BV6

SKU: orb1227183

Description

A small molecule, bivalent IAP antagonist that binds to the c-IAP1 and XIAP BIR2-BIR3 domains with Kd of 0.46 and 0.029 nM, respectively; results in dramatic induction of auto-ubiquitination activity and rapid proteasomal degradation of c-IAPs; also induces induce TNFα-dependent cell death, exhibits single-agent cell killing activity in EVSA-T cell line (IC50=14 nM).

Key Properties

• CAS Number: 1001600-56-1
• MW: 1205.573
• Purity: >98% (HPLC)
• Formula: C₇₀H₉₆N₁₀O₈
• SMILES: O=C([C@H]1N(C([C@H](C2CCCCC2)NC([C@@H](NC)C)=O)=O)CCC1)N[C@@H](C(C3=CC=CC=C3)C4=CC=CC=C4)C(NCCCCCCNC([C@@H](NC([C@H]5N(C([C@H](C6CCCCC6)NC([C@@H](NC)C)=O)=O)CCC5)=O)C(C7=CC=CC=C7)C8=CC=CC=C8)=O)=O
• Target: IAP
• Solubility: DMSO: ≥ 58 mg/mL

Bioactivity

• In 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. The size of lesions range from ~2 to 7 mm in diameter. The monolayer epithelial cell lining of the cyst is shown. After immunohistochemical staining, cytokeratin and vimentin are positively stained, whereas calretinin is negative. After BV6 treatment for 4 weeks, the total number of lesions (4.6 versus 2.8/mouse), the average weight (78.1 versus 32.0 mg/mouse) and the surface area (44.5 versus 24.6 mm2/mouse) of lesions are significantly less than in the controls. In the endometrial gland epithelia or stroma, the percentage of Ki67-positive cells decreases after BV6 treatment.
• In Vitro:
  HCC193 has an IC50 of 7.2 μM in MTS assays, while H460 cells are not reduced to 50% viability even with 30 μM BV6 treatment. Administration of 1 μM BV6 to HCC193 cells induces complete depletion of cIAP1 levels at 1 hour post-treatment, while a decrease in XIAP levels is not seen until 24 hours following addition of drug. Similarly, 5 μM BV6 fully depletes cIAP1 at 1 hour and begin to reduce XIAP at 24 hours in H460 cells. In parallel findings, cIAP1 levels are decreased in response to a small dose of 0.25 μM BV6 in both cell lines, whereas trace amounts of XIAP are still present at 5 μM BV6. HCC193 cells demonstrates noticeable cleaved caspase-3 levels beginning 12 hours post-incubation with 1 μM BV6, and cleaved caspase-3 levels continued to increase in a time-dependent manner over 48 hours. Treatment of HCC193 cells with 1 μM BV6 for 24 hours causes a significant survival curve shift in HCC193 cells relative to DMSO-treated cells, with a DER=1.38 (p<0.05). BV6 (2 and 5 μM) significantly represses BrdU incorporation in ectopic and eutopic (disease-free and myomas) ESCs. An ~30% decrease of BrdU incorporation is observed in both groups after treatment with 5 μM BV6.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

BV 6 | BV-6

Quick Database Links

Gene Symbol

IAP