Ki67 maximal cells compared with the control group.
BV6 TFA can be used in research on endometrial cancer and endometriosis, where IAPs play a role in disease pathogenesis. In vivo, as an IAP antagonist, BV6 would be expected to induce apoptosis in tumor tissues. The compound may be evaluated in xenograft mouse models of NSCLC, endometrial cancer, or other IAP-dependent malignancies. In such studies, BV6 is typically administered intraperitoneally at doses of 10-50 mg/kg. The TFA salt form enhances solubility and stability for in vivo studies. |
| Enzyme Assay |
In vitro IAP binding assay: The binding affinity of BV6 to recombinant human cIAP1 and XIAP is measured by surface plasmon resonance (SPR) or a competitive fluorescence polarization (FP) assay. For SPR, cIAP1 or XIAP is immobilized on a sensor chip, and varying concentrations of BV6 TFA (0.01-1000 nM) are injected. The equilibrium dissociation constant (Kd) is calculated from the steady-state binding responses. For the FP assay, a fluorescent Smac probe is used, and the IC50 is determined.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: HCC193 cells, H460 cells Tested Concentrations: 250 nM, 500 nM, 1 μM, 3 μM, 5 μM, 10 μM, 20 μM, 30 μM Incubation Duration: 24 hours Experimental Results: Decreased cell survival percentage for HCC193 with an IC50 of 7.2μM. Decreased the cell viability of H460 cells by about 60% at 30 μM. Western Blot Analysis[1] Cell Types: HCC193 cells, H460 cells Tested Concentrations: 0.25 μM, 0.5 μM, 1 μM, 5 μM Incubation Duration: 1, 14, 24 hours Experimental Results: Reduced the expression of cIAP1 within one hour and gradually decreased XIAP with increased incubation time for both cell lines. Reduced the expression of cIAP1 with 0.25μM and gradually decreased XIAP with increasing concentration for both cell lines. ELISA Assay[1] Cell Types: HCC193 cells, H460 cells Tested Concentrations: 1 μM, 5 μM Incubation Duration: 12 hours Experimental Results: Induced enhancement of the secretion of TNFα in HCC193 cells. Did not enhance the secretion of TNFα in H460 cells. In vitro cell viability and apoptosis assay: NSCLC cells (HCC193, H460) are seeded in 96-well plates (5,000-10,000 cells/well) in RPMI-1640 with 10% FBS. BV6 TFA is added at concentrations of 0.1-100 uM for 48-72 hours. Cell viability is measured by MTS or CellTiter-Glo assay. The IC50 (7.2 uM for HCC193) is calculated from dose-response curves. Apoptosis is assessed by Annexin V-FITC/PI flow cytometry and by measuring caspase-3/7 activity. Radiosensitization is assessed by clonogenic survival assays after ionizing radiation (2-10 Gy). |
| Animal Protocol |
Animal/Disease Models: Female endometriosis mice modeling by Estradiol valerate at the dosage 0.5 µg/mouse/week s.c injected (6 weeks of age, BALB/c).
Doses: 10 mg/kg Route of Administration: a single i.p. injection,twice weekly for 4 weeks Experimental Results: Attenuated the intensity of IAPs expression. In vivo xenograft mouse model for NSCLC: Female BALB/c nude mice (6-8 weeks old) are subcutaneously inoculated with 5×10⁶ HCC193 or H460 cells in 0.1 mL PBS/Matrigel (1:1). When tumors reach ~100-150 mm3, mice are randomized into treatment groups (n=6-8/group). BV6 TFA is formulated in a suitable vehicle (e.g., 10% DMSO + 5% Tween 80 + 85% saline) and administered intraperitoneally at doses of 10-50 mg/kg once daily for 2-3 weeks. Control groups receive vehicle alone. Tumor volume is measured every 2-3 days with calipers. At endpoint, tumors are excised and processed for histology (H&E staining), immunohistochemistry (cleaved caspase-3 for apoptosis), and Western blotting for cIAP1, XIAP, and cleaved PARP. |
| ADME/Pharmacokinetics |
No specific PK data for BV6 TFA is available. As a bivalent Smac mimetic (MW of free base: 1205.57 Da), it is not orally bioavailable due to its high molecular weight and hydrophilicity. For in vivo studies, BV6 is typically administered intraperitoneally. The TFA salt form is used to enhance solubility. The half-life in rodents is expected to be short (< 2-4 h) due to rapid clearance. The compound is metabolically stable due to its peptide-like structure but may be subject to proteolysis in vivo. For research use, it is formulated in DMSO/PEG300/Tween 80/saline.
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| Toxicity/Toxicokinetics |
For BV6 TFA, hazard statements: H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation). Signal word: Warning. Precautionary statements: P261 (Avoid breathing dust/fume/gas/mist/vapors/spray), P280 (Wear protective gloves/protective clothing/eye protection/face protection), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes). Storage: lyophilized powder at -20degC, protected from light and moisture. Handle in a fume hood with appropriate PPE. For research use only.
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| References |
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| Additional Infomation |
BV6 TFA is a research-grade bivalent Smac mimetic and a potent antagonist of cIAP1, cIAP2, and XIAP (Kds: 0.46 and 1.3 nM). It is used as a tool to study apoptosis, necroptosis, and IAP biology in cancer research. It is not an FDA-approved drug. For research use only, not for diagnostic or therapeutic applications. The compound is for research use only (RUO).
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| Molecular Formula |
C70H96N10O8.XC2HF3O2
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| Molecular Weight |
1205.57 (free base)
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| Related CAS # |
BV6; 1001600-56-1
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| Appearance |
Solid powder
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| SMILES |
C[C@@H](C(=O)N[C@@H](C1CCCCC1)C(=O)N2CCC[C@H]2C(=O)N[C@@H](C(C3=CC=CC=C3)C4=CC=CC=C4)C(=O)NCCCCCCNC(=O)[C@H](C(C5=CC=CC=C5)C6=CC=CC=C6)NC(=O)[C@@H]7CCCN7C(=O)[C@H](C8CCCCC8)NC(=O)[C@H](C)NC)NC
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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.) |
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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