RA190

Research use only, not for human use.

RA190 (RA-190) is a reversible, highly selective, orally active inhibitor of the proteasomal ubiquitin receptor Rpn13.

RA190 (RA-190) is a reversible, highly selective, orally active inhibitor of the proteasomal ubiquitin receptor Rpn13, exhibits potent anti-proliferative effects against MM lines (IC50<0.1 uM) and HPV-transformed cells (IC50<0.3 uM); inhibits proteasome function, triggering rapid accumulation of polyubiquitinated proteins; profoundly reduced growth of MM and ovarian cancer xenografts.

RA190 covalently binds to cysteine 88 of ubiquitin receptor RPN13 in the 19S regulatory particle and inhibits proteasome function, triggering rapid accumulation of polyubiquitinated proteins. Multiple myeloma (MM) lines, even those resistant to bortezomib, are sensitive to RA190 via endoplasmic reticulum stress-related apoptosis. RA190 stabilizes targets of human papillomavirus (HPV) E6 oncoprotein, and preferentially kills HPV-transformed cells.

RA190 distributes to plasma and major organs excepting brain, and inhibits proteasome function in skin and muscle. RA190 administration profoundly reduces growth of multiple myeloma and ovarian cancer xenografts, and oral RA190 treatment retards HPV16+ syngeneic mouse tumor growth, without impacting spontaneous HPV-specific CD8+ T cell responses.

RA-190 | RA 190

Proteasome/Ubiquitin

Proteasome

Proteasome

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1617495-03-0

596.7594

C28H23Cl5N2O2

>98% (HPLC)

DMSO: 10 mM

C1C(=CC2=CC(=C(C=C2)Cl)Cl)C(=O)C(=CC3=CC(=C(C=C3)Cl)Cl)CN1C(=O)C(CC4=CC=CC=C4)N.Cl

4-Piperidinone, 1-[(2S)-2-amino-1-oxo-3-phenylpropyl]-3,5-bis[(3,4-dichlorophenyl)methylene]-, hydrochloride (1:1)

(-20℃)

With Ice Pack

≥ 2 years