Details
Stereochemistry | ACHIRAL |
Molecular Formula | C34H52N18O2.4ClH |
Molecular Weight | 890.74 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 4 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.Cl.Cl.Cl.C\C(=N/NC(N)=N)C1=CC(=CC(NC(=O)CCCCCCCCC(=O)NC2=CC(=CC(=C2)C(\C)=N\NC(N)=N)C(\C)=N\NC(N)=N)=C1)C(\C)=N\NC(N)=N
InChI
InChIKey=MAHASPGBAIQZLY-RTQZJKMDSA-N
InChI=1S/C34H52N18O2.4ClH/c1-19(45-49-31(35)36)23-13-24(20(2)46-50-32(37)38)16-27(15-23)43-29(53)11-9-7-5-6-8-10-12-30(54)44-28-17-25(21(3)47-51-33(39)40)14-26(18-28)22(4)48-52-34(41)42;;;;/h13-18H,5-12H2,1-4H3,(H,43,53)(H,44,54)(H4,35,36,49)(H4,37,38,50)(H4,39,40,51)(H4,41,42,52);4*1H/b45-19+,46-20+,47-21+,48-22+;;;;
Molecular Formula | C34H52N18O2 |
Molecular Weight | 744.8961 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 4 |
Optical Activity | NONE |
Molecular Formula | ClH |
Molecular Weight | 36.461 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/14758776 | http://adisinsight.springer.com/drugs/800007268Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27194788
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14758776 | http://adisinsight.springer.com/drugs/800007268
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27194788
Semapimod (CNI-1493) is a cytokine inhibitor and synthetic guanylhydrazone mitogen-activated protein kinase blocker, is being developed by Cytokine PharmaSciences as a potential treatment for Crohn's disease and other inflammatory conditions. As of December 2001, a phase I study demonstrating the safety of the compound had been completed and phase II trials for psoriasis and Crohn's disease were ongoing. In April 2003, preclinical and early clinical studies were underway for a variety of indications, including congestive heart failure and pancreatitis. Semapimod inhibits activation of p38 MAPK and NF-κB and induction of cyclooxygenase-2 by TLR ligands, but not by IL-1β or stresses. Semapimod inhibits TLR4 signaling (IC50 ≈0.3 umol) and acts by desensitizing cells to LPS; it fails to block responses to LPS concentrations of ≥5 ug/ml. Semapimod had been in phase II clinical trials by Ferring Pharmaceuticals for the treatment of Crohn's disease. However, this research has been discontinued. Semapimod is in phase I clinical trials for the treatment of autoimmune disorders and inflammation.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23147695 | https://www.ncbi.nlm.nih.gov/pubmed/21593565
Curator's Comment: The neuroprotective effect of Semapimod suggests that CNI-1493 might be a valuable neuroprotective candidate in the future treatment of PD.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: GO:0034142 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27194788 |
0.3 nM [IC50] | ||
Target ID: CHEMBL260 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9205949 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
6.2 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11297238 |
32 mg/m² single, intravenous dose: 32 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SEMAPIMOD plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11297238 |
32 mg/m² 1 times / day multiple, intravenous dose: 32 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
SEMAPIMOD plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
432 μg × min/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11297238 |
32 mg/m² single, intravenous dose: 32 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SEMAPIMOD plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
246 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11297238 |
32 mg/m² 1 times / day multiple, intravenous dose: 32 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
SEMAPIMOD plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.42 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11297238 |
32 mg/m² single, intravenous dose: 32 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SEMAPIMOD plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1.02 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11297238 |
32 mg/m² 1 times / day multiple, intravenous dose: 32 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
SEMAPIMOD plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
16 mg/m2 1 times / day multiple, intravenous MTD Dose: 16 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 16 mg/m2, 1 times / day Co-administed with:: Interleukin-2 Sources: Page: p.489 |
unhealthy, ADOLESCENT n = 7 Health Status: unhealthy Condition: melanoma Age Group: ADOLESCENT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: Page: p.489 |
|
60 mg 1 times / day multiple, intravenous Highest studied dose Dose: 60 mg, 1 times / day Route: intravenous Route: multiple Dose: 60 mg, 1 times / day Sources: Page: p,763 |
unhealthy, ADULT n = 51 Health Status: unhealthy Condition: Crohn's disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 51 Sources: Page: p,763 |
Disc. AE: Infusion site reaction... AEs leading to discontinuation/dose reduction: Infusion site reaction (3.9%) Sources: Page: p,763 |
32 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 32 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 32 mg/m2, 1 times / day Sources: Page: p.489 |
unhealthy, ADULT n = 6 Health Status: unhealthy Condition: melanoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: Page: p.489 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Infusion site reaction | 3.9% Disc. AE |
60 mg 1 times / day multiple, intravenous Highest studied dose Dose: 60 mg, 1 times / day Route: intravenous Route: multiple Dose: 60 mg, 1 times / day Sources: Page: p,763 |
unhealthy, ADULT n = 51 Health Status: unhealthy Condition: Crohn's disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 51 Sources: Page: p,763 |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00741910
Semapimod 60 mg IV q 6 - 10 weeks
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27194788
Semapimod inhibits degradation of IkBa
induced by LPS concentrations up to 1 ug/ml, but is ineffective at 5 ug/ml in IEC-6 cells. Semapimod (2 umol) blocks LPS-induced recruitment of MyD88 to cell surface.
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 18:11:52 GMT 2023
by
admin
on
Fri Dec 15 18:11:52 GMT 2023
|
Record UNII |
A16WYQ522A
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Code | English | ||
|
Common Name | English |
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
100000175159
Created by
admin on Fri Dec 15 18:11:52 GMT 2023 , Edited by admin on Fri Dec 15 18:11:52 GMT 2023
|
PRIMARY | |||
|
9554199
Created by
admin on Fri Dec 15 18:11:52 GMT 2023 , Edited by admin on Fri Dec 15 18:11:52 GMT 2023
|
PRIMARY | |||
|
A16WYQ522A
Created by
admin on Fri Dec 15 18:11:52 GMT 2023 , Edited by admin on Fri Dec 15 18:11:52 GMT 2023
|
PRIMARY | |||
|
DBSALT002134
Created by
admin on Fri Dec 15 18:11:52 GMT 2023 , Edited by admin on Fri Dec 15 18:11:52 GMT 2023
|
PRIMARY | |||
|
NCT00740103
Created by
admin on Fri Dec 15 18:11:52 GMT 2023 , Edited by admin on Fri Dec 15 18:11:52 GMT 2023
|
PRIMARY | Long-term Study of Semapimod (CNI-1493) for Treatment of Crohn's Disease (CD05) | ||
|
164301-51-3
Created by
admin on Fri Dec 15 18:11:52 GMT 2023 , Edited by admin on Fri Dec 15 18:11:52 GMT 2023
|
PRIMARY | |||
|
DTXSID301028119
Created by
admin on Fri Dec 15 18:11:52 GMT 2023 , Edited by admin on Fri Dec 15 18:11:52 GMT 2023
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
SOLVATE->ANHYDROUS | |||
|
PARENT -> SALT/SOLVATE |
Related Record | Type | Details | ||
---|---|---|---|---|
|
ACTIVE MOIETY |