U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C22H34O2
Molecular Weight 330.5042
Optical Activity UNSPECIFIED
Defined Stereocenters 7 / 7
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PREGNENOLONE METHYL ETHER

SMILES

[H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)CC[C@@]3([H])[C@@]2([H])CC=C4C[C@H](CC[C@]34C)OC

InChI

InChIKey=ZVGQOQHAMHMMNE-BIBIXIOVSA-N
InChI=1S/C22H34O2/c1-14(23)18-7-8-19-17-6-5-15-13-16(24-4)9-11-21(15,2)20(17)10-12-22(18,19)3/h5,16-20H,6-13H2,1-4H3/t16-,17-,18+,19-,20-,21-,22+/m0/s1

HIDE SMILES / InChI

Molecular Formula C22H34O2
Molecular Weight 330.5042
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 7 / 7
E/Z Centers 0
Optical Activity UNSPECIFIED

Mapreg is developing pregnenolone methyl ether (MAP4343), an injectable neurosteroid stimulator of the tubulin polymerisation and neurite growth stimulator. The synthetic pregnenolone-derivative MAP4343 (3β-methoxy-preg-nenolone) binds in vitro to microtubule-associated-protein 2 (MAP2), stimulates the polymerization of tubulin, enhances the extension of neurites and protects neurons against neurotoxic agents. MAP4343 has been selected after screening of a large library ofnatural and synthetic steroids. MAP4343 has similar in vitro activity as pregnenolone; it cannot be converted into metabolites with hormonal activities, and has been shown to have in vivo beneficial effects in rat models of spinal cord injury. MAP4343 has an interesting pharmacological profile because no in vitro affinity for any CNS neurotransmitter receptor was found. MAP4343 has been shown to have antidepressant efficacy in rats. In the rat isolation-rearing model of depression, administration of MAP4343 showed persistent efficacy in recovering recognition memory deficit, stronger and more rapid anxiolytic activity, and more rapid rescue of passive coping behavior compared with FLX. The behavioral effects of MAP4343 correlated with changes in α-tubulin isoforms in the hippocampus, amygdala, and pre-frontal cortex (PFC). Its efficacy was also assessed in vivo with the most commonly used thoracic spinal cord compression/contusion models in rats. In the three models used, the post-traumatic subcutaneous injection of MAP4343 significantly improved the recovery of locomotor function after spinal cord injury, as shown by an earlier and more complete recovery compared to vehicle-treated rats. The results obtained in three different rat models of spinal cord injury demonstrate the beneficial effects of this therapeutic strategy and identify MAP4343 as a potential treatment for acute spinal cord injury. MAP4343 received EU Orphan Drug designation for spinal cord injury. MAP4343 is in phase II clinical trials by Mapreg for the treatment of depression and in phase I clinical trials for the treatment of spinal cord injury and traumatic brain injury.

CNS Activity

Curator's Comment: In mice, a single subcutaneous dose of MAP4343 was able to cross the blood brain barrier, enter the hippocampus and induce changes in isoforms of tubulin-α, the endogenous substrate of MAP2.

Approval Year

PubMed

PubMed

TitleDatePubMed
A study of the action of pregnenolone methyl ether in patients with rheumatoid arthritis.
1954
Experimental use of pregnenolone methyl ether in treating psychiatric symptoms.
1955 Mar
Side-chain cleavage of cholesterol esters by human cytochrome P-450(scc).
1996 Aug
3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders.
2012 Jan 31
Patents

Patents

Sample Use Guides

Spinal cord compression was induced by epidural balloon inflation at thoracic level in rats. MAP4343-treatment (first injection, 5 min after injury, 12 mg/kg/day for 28 days) provided a significant improvement of the BBB score already 12 days after injury. MAP4343-treatment at 12 mg/kg significantly increased the number of animals able to walk with weight-supported plantar steps (BBB score≥10) from 12 to 28 days after injury when compared to vehicle-treated animals. MAP4343 was dissolved in sesame oil and injected under the backskin.
Route of Administration: Other
Substance Class Chemical
Created
by admin
on Sat Dec 16 08:53:38 GMT 2023
Edited
by admin
on Sat Dec 16 08:53:38 GMT 2023
Record UNII
TU767RK7YN
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PREGNENOLONE METHYL ETHER
MI  
Common Name English
PREGNENOLONE METHYL ETHER [MI]
Common Name English
L-542856-0
Code English
3.BETA.-METHOXY-5-PREGNEN-20-ONE
Systematic Name English
3-METHOXY-PREGNENOLONE
Common Name English
PREGNENOLONE 3-METHYL ETHER
Common Name English
3.BETA.-METHOXYPREGNENOLONE
Common Name English
MAP-4343
Code English
NSC-31617
Code English
PREGN-5-EN-20-ONE, 3-METHOXY-, (3.BETA.)-
Systematic Name English
Classification Tree Code System Code
EU-Orphan Drug EU/3/07/511
Created by admin on Sat Dec 16 08:53:38 GMT 2023 , Edited by admin on Sat Dec 16 08:53:38 GMT 2023
Code System Code Type Description
EVMPD
SUB193918
Created by admin on Sat Dec 16 08:53:38 GMT 2023 , Edited by admin on Sat Dec 16 08:53:38 GMT 2023
PRIMARY
CAS
511-26-2
Created by admin on Sat Dec 16 08:53:38 GMT 2023 , Edited by admin on Sat Dec 16 08:53:38 GMT 2023
PRIMARY
PUBCHEM
233254
Created by admin on Sat Dec 16 08:53:38 GMT 2023 , Edited by admin on Sat Dec 16 08:53:38 GMT 2023
PRIMARY
MERCK INDEX
m9121
Created by admin on Sat Dec 16 08:53:38 GMT 2023 , Edited by admin on Sat Dec 16 08:53:38 GMT 2023
PRIMARY Merck Index
SMS_ID
100000178276
Created by admin on Sat Dec 16 08:53:38 GMT 2023 , Edited by admin on Sat Dec 16 08:53:38 GMT 2023
PRIMARY
EPA CompTox
DTXSID901304765
Created by admin on Sat Dec 16 08:53:38 GMT 2023 , Edited by admin on Sat Dec 16 08:53:38 GMT 2023
PRIMARY
WIKIPEDIA
3β-Methoxypregnenolone
Created by admin on Sat Dec 16 08:53:38 GMT 2023 , Edited by admin on Sat Dec 16 08:53:38 GMT 2023
PRIMARY
FDA UNII
TU767RK7YN
Created by admin on Sat Dec 16 08:53:38 GMT 2023 , Edited by admin on Sat Dec 16 08:53:38 GMT 2023
PRIMARY
NSC
31617
Created by admin on Sat Dec 16 08:53:38 GMT 2023 , Edited by admin on Sat Dec 16 08:53:38 GMT 2023
PRIMARY