ARIMOCLOMOL CITRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C14H20ClN3O3.C6H8O7
Molecular Weight	505.903
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CC(O)(CC(O)=O)C(O)=O.O[C@@H](CON=C(Cl)C1=C[N+]([O-])=CC=C1)CN2CCCCC2

InChI

InChIKey=XSENLDLUMVYRET-BTQNPOSSSA-N

InChI=1S/C14H20ClN3O3.C6H8O7/c15-14(12-5-4-8-18(20)9-12)16-21-11-13(19)10-17-6-2-1-3-7-17;7-3(8)1-6(13,5(11)12)2-4(9)10/h4-5,8-9,13,19H,1-3,6-7,10-11H2;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/t13-;/m1./s1

HIDE SMILES / InChI

Description
Sources: https://www.drugbank.ca/drugs/DB05025
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27605553 | https://clinicaltrials.gov/ct2/show/NCT00706147 | https://clinicaltrials.gov/ct2/show/NCT00706147 | https://www.ncbi.nlm.nih.gov/pubmed/27273088

Arimoclomol (INN; originally codenamed BRX-345, which is a citrate salt formulation of BRX-220) is an experimental drug developed by a biopharmaceutical company CytRx Corporation. In 2011 the worldwide rights to arimoclomol were bought by Danish biotech company Orphazyme ApS. The European Medicines Agency (EMA) and U.S. Food & Drug Administration (FDA) granted orphan drug designation to arimoclomol as a potential treatment for Niemann-Pick type C in 2014 and 2015 respectively. Arimoclomol is believed to function by stimulating a normal cellular protein repair pathway through the activation of molecular chaperones. Since damaged proteins, called aggregates, are thought to play a role in many diseases, CytRx believes that arimoclomol could treat a broad range of diseases.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Heat shock 70 kDa protein 1 6 Target ID: CHEMBL5460 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27605553	Activator 1430

Conditions

Condition	Modality	Highest Phase	Product
Amyotrophic lateral sclerosis 41 Sources: https://clinicaltrials.gov/ct2/show/NCT00706147	Primary	Phase III 656	Unknown Approved Use Unknown
Inclusion body myositis 3 Sources: https://clinicaltrials.gov/ct2/show/NCT00706147	Primary	Phase III 656	Unknown Approved Use Unknown
Niemann-Pick disease, type C 4 Sources: https://clinicaltrials.gov/ct2/show/NCT02612129	Primary	Phase III 656	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
100 mg 3 times / day multiple, oral Highest studied dose Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18551622/	unhealthy n = 20 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/18551622/	Disc. AE: pulmonary embolism, increased lower extremity weakness... AEs leading to discontinuation/dose reduction: pulmonary embolism (1 pt) increased lower extremity weakness (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/18551622/
25 mg 3 times / day multiple, oral (unknown) Studied dose Dose: 25 mg, 3 times / day Route: oral Route: multiple Dose: 25 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18551622/	unhealthy n = 19 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/18551622/	Disc. AE: rash... AEs leading to discontinuation/dose reduction: rash (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/18551622/

AEs

AE	Significance	Dose	Population
increased lower extremity weakness	1 pt Disc. AE	100 mg 3 times / day multiple, oral Highest studied dose Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18551622/	unhealthy n = 20 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/18551622/
pulmonary embolism	1 pt Disc. AE	100 mg 3 times / day multiple, oral Highest studied dose Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18551622/	unhealthy n = 20 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/18551622/
rash	1 pt Disc. AE	25 mg 3 times / day multiple, oral (unknown) Studied dose Dose: 25 mg, 3 times / day Route: oral Route: multiple Dose: 25 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18551622/	unhealthy n = 19 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/18551622/

PubMed

Title	Date	PubMed
Heat shock protein-based therapy as a potential candidate for treating the sphingolipidoses.	2016 Sep 7	27605553

Patents

Sample Use Guides

In Vivo Use Guide

PO (3 times daily). Doses:150-600 mg/day (based on weight)

Route of Administration: Oral

In Vitro Use Guide

Human SH-SY5Y cells were used for activity evaluation. For quantitative analysis, of cell viability by fluorescence microscopy, cells were harvested at the indicated time point after single or co-application of celastrol and Arimoclomol (50 or 250 mkM). An equal volume of cell suspension was mixed with 0.4 % trypan blue (T10282; Life Technologies) and incubated for 2 min. The cell suspension was loaded into a disposable Countess® cell counting chamber slide, and the percent of cells stained by trypan blue was quantified using a Countess® automated cell counter.

Name

Type

Language

ARIMOCLOMOL CITRATE

Official Name

English

ARIMOCLOMOL CITRATE [USAN]

Common Name

English

3-PYRIDINECARBOXIMIDOYL CHLORIDE, N-((2R)-2-HYDROXY-3-(1-PIPERIDINYL)PROPOXY)-, 1-OXIDE, 2-HYDROXY-1,2,3-PROPANETRICARBOXYLATE (1:1)

Systematic Name

English

ARIMOCLOMOL CITRATE [MI]

Common Name

English

ORPHAZYME A/S

Brand Name

English

N-[(2R)-2-Hydroxy-3-(1-piperidyl)propoxy]pyridine-3-carboximidoyl chloride, 1-oxide, 2-hydroxy-1,2,3-propanetricarboxylate

Systematic Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/16/1659