ONO-5334

Category	SARS-CoV
CAS	868273-90-9
Description	NO-5334 is cathepsin K inhibitor Ki values of 0.1 nM for human. It can improve bone strength by preferentially increasing cortical bone mass in ovariectomized rats. ONO-5334 can also inhibit N-terminal and C-terminal collagen crosslinks in serum and urine in postmenopausal women. In Feb 2012, Phase-II for Osteoporosis in European Union was discontinued.

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Product Information

Synonyms	ONO-5334; ONO 5334; ONO5334. N-((S)-3-(2-((R,Z)-3,4-dimethylthiazolidin-2-ylidene)hydrazinyl)-2,3-dioxo-1-(tetrahydro-2H-pyran-4-yl)propyl)cycloheptanecarboxamide
IUPAC Name	N-[(1S)-3-[(2Z)-2-[(4R)-3,4-dimethyl-1,3-thiazolidin-2-ylidene]hydrazinyl]-1-(oxan-4-yl)-2,3-dioxopropyl]cycloheptanecarboxamide
Molecular Weight	438.59
Molecular Formula	C21H34N4O4S
Canonical SMILES	O=C(N/N=C1SC[C@@H](C)N\1C)C([C@@H](NC(C2CCCCCC2)=O)C3CCOCC3)=O
InChI	InChI=1S/C21H34N4O4S/c1-14-13-30-21(25(14)2)24-23-20(28)18(26)17(15-9-11-29-12-10-15)22-19(27)16-7-5-3-4-6-8-16/h14-17H,3-13H2,1-2H3,(H,22,27)(H,23,28)/b24-21-/t14-,17+/m1/s1
InChIKey	BTZCSXIUAFVRTE-CHGLIHOBSA-N
Purity	98%
Density	1.4±0.1 g/cm3
Solubility	Soluble in DMSO
Appearance	Powder
Application	Osteoporosis
Shelf Life	2 month in rt, long time
Storage	-20°C Freezer
Complexity	657
Exact Mass	438.23007675
Index Of Refraction	1.644
In Vitro	ONO-5334 has inhibitory effects on human cathepsin S, human cathepsin L, human cathepsin B, porcine calpain Ι and porcine calpain II with Ki values of 0.83 nM, 1.7 nM, 32 nM, 82 nM and 69 nM, respectively. ONO-5334 (0.1-1 μM; 24 hours) suppresses human osteoclast-mediated bone resorption. It potently reduces osteoclast-mediated release of CTX from bone slices as a dose dependent manner. ONO-5334 (0-10 μM; pre-treated for 16 h) inhibits antiviral activities in a discernable dose-dependent manner in Vero E6 cells by designed to capture multicycle replication, exhibiting an EC50 value of 0.5 μM).
In Vivo	ONO-5334 (oral administration; 0.12-15 mg/kg; single dose) can dose-dependently reduce PTHrP-induced increase in plasma calcium with significant effect (86% reduction) at 15 mg/kg. It also reduces PTHrP-induced increase in plasma CTX level in TPTX rats by 90% at 15 mg/kg. ONO-5334 (oral administration; 0.3-30 mg/kg; 7 consecutive days) at 3 mg/kg or 30 mg/kg significantly decreases CTX (a bone resorption marker) concentration. On day 7, the reduction in serum CTX concentration by ONO-5334 at 3 mg/kg and 30 mg/kg was 62% and 79%, respectively.
Target	Ki: 0.10 nM (human cathepsin K) Ki: 0.049 nM (rabbit cathepsin K) Ki: 0.85 nM (rat cathepsin K)
XLogP3-AA	3.1