Delanzomib (CEP-18770)

Cas：847499-27-8

Product Information：

Delanzomib, also known as CEP-18770, is An orally bioavailable synthetic P2 threonine boronic acid inhibitor of the chymotrypsin-like activity of the proteasome, with potential antineoplastic activity. Proteasome inhibitor CEP 18770 represses the proteasomal degradation of a variety of proteins, including inhibitory kappaBalpha (IkappaBalpha), resulting in the cytoplasmic sequestration of the transcription factor NF-kappaB; inhibition of NF-kappaB nuclear translocation and transcriptional up-regulation of a variety of cell growth-promoting factors; and apoptotic cell death in susceptible tumor cell populations.

Chemical Formula: C21H28BN3O5

Exact Mass: 413.2122

Molecular Weight: 413.27

Elemental Analysis: C, 61.03; H, 6.83; B, 2.62; N, 10.17; O, 19.36

Synonym:

CEP18770

CEP 18770

CEP-18770

Chemical Name: [(1R)-1-[[(2S,3R)-3-Hydroxy-2-[[(6-phenylpyridin-2-yl)carbonyl]amino]-1-oxobutyl]amino]-3-methylbutyl]boronic acid.

InChi Key: 

SJFBTAPEPRWNKH-CCKFTAQKSA-N

InChi Code: InChI=1S/C21H28BN3O5/c1-13(2)12-18(22(29)30)24-21(28)19(14(3)26)25-20(27)17-11-7-10-16(23-17)15-8-5-4-6-9-15/h4-11,13-14,18-19,26,29-30H,12H2,1-3H3,(H,24,28)(H,25,27)/t14-,18+,19+/m1/s1

Smiles Code:

CC(C)C[C@@H](B(O)O)NC([C@@H](NC(C1=NC(C2=CC=CC=C2)=CC=C1)=O)[C@H](O)C)=O

Technical Data：

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

In Vitro:

Delanzomib (CEP-18770; 20 nM; 12-24 hours) treatment results in a progressive appearance of cleaved caspases-3, -7, and -9 between 12 and 24 hours’exposure in the human MM cell lines, RPMI-8226, and U266.

Delanzomib (CEP-18770; 5-40 nM; 4-24 hours) treatment induces an accumulation of ubiquitinated proteins over 4 to 8 hours.

Delanzomib (CEP-18770) inhibits endothelial cell survival, vasculogenesis, and osteoclastogenesis in vitro; and displays a favorable cytotoxicity profile toward normal cells.

In Vivo:

Delanzomib (CEP-18770; 7.8-13 mg/kg; oral administration; twice a week; for 4 weeks) treatment results in a more sustained pharmacodynamic inhibition of proteasome activity in tumors relative to normal tissues, complete tumor regression of multiple myeloma (MM) xenografts and improves overall median survival in a systemic model of human MM.

References：

1. Fuchs, Ota. Proteasome inhibition as a therapeutic strategy in patients with multiple myeloma. Multiple Myeloma (2009), 101-125. CODEN: 69MVM2 AN 2010:737549

2. Genin, E.; Reboud-Ravaux, M.; Vidal, J. Proteasome inhibitors: recent advances and new perspectives in medicinal chemistry. Current Topics in Medicinal Chemistry (Sharjah, United Arab Emirates) (2010), 10(3), 232-256. CODEN: CTMCCL ISSN:1568-0266. CAN 152:516315 AN 2010:423458

3. Sanchez, Eric; Li, Mingjie; Steinberg, Jeffrey A.; Wang, Cathy; Shen, Jing; Bonavida, Benjamin; Li, Zhi-Wei; Chen, Haiming; Berenson, James R. The proteasome inhibitor CEP-18770 enhances the anti-myeloma activity of bortezomib and melphalan. British Journal of Haematology (2010), 148(4), 569-581. CODEN: BJHEAL ISSN:0007-1048. AN 2010:353952

4. Dick, Lawrence R.; Fleming, Paul E. \Building on bortezomib: second-generation proteasome inhibitors as anti-cancer therapy. Drug Discovery Today (2010), 15(5/6), 243-249. CODEN: DDTOFS ISSN:1359-6446. AN 2010:318415

5. Ruggeri, Bruce; Miknyoczki, Sheila; Dorsey, Bruce; Hui, Ai-Min. The development and pharmacology of proteasome inhibitors for the management and treatment of cancer. Advances in Pharmacology (San Diego, CA, United States) (2009), 57(Contemporary Aspects of Biomedical Research: Drug Discovery), 91-135. CODEN: ADPHEL ISSN:1054-3589. AN 2010:62762

Products are for research use only. Not for human use.