Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C21H28BN3O5 |
| Molecular Weight | 413.275 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 3 / 3 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)C[C@H](NC(=O)[C@@H](NC(=O)C1=NC(=CC=C1)C2=CC=CC=C2)[C@@H](C)O)B(O)O
InChI
InChIKey=SJFBTAPEPRWNKH-CCKFTAQKSA-N
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
| Molecular Formula | C21H28BN3O5 |
| Molecular Weight | 413.275 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 3 / 3 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/22432738Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/18057228
http://adisinsight.springer.com/drugs/800017288
https://newdrugapprovals.org/2015/11/08/cep-18770-delanzomib/
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22432738
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/18057228
http://adisinsight.springer.com/drugs/800017288
https://newdrugapprovals.org/2015/11/08/cep-18770-delanzomib/
Delanzomib (CEP-18770), a proteasome inhibitor, was being developed by Cepahlon (a subsidiary of Teva) for the treatment of cancer and immunological disorders. Delanzomib (CEP-18770) induces apoptotic cell death in multiple myeloma (MM) cell lines and in primary purified CD138-positive explant cultures from untreated and bortezomib-treated MM patients. In vitro, Delanzomib (CEP-18770) has a strong antiangiogenic activity and potently represses RANKL-induced osteoclastogenesis. Delanzomib 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. In vitro studies indicate that this agent exhibits a favorable cytotoxicity profile toward normal human epithelial cells, bone marrow progenitors, and bone marrow-derived stromal cells relative to the proteasome inhibitor bortezomib. Delanzomib has been in phase II clinical trials for the treatment of multiple myeloma (MM). However, this research has been discontinued. Currently Delanzomib is on Phase I clinical trial for Non-Hodgkin's lymphoma and Solid tumours.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL4662 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22978849 |
3.5 nM [IC50] | ||
Target ID: CHEMBL614882 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18057228 |
5.6 nM [IC50] | ||
Target ID: CHEMBL1944494 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18057228 |
10.0 nM [IC50] | ||
Target ID: HS-Sultan anaplastic non-Hodgkin lymphoma Sources: https://www.ncbi.nlm.nih.gov/pubmed/18057228 |
8.2 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
470.7 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23058787 |
1.5 mg/m² 2 times / week multiple, intravenous dose: 1.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DELANZOMIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1454.6 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23058787 |
1.5 mg/m² 2 times / week multiple, intravenous dose: 1.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DELANZOMIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
62 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23058787 |
1.5 mg/m² 2 times / week multiple, intravenous dose: 1.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DELANZOMIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
0.2% |
unknown |
DELANZOMIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Development and validation of a high-performance liquid chromatography-tandem mass spectrometry method for the determination of the novel proteasome inhibitor CEP-18770 in human plasma and its application in a clinical pharmacokinetic study. | 2010-11 |
|
| Discovery of a potent, selective, and orally active proteasome inhibitor for the treatment of cancer. | 2008-02-28 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01023880
Delanzomib (CEP-18770) beginning at a dose of 1.5 mg/m2. Patients will receive I.V. administration on days 1, 8, 15 (up to 8 cycles of 28 days each).
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18057228
TNFa-induced IkappaBalpha degradation was completely blocked by pretreatment with 20nM Delanzomib (CEP-18770)
| Substance Class |
Chemical
Created
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