BV-6

Alias: Smac mimetic BV6; BV6; BV-6; BV 6
Cat No.:V0055 Purity: ≥98%
BV-6 is a novel and potent SMAC (second mitochondrial-derived activator of caspases)mimetic, and a dual inhibitor of cIAP (inhibitor of apoptosis) and XIAP (X-linked inhibitor of apoptosis) with potential anticancer activity.
BV-6 Chemical Structure CAS No.: 1001600-56-1
Product category: IAP
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

BV-6 is a novel and potent SMAC (second mitochondrial-derived activator of caspases) mimetic, and a dual inhibitor of cIAP (inhibitor of apoptosis) and XIAP (X-linked inhibitor of apoptosis) with potential anticancer activity. It works by stimulating the differentiation of glioblastoma cancer stem cells by turning on NF-κB.

Biological Activity I Assay Protocols (From Reference)
Targets
cIAP; XIAP
ln Vitro
Inducing apoptosis in both HCC193 and H460 cell lines, BV6 also significantly increases the radiosensitivity of these cell lines by activating cleaved caspase-8 and cleaved caspase-9, respectively. BV6 inhibits the cell viability of HCC193 NSCLC cells with an IC50 of 7.2 μM. [1]
The traditional NF-kB pathway is moderately activated in immature dendritic cells after BV-6 treatment.[2]
Additionally, BV-6 increases the CIK cell-mediated lysis of solid malignancies (RH1, RH30, and TE671) as well as hematological malignancies (H9, THP-1, and Tanoue). Additionally, BV-6 increases the apoptosis of peripheral blood mononuclear cells and, most significantly, inhibits immune cells, reducing their capacity for cytotoxicity.[3]
ln Vivo
Murine cIAP-1, cIAP-2 and XIAP expressions are clearly observed in the cytoplasm of both epithelial and stromal cells of implants, whereas Survivin is mainly expressed in the nuclei BV6 treatment for 4 weeks attenuated the intensity of IAPs expression. Lesions can be anywhere between 2 and 7 mm in diameter. The cyst's monolayer epithelial cell lining is visible. Vimentin and cytokeratin are positively stained after immunohistochemical staining, but calretinin is negatively stained. The total number of lesions (4.6 versus 2.8/mouse), average weight (78.1 versus 32.0 mg/mouse), and surface area (44.5 versus 24.6 mm2/mouse) of lesions are all significantly lower than in the control group after 4 weeks of BV6 treatment. In the endometrial gland epithelia or stroma, the percentage of Ki67-positive cells decreases after BV6 treatment.
Cell Assay
The CellTiter 96® Aqueous Non-Radioactive Cell Proliferation Assay kit is used to assess cell viability. In triplicate, 96-well plates are seeded with 5000 cells per well. Different wells are then filled with BV6 in varying concentrations after the cells have adhered to them. The same amount of DMSO is administered to the control groups. 24 hours later, the final doses of 333 μg/mL MTS and 25 μM PMS are added to each well. Plates are read at 490 nm on a microplate reader after two hours of incubation at 37 °C in humidified 5% CO2. By comparing the absorbance of each sample to that of the corresponding control, one can determine the relative cell viability of each one. Using Prism 5.01, the IC50 values are determined. Cells are exposed to 1 and 5 μM BV6 with or without 10 μg/mL infliximab for the TNFα-neutralizing antibody assay, which is then conducted 24 hours later. Using a microplate reader, plates are read at 490 nm absorbance.
Animal Protocol
10 mg/kg; i.p.
Mice: Female mice (6 weeks of age, BALB/c) are used. All 24 mice are ovariectomized through a 1 cm longitudinal skin incision then injected s.c. with estradiol valerate (0.5 μg/mouse/week) once per week for 6 weeks until the experimental endometriosis induction. Two weeks after ovariectomy, the uteri of an additional eight donor mice (n=8) are removed en bloc after euthanasia and cleaned of excess tissue in sterile saline. Each uterus is cut to include the uterine horns in each half with a linear incision longitudinally and minced (0.5 mm in diameter) with dissecting scissors. The ovariectomized recipient mice (n=16) are anesthetized using pentobarbital sodium. A 0.5 cm subabdominal midline incision is made. Each recipient receives half of the donor uterus (1:2 donor uterus to host ratio) minced and added to 500 μl saline, and injected into the peritoneal cavity, and the peritoneum is sutured. Injected uterine tissue weighed ~50 mg per mouse. For the next 4 weeks, recipient mice are treated with a single i.p. injection of BV6 (n=8; 10 mg/kg) or vehicle (n=8; 1% DMSO) twice weekly.
References

[1]. J Thorac Oncol . 2011 Nov;6(11):1801-9.

[2]. PLoS One . 2011;6(6):e21556.

[3]. Front Pediatr . 2014 Jul 18:2:75.

[4]. Hum Reprod . 2015 Jan;30(1):149-58.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C70H96N10O8
Molecular Weight
1205.57
Exact Mass
1,204.74
Elemental Analysis
C, 69.74; H, 8.03; N, 11.62; O, 10.62
CAS #
1001600-56-1
Related CAS #
1001600-56-1(free base)
Appearance
A crystalline solid
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
InChi Key
DPXJXGNXKOVBJV-YLOPQIBLSA-N
InChi Code
InChI=1S/C70H96N10O8/c1-47(71-3)63(81)75-59(53-37-21-11-22-38-53)69(87)79-45-27-41-55(79)65(83)77-61(57(49-29-13-7-14-30-49)50-31-15-8-16-32-50)67(85)73-43-25-5-6-26-44-74-68(86)62(58(51-33-17-9-18-34-51)52-35-19-10-20-36-52)78-66(84)56-42-28-46-80(56)70(88)60(54-39-23-12-24-40-54)76-64(82)48(2)72-4/h7-10,13-20,29-36,47-48,53-62,71-72H,5-6,11-12,21-28,37-46H2,1-4H3,(H,73,85)(H,74,86)(H,75,81)(H,76,82)(H,77,83)(H,78,84)/t47-,48-,55-,56-,59-,60-,61-,62-/m0/s1
Chemical Name
(2S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-[(2S)-1-[6-[[(2S)-2-[[(2S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]pyrrolidine-2-carbonyl]amino]-3,3-diphenylpropanoyl]amino]hexylamino]-1-oxo-3,3-diphenylpropan-2-yl]pyrrolidine-2-carboxamide
Synonyms
Smac mimetic BV6; BV6; BV-6; BV 6
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 Data
Solubility (In Vitro)
DMSO: ~100 mg/mL (~82.9 mM)
Water: ~25 mg/mL (~20.7 mM)
Ethanol: ~100 mg/mL (~82.9 mM)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 0.8295 mL 4.1474 mL 8.2948 mL
5 mM 0.1659 mL 0.8295 mL 1.6590 mL
10 mM 0.0829 mL 0.4147 mL 0.8295 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.

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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.

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Biological Data
  • BV-6
    SMAC mimetic BV6 induces cell death in monocytes.


    SMAC mimetic BV6 induces cell death in monocytes.

  • BV-6
    Müller-Sienerth N, et al. PLoS One. 2011, 6(6), e21556
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