BICIFADINE

Investigational

Details

Stereochemistry	RACEMIC
Molecular Formula	C12H15N
Molecular Weight	173.2542
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC=C(C=C1)[C@@]23C[C@@H]2CNC3

InChI

InChIKey=OFYVIGTWSQPCLF-NEPJUHHUSA-N

InChI=1S/C12H15N/c1-9-2-4-10(5-3-9)12-6-11(12)7-13-8-12/h2-5,11,13H,6-8H2,1H3/t11-,12+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17325229/ | https://www.fiercebiotech.com/biotech/tiny-xtl-cuts-costs-jobs |

Bicifadine (DOV-220075) is not a narcotic and is well-tolerated and, in preclinical studies, has been shown not to act at any opiate receptor, but inhibits monoamine neurotransmitter uptake by recombinant human transporters in vitro with a relative potency of norepinephrine:serotonin:dopamine of 1:2:17. Bicifadine was in Phase II clinical trial for pain caused by diabetic neuropathy, in addition, was in phase III clinical trial to treat Chronic Low Back Pain, but that studies were discontinued

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Sodium-dependent noradrenaline transporter 39 Target ID: P23975 Gene ID: 6530.0 Gene Symbol: SLC6A2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/20046357	Inhibitor 8504	5.0 µM [Ki]
Sodium-dependent serotonin transporter 41 Target ID: P31645 Gene ID: 6532.0 Gene Symbol: SLC6A4 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/20046357	Inhibitor 8504	2.4 µM [Ki]
Sodium-dependent dopamine transporter 43 Target ID: Q01959 Gene ID: 6531.0 Gene Symbol: SLC6A3 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/20046357	Inhibitor 8504	5.2 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic low back pain 3 Sources: https://clinicaltrials.gov/ct2/show/NCT00295724	Primary		Phase III 665	Unknown Approved Use Unknown
Diabetic peripheral neuropathy 8 Sources: https://clinicaltrials.gov/ct2/show/NCT00597649	Palliative		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1780 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17991768/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		BICIFADINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
34271 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17991768/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		BICIFADINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.63 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17991768/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		BICIFADINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
2.2% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17991767/			BICIFADINE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
200 mg single, oral Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/17991768	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/17991768	Sources: https://pubmed.ncbi.nlm.nih.gov/17991768

Sourcing

Vendor/Aggregator	ID	URL
Alfa Chemistry	206567	http://www.alfa-chemistry.com/search.aspx?q=206567
Alfa Chemistry	27372	http://www.alfa-chemistry.com/search.aspx?q=27372
Alfa Chemistry	ACM1014696753	http://www.alfa-chemistry.com/search.aspx?q=ACM1014696753
Alfa Chemistry	ACM66504754	http://www.alfa-chemistry.com/search.aspx?q=ACM66504754
Alfa Chemistry	ACM66504889	http://www.alfa-chemistry.com/search.aspx?q=ACM66504889
BLD Pharm	BD116655	http://www.bldpharm.com/search/Search.html?keyword=BD116655
BOC Sciences	66504-75-4	http://www.bocsci.com/description.asp?cas=66504-75-4
BOC Sciences	66504-82-3	http://www.bocsci.com/description.asp?cas=66504-82-3
Capot Chemical	18323	https://www.capotchem.com/search.do?q=18323
Chemspace	CSC000076809	https://chem-space.com/CSC000076809
Chemspace	CSC015641948	https://chem-space.com/CSC015641948
eMolecules	106969924	https://orderbb.emolecules.com/search/#?query=106969924
eMolecules	28294643	https://orderbb.emolecules.com/search/#?query=28294643
eMolecules	29935521	https://orderbb.emolecules.com/search/#?query=29935521
eMolecules	300448570	https://orderbb.emolecules.com/search/#?query=300448570
Enamine	BBV-38278533	http://www.enaminestore.com/catalog/BBV-38278533
Enamine	BBV-77697769	http://www.enaminestore.com/catalog/BBV-77697769
Enamine	EN300-3004809	https://www.enaminestore.com/catalog/EN300-3004809
Enamine	EN300-6480966	https://www.enaminestore.com/catalog/EN300-6480966
Fragmenta	AZA001	http://www.fragmenta.com/products.asp?SearchOption=0&SEARCHTEXT=AZA001
Lab Network	LN00334345	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00334345
mcule	MCULE-2102946676	https://mcule.com/MCULE-2102946676/
mcule	MCULE-5653532287	https://mcule.com/MCULE-5653532287/
mcule	MCULE-7946328266	https://mcule.com/MCULE-7946328266/
MolPort	MolPort-006-392-874	https://www.molport.com/shop/molecule-link/MolPort-006-392-874
MuseChem	R012271	https://www.musechem.com/product/R012271.html
Princeton BioMolecular Research	PBMR222000	http://www.princetonbio.com/order_online?common_id=PBMR222000
Tocris	4357	https://www.tocris.com/search.php?Type=QuickSearch&Value=4357
Toronto Research Chemicals	B382240	https://www.trc-canada.com/product-detail/?CatNum=B382240

PubMed

Title	Date	PubMed
In vitro metabolism of the analgesic bicifadine in the mouse, rat, monkey, and human.	2007-12	17881661
Characterization of the antinociceptive actions of bicifadine in models of acute, persistent, and chronic pain.	2007-06	17325229

Patents

Sample Use Guides

In Vivo Use Guide

400 mg bid or tid for one year

Route of Administration: Oral

In Vitro Use Guide

Bicifadine interactions with neurotransmitter transporters, receptors, and ion channels were tested, using the radioligand-receptor binding screen. Bicifadine inhibited [125I]RTI-55 binding to sites on recombinant human 5-HT, NE, and DA transporters with moderate (micromolar) but equivalent affinities (1:2:2, respectively). Subsequent functional tests indicated that bicifadine potently inhibited the uptake of [3H]NE and [3H]5-HT by cell lines expressing recombinant human monoamine transporters (IC50 = 55 and 117 nM, respectively), whereas its potency in blocking [3H]DA uptake was approximately one order of magnitude lower (IC50 = 910 nM) (1:2:17, respectively).

Name

Type

Language

(±)-1-P-TOLYL-3-AZABICYCLO(3.1.0)HEXANE

Preferred Name

English

BICIFADINE

Official Name

English

3-AZABICYCLO(3.1.0)HEXANE, 1-(4-METHYLPHENYL)-, (±)-

Systematic Name

English

bicifadine [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C241