SNIPER(TACC3)-1

Size	Price	Stock	Quantity
--	$--	In stock

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

Soluble in DMSO

Appearance

Solid Powder

Storage

Store at 2-8°C for short term (days to weeks) or -20°C for long term (months to years)

Shipping

Room temperature in continental US; may vary elsewhere

IUPACName

N-[2-[2-[2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoyl]amino]ethoxy]ethoxy]ethyl]-4-[4-[[[4-(2-methylpropylamino)pyrimidin-2-yl]amino]methyl]-1,3-thiazol-2-yl]benzamide

Synonyms

N-((11S,14S,15R)-15-amino-14-hydroxy-11-isobutyl-10,13-dioxo-16-phenyl-3,6-dioxa-9,12-diazahexadecyl)-4-(4-(((4-(isobutylamino)pyrimidin-2-yl)amino)methyl)thiazol-2-yl)benzamide

Density

1.3±0.1 g/cm3

InChI Key

CMKAAFQRJONAAN-ZHAMFGDSSA-N

InChI

InChI=1S/C41H57N9O6S/c1-27(2)22-34(49-39(54)36(51)33(42)23-29-8-6-5-7-9-29)38(53)44-17-19-56-21-20-55-18-16-43-37(52)30-10-12-31(13-11-30)40-48-32(26-57-40)25-47-41-45-15-14-35(50-41)46-24-28(3)4/h5-15,26-28,33-34,36,51H,16-25,42H2,1-4H3,(H,43,52)(H,44,53)(H,49,54)(H2,45,46,47,50)/t33-,34+,36+/m1/s1

Canonical SMILES

CC(C)CC(C(=O)NCCOCCOCCNC(=O)C1=CC=C(C=C1)C2=NC(=CS2)CNC3=NC=CC(=N3)NCC(C)C)NC(=O)C(C(CC4=CC=CC=C4)N)O

1. SNIPER(TACC3) induces cytoplasmic vacuolization and sensitizes cancer cells to Bortezomib.

Ohoka, N., Nagai, K., Shibata, N., Hattori, T., Nara, H., Cho, N. and Naito, M., 2017. Cancer science, 108(5), pp.1032-1041.

We previously developed a hybrid small molecule SNIPER (Specific and Nongenetic IAP-dependent Protein ERaser) against transforming acidic coiled-coil-3 (TACC3), SNIPER(TACC3), that induces proteasomal degradation of TACC3 protein. In this study, we found that SNIPER(TACC3) induces cytoplasmic vacuolization derived from endoplasmic reticulum (ER) and paraptosis-like cell death selectively in cancer cells. Mechanistic analysis suggests that accumulation of ubiquitylated protein aggregates that requires X-linked inhibitor of apoptosis protein (XIAP) induces ER stress, which results in ER-stress responses involving X-box binding protein-1 (XBP-1) and ER-derived vacuolization in cancer cells. Importantly, inhibition of proteasome enhanced the SNIPER(TACC3)-induced vacuolization, and the combination treatment of SNIPER(TACC3) and bortezomib exhibited a synergistic anticancer activity in several cancer cell lines. The induction of paraptosis-like cell death in cancer cells by SNIPER(TACC3) could be applied to treat cancer cells resistant to undergo apoptosis by overexpression of XIAP.

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