Abstract
Multiple myeloma (MM) is an incurable neoplasm characterized by devastating and progressive bone destruction. Standard chemotherapeutic agents have not been effective at significantly prolonging the survival of MM patients and these agents are typically associated with often severe, dose-limiting side effects. There is great need for methods to target the delivery of novel, effective cytotoxic agents specifically to bone, where myeloma cells reside. We have synthesized and evaluated the effects of the bone-targeted proteasome inhibitors PS-341-BP-1, PS-341-BP-2 and MG-262-BP on cell proliferation using the mouse 5TGM1 and human RPMI 8226 cell lines in vitro. The compounds exhibit strong cytotoxicity on MM cell lines and reduce the number of viable cells in a dose dependent manner.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 6455-6458 |
| Number of pages | 4 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 23 |
| Issue number | 23 |
| DOIs | |
| State | Published - Dec 1 2013 |
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Keywords
- Bisphosphonate conjugate
- Bone-targeted
- Boronic acid
- Multiple myeloma
- Proteasome inhibitor
ASJC Scopus subject areas
- Pharmaceutical Science
- Drug Discovery
- Organic Chemistry
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry
- Biochemistry
Cite this
Design, synthesis, and biological evaluation of bone-targeted proteasome inhibitors for multiple myeloma. / Agyin, Joseph K.; Santhamma, Bindu; Roy, Sudipa S.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 23, 01.12.2013, p. 6455-6458.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Design, synthesis, and biological evaluation of bone-targeted proteasome inhibitors for multiple myeloma
AU - Agyin, Joseph K.
AU - Santhamma, Bindu
AU - Roy, Sudipa S.
PY - 2013/12/1
Y1 - 2013/12/1
N2 - Multiple myeloma (MM) is an incurable neoplasm characterized by devastating and progressive bone destruction. Standard chemotherapeutic agents have not been effective at significantly prolonging the survival of MM patients and these agents are typically associated with often severe, dose-limiting side effects. There is great need for methods to target the delivery of novel, effective cytotoxic agents specifically to bone, where myeloma cells reside. We have synthesized and evaluated the effects of the bone-targeted proteasome inhibitors PS-341-BP-1, PS-341-BP-2 and MG-262-BP on cell proliferation using the mouse 5TGM1 and human RPMI 8226 cell lines in vitro. The compounds exhibit strong cytotoxicity on MM cell lines and reduce the number of viable cells in a dose dependent manner.
AB - Multiple myeloma (MM) is an incurable neoplasm characterized by devastating and progressive bone destruction. Standard chemotherapeutic agents have not been effective at significantly prolonging the survival of MM patients and these agents are typically associated with often severe, dose-limiting side effects. There is great need for methods to target the delivery of novel, effective cytotoxic agents specifically to bone, where myeloma cells reside. We have synthesized and evaluated the effects of the bone-targeted proteasome inhibitors PS-341-BP-1, PS-341-BP-2 and MG-262-BP on cell proliferation using the mouse 5TGM1 and human RPMI 8226 cell lines in vitro. The compounds exhibit strong cytotoxicity on MM cell lines and reduce the number of viable cells in a dose dependent manner.
KW - Bisphosphonate conjugate
KW - Bone-targeted
KW - Boronic acid
KW - Multiple myeloma
KW - Proteasome inhibitor
UR - http://www.scopus.com/inward/record.url?scp=84886951236&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84886951236&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2013.09.043
DO - 10.1016/j.bmcl.2013.09.043
M3 - Article
C2 - 24119559
AN - SCOPUS:84886951236
VL - 23
SP - 6455
EP - 6458
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 23
ER -