OLESOXIME, E-

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H45NO
Molecular Weight	399.6523
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CCC4=C\C(CC[C@]4(C)[C@H]3CC[C@]12C)=N\O

InChI

InChIKey=QNTASHOAVRSLMD-SIWSWZRQSA-N

InChI=1S/C27H45NO/c1-18(2)7-6-8-19(3)23-11-12-24-22-10-9-20-17-21(28-29)13-15-26(20,4)25(22)14-16-27(23,24)5/h17-19,22-25,29H,6-16H2,1-5H3/b28-21+/t19-,22+,23-,24+,25+,26+,27-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C27H45NO
Molecular Weight	399.6523
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	7 / 7
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28460889 | https://www.roche.com/media/store/releases/med-cor-2015-01-16.htm | https://clinicaltrials.gov/ct2/show/NCT01808885

Olesoxime (TRO19622) a small-molecule with a cholesterol-like structure has remarkable neuroprotective properties for motor neurons in cell culture and in rodents. The biopharmaceutical company Trophos initially developed this compound. This medicine is in phase II clinical trial in treating spinal muscular atrophy and in phase I for patients with stable relapsing remitting multiple sclerosis. This drug was also investigated in phase III clinical trial for amyotrophic lateral sclerosis, but it did not demonstrate a significant increase in survival versus placebo and that study was discontinued. Preclinical studies have demonstrated that the olesoxime promoted the function and survival of neurons and other cell types under disease-relevant stress conditions through interactions with the mitochondrial permeability transition pore (mPTP).

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
mitochondrial permeability transition pore 1 Target ID: mitochondrial permeability transition pore Sources: https://www.ncbi.nlm.nih.gov/pubmed/20721828	Modulator 846

Conditions

Condition	Modality	Highest Phase	Product
Spinal muscular atrophy 4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28460889	Primary	Phase II 1147	Unknown Approved Use Unknown
Relapsing-remitting multiple sclerosis 8 Sources: https://clinicaltrials.gov/ct2/show/NCT01808885	Primary	Phase I 438	Unknown Approved Use Unknown
Amyotrophic lateral sclerosis 39 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24447620	Primary	Phase III 665	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2A6 879 CYP2E1 1060 CYP2C19 2057 CYP19A1 429	UGT1A6 343 P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/996#section=Biological-Test-Results Page: 42.0	no [IC50 43.2771 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE0MDYwIn19	no [IC50 >10 uM]
CYP2A6 911	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE0MDYwIn19	no [IC50 >10 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE0MDYwIn19	no [IC50 >10 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE0MDYwIn19	no [IC50 >10 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTQwNjAifX0=	no [IC50 >10 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE0MDYwIn19	no [IC50 >10 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTQwNjAifX0=	no [IC50 >10 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/996#section=Biological-Test-Results Page: 373 \| 375	no
UGT1A6 343	substrate 4014 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMzE2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE0MDYwIn19	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTQwNjAifX0=

PubMed

Title	Date	PubMed
Olesoxime prevents microtubule-targeting drug neurotoxicity: selective preservation of EB comets in differentiated neuronal cells.	2010-09-15	20417191
Olesoxime, a cholesterol-like neuroprotectant for the potential treatment of amyotrophic lateral sclerosis.	2010-08	20721828
Clinical trials in CNS--SMi's eighth annual conference.	2010-02	20127552
Olesoxime (cholest-4-en-3-one, oxime): analgesic and neuroprotective effects in a rat model of painful peripheral neuropathy produced by the chemotherapeutic agent, paclitaxel.	2009-12-15	19833436
Mitochondrial calcium and the permeability transition in cell death.	2009-11	19576166
Dysfunction of mitochondria and sarcoplasmic reticulum in the pathogenesis of collagen VI muscular dystrophies.	2008-12	19076452
Specific antinociceptive activity of cholest-4-en-3-one, oxime (TRO19622) in experimental models of painful diabetic and chemotherapy-induced neuropathy.	2008-08	18492948
Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis.	2007-08	17496168

Sample Use Guides

In Vivo Use Guide

Participants will receive 10 milligrams per kilogram (mg/kg) suspension once a day either orally or via a naso-gastric or gastrostomy tube with the main meal (preferably at the same time of the day)

Route of Administration: Oral

In Vitro Use Guide

Neuroprotective dose-effect of olesoxime against motor neuron cell death was studied. Rat embryonic motor neurons were cultured in 96-well plates in the absence of trophic factors and with increasing concentrations of olesoxime (concentrations ranging from 0.1 to 10 µM), or with pure syn or anti forms of olesoxime. Motor neuron survival was measured after 3 days or 7 days in vitro by direct counting of live cells labeled with calcein-AM. Survival is expressed as a ratio of surviving cell (A-B) relative to positive controls treated with a cocktail of neurotrophic factors (NTFs) and negative controls that received DMSO alone (0.1%). Treatment with olesoxime produced a dose-dependent increase in cell survival with EC50 around 3 µM. Importantly, both syn and anti forms were equally potent.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 22:19:55 GMT 2025` Edited by `admin` on `Mon Mar 31 22:19:55 GMT 2025`
Record UNII	8V8EF6094N
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

OLESOXIME, E-

Preferred Name

English

Code System Code Type Description

PUBCHEM

9930827

Created by admin on Mon Mar 31 22:19:55 GMT 2025 , Edited by admin on Mon Mar 31 22:19:55 GMT 2025

PRIMARY

CAS

66538-08-7

Created by admin on Mon Mar 31 22:19:55 GMT 2025 , Edited by admin on Mon Mar 31 22:19:55 GMT 2025

PRIMARY

FDA UNII

8V8EF6094N

Created by admin on Mon Mar 31 22:19:55 GMT 2025 , Edited by admin on Mon Mar 31 22:19:55 GMT 2025

PRIMARY

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/28460889 | https://www.roche.com/media/store/releases/med-cor-2015-01-16.htm | https://clinicaltrials.gov/ct2/show/NCT01808885

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Approved Use

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28460889 | https://www.roche.com/media/store/releases/med-cor-2015-01-16.htm | https://clinicaltrials.gov/ct2/show/NCT01808885

Drug as perpetrator