RAPASTINEL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H31N5O6
Molecular Weight	413.4686
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]1(CCCN1C(=O)[C@]2([H])CCCN2C(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(N)=O

InChI

InChIKey=GIBQQARAXHVEGD-BSOLPCOYSA-N

InChI=1S/C18H31N5O6/c1-9(24)13(19)18(29)23-8-4-6-12(23)17(28)22-7-3-5-11(22)16(27)21-14(10(2)25)15(20)26/h9-14,24-25H,3-8,19H2,1-2H3,(H2,20,26)(H,21,27)/t9-,10-,11+,12+,13+,14+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24251380
Curator's Comment: description was created based on several sources, including: http://mentalhealthdaily.com/2014/12/17/new-antidepressant-glyx-13-clinical-trials-partial-nmda-receptor-agonist/ | http://www.allergan.com/news/news/thomson-reuters/allergan-s-rapastinel-receives-fda-breakthrough-th | http://www.2shoesapp.com/event_files/280220120233Sussman%20--%20Novel%20Antidepressants%20in%20Development.pdf

Rapastinel (formerly known as GLYX-13) is an investigational intravenous formulation of a novel NMDA receptor partial agonist, which is being evaluated for adjunctive treatment of Major depressive disorder, and has shown a rapid onset of antidepressant efficacy 1 day after a single dose in a Phase 2 clinical trial of patients with Major depressive disorder who had an inadequate response to one or more antidepressants. No psychotomimetic or hallucinogenic side effects were observed with rapastinel. Few adverse events were reported by 5% or more of subjects and these were rated as mild or moderate. These included headache, somnolence, dizziness, dysgeusia, and fatigue. On January 29, 2016, Allergan (who acquired Naurex in July 2015) announced that rapastinel had received Breakthrough Therapy designation from the U.S. FDA for adjunctive treatment of major depressive disorder.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glutamate [NMDA] receptor 125 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16051282 \| https://www.ncbi.nlm.nih.gov/pubmed/18796308	Partial Agonist 290

Conditions

Condition	Modality	Targets	Highest Phase	Product
Obsessive-compulsive disorder 28 Sources: http://adisinsight.springer.com/trials/700250489	Primary		Phase II 1132	Unknown Approved Use Unknown
Major depressive disorder 173 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25782764	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
100 μg/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/24251380/	10 mg/kg single, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	RAPASTINEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
26 μg/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/24251380/	5 mg/kg single, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	RAPASTINEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5.2 μg/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/24251380/	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	RAPASTINEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
182 μg/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/24251380/	20 mg/kg single, intravenous dose: 20 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	RAPASTINEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1162 μg × min/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/24251380/	10 mg/kg single, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	RAPASTINEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
288 μg × min/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/24251380/	5 mg/kg single, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	RAPASTINEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
32 μg × min/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/24251380/	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	RAPASTINEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4030 μg × min/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/24251380/	20 mg/kg single, intravenous dose: 20 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	RAPASTINEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
9 min REVIEW https://pubmed.ncbi.nlm.nih.gov/24251380/	10 mg/kg single, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	RAPASTINEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
7.4 min REVIEW https://pubmed.ncbi.nlm.nih.gov/24251380/	5 mg/kg single, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	RAPASTINEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.7 min REVIEW https://pubmed.ncbi.nlm.nih.gov/24251380/	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	RAPASTINEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
14 min REVIEW https://pubmed.ncbi.nlm.nih.gov/24251380/	20 mg/kg single, intravenous dose: 20 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	RAPASTINEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34567	https://www.001chemical.com/chem/search?q=DY34567
1PlusChem LLC	1P008U64	https://www.1pchem.com/search?query=1P008U64
1PlusChem LLC	1P01EOSP	https://www.1pchem.com/search?query=1P01EOSP
ApexBio Technology	B5419	https://www.apexbt.com/catalogsearch/result/?q=B5419
AstaTech	40930	http://astatechinc.com/CPSResult.php?CRNO=40930
BLD Pharm	BD629952	http://www.bldpharm.com/search/Search.html?keyword=BD629952
BOC Sciences	117928-94-6	http://www.bocsci.com/description.asp?cas=117928-94-6
Cayman Chemical	21385	http://www.caymanchem.com/app/template/Product.vm/catalog/21385
Chem Scene	CS-0040824	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0040824
ChemShuttle	186157	https://www.chemshuttle.com/catalogsearch/result/?q=186157
Excenen	EX-A794	http://www.excenen.com/searchresultlist.php?id=EX-A794
KeyOrganics	AS-55920	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-55920
MedChem Express	HY-16728B	https://www.medchemexpress.com/search.html?q=HY-16728B&ft=&fa=&fp=
MolPort	MolPort-023-276-794	https://www.molport.com/shop/molecule-link/MolPort-023-276-794
MolPort	MolPort-046-418-300	https://www.molport.com/shop/molecule-link/MolPort-046-418-300
Molcore	MC34567	http://www.molcore.com/CatMC34567.html
Molnova	M10606	https://www.molnova.com/en/serch-list.html?keywords=M10606
MuseChem	I000635	https://www.musechem.com/product/I000635.html
TargetMol	T3407	https://www.targetmol.com/search?keyword=T3407
TargetMol	T5819	https://www.targetmol.com/search?keyword=T5819
Tocris	3406	https://www.tocris.com/search.php?Type=QuickSearch&Value=3406
Toronto Research Chemicals	G650020	https://www.trc-canada.com/product-detail/?CatNum=G650020
Toronto Research Chemicals	W498703	https://www.trc-canada.com/product-detail/?CatNum=W498703
eMolecules	32279153	https://orderbb.emolecules.com/search/#?query=32279153
eMolecules	36772578	https://orderbb.emolecules.com/search/#?query=36772578
eMolecules	84106210	https://orderbb.emolecules.com/search/#?query=84106210
mcule	MCULE-7241856385	https://mcule.com/MCULE-7241856385/
mcule	MCULE-8257378228	https://mcule.com/MCULE-8257378228/

PubMed

Title	Date	PubMed
GLYX-13: a monoclonal antibody-derived peptide that acts as an N-methyl-D-aspartate receptor modulator.	2005 Dec	16051282
Antinociceptive action of GLYX-13: an N-methyl-D-aspartate receptor glycine site partial agonist.	2008 Jul 2	18580579
Rapastinel (GLYX-13) has therapeutic potential for the treatment of post-traumatic stress disorder: Characterization of a NMDA receptor-mediated metaplasticity process in the medial prefrontal cortex of rats.	2015 Nov 1	26210936

Patents

Sample Use Guides

In Vivo Use Guide

450 mg weekly injections

Route of Administration: Intravenous

In Vitro Use Guide

The enhancement of burst-evoked NMDAR EPSCs produced by 100 nM–1 uM GLYX-13 and, was converted by ifenprodil into a reduction in NMDAR currents, supporting the hypothesis that GLYX-13 produces enhancement of NMDAR-mediated conductance by a selective action on the glycine site of extrasynaptically enriched NMDARs that contain NR2B subunits.

Name

Type

Language

RAPASTINEL

Official Name

English

RAPASTINELUM

Common Name

English

L-THREONINAMIDE, L-THREONYL-L-PROLYL-L-PROLYL-

Systematic Name

English

TPPT-AMIDE

Common Name

English

L-THREONYL-L-PROLYL-L-PROLYL-L-THREONINAMIDE

Systematic Name

English

GLYX-13

Code

English

rapastinel [INN]

Common Name

English

Rapastinel [WHO-DD]

Common Name

English

RAPASTINEL [USAN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

199404