SEMAPIMOD

Details

Stereochemistry	ACHIRAL
Molecular Formula	C34H52N18O2
Molecular Weight	744.8961
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	4
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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=PWDYHMBTPGXCSN-VCBMUGGBSA-N

InChI=1S/C34H52N18O2/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)/b45-19+,46-20+,47-21+,48-22+

HIDE SMILES / InChI

Description
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
toll-like receptor 4 signaling pathway 5 Target ID: GO:0034142 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27194788	Inhibitor 8297		0.3 nM [IC50]
MAP kinase p38 alpha 35 Target ID: CHEMBL260 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9205949	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Crohn's disease 42 Sources: https://clinicaltrials.gov/ct2/show/NCT00741910 http://adisinsight.springer.com/drugs/800007268	Primary		Phase II 1132	Unknown Approved Use Unknown
Autoimmune diseases 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9605164 http://adisinsight.springer.com/drugs/800007268	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

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

T_1/2

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: https://pubmed.ncbi.nlm.nih.gov/11297238 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: https://pubmed.ncbi.nlm.nih.gov/11297238 Page: p.489	Sources: https://pubmed.ncbi.nlm.nih.gov/11297238 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: https://pubmed.ncbi.nlm.nih.gov/20551461 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: https://pubmed.ncbi.nlm.nih.gov/20551461 Page: p,763	Disc. AE: Infusion site reaction... AEs leading to discontinuation/dose reduction: Infusion site reaction (3.9%) Sources: https://pubmed.ncbi.nlm.nih.gov/20551461 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: https://pubmed.ncbi.nlm.nih.gov/11297238 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: https://pubmed.ncbi.nlm.nih.gov/11297238 Page: p.489	Sources: https://pubmed.ncbi.nlm.nih.gov/11297238 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: https://pubmed.ncbi.nlm.nih.gov/20551461 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: https://pubmed.ncbi.nlm.nih.gov/20551461 Page: p,763

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY550530	https://www.001chemical.com/chem/352513-83-8
Achemtek	0102-014020	http://www.achemtek.com/352513-83-8
BLD Pharm	BD01204647	http://www.bldpharm.com/products/352513-83-8.html
BOC Sciences	352513-83-8	https://www.bocsci.com/semapimod-cas-352513-83-8-item-90839.html
DC Chemicals	DC20914	http://www.dcchemicals.com/product_show-DC20914.html
Molcore	MC550530	https://www.molcore.com/product/352513-83-8
OChem	26547	http://www.ocheminc.com/index.php?act=psearch&pid=513S838
Smolecule	S631087	https://www.smolecule.com/products/s631087
THE BioTek	bt-412317	https://www.thebiotek.com/product/others/bt-412317
eNovation Chemicals	D679817	https://www.enovationchem.com/ProductDetails.asp?ProductID=D679817

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

Semapimod 60 mg IV q 6 - 10 weeks

Route of Administration: Intravenous

In Vitro Use Guide

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.

Name

Type

Language

SEMAPIMOD

Official Name

English

N,N'-BIS(3,5-BIS(1- (CARBAMIMIDOYLHYDRAZONO)ETHYL)PHENYL)DECANEDIAMIDE

Common Name

English

semapimod [INN]

Common Name

English

CPSI-2364 FREE BASE

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C2149