2-IMINOBIOTIN

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H17N3O2S
Molecular Weight	243.326
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12CS[C@@H](CCCCC(O)=O)[C@@]1([H])NC(=N)N2

InChI

InChIKey=WWVANQJRLPIHNS-ZKWXMUAHSA-N

InChI=1S/C10H17N3O2S/c11-10-12-6-5-16-7(9(6)13-10)3-1-2-4-8(14)15/h6-7,9H,1-5H2,(H,14,15)(H3,11,12,13)/t6-,7-,9-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27524449
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT02836340 | https://www.ncbi.nlm.nih.gov/pubmed/27780726 | https://clinicaltrials.gov/ct2/show/NCT01626924

2-Iminobiotin (2-IB) is a cyclic guanidino analog of biotin (Vitamin B7) and combined neuronal and inducible (but not endothelial) nitric oxide synthase inhibitor that has been demonstrated to improve neuroprotection in animal models of hypoxic-ischemic Brain Injury. While the exact mechanism of action has yet to be defined, 2-Iminobiotin potentially protects against hypoxic-ischemic brain damage by preventing nitric oxide or peroxynitrite-induced mitochondrial damage. In preclinical models, 2-Iminobiotin provides gender-specific neuroprotection against hypoxia-ischemia in neonatal rats by a NO-independent mechanism.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Nitric oxide synthase, inducible 50 Target ID: CHEMBL4481 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7526856	Inhibitor 8297		21.8 nM [Ki]
Nitric-oxide synthase, brain 24 Target ID: CHEMBL3568 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7526856	Inhibitor 8297		37.5 µM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Perinatal asphyxia 1 Sources: https://clinicaltrials.gov/ct2/show/NCT01626924	Primary	Phase II 1132	Unknown Approved Use Unknown
Cardiac arrest 19 Sources: https://clinicaltrials.gov/ct2/show/NCT02836340	Primary	Phase II 1132	Unknown Approved Use Unknown
Hypoxic-ischemic brain injury 3 Sources: https://clinicaltrials.gov/ct2/show/NCT02836340	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
22541 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31625480	6 mg/kg 6 times / day multiple, intravenous dose: 6 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	2-IMINOBIOTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
34175 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31625480	12 mg/kg 6 times / day multiple, intravenous dose: 12 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	2-IMINOBIOTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1808 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31625480	0.6 mg/kg single, intravenous dose: 0.6 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	2-IMINOBIOTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
16448 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31625480	6 mg/kg 6 times / day multiple, intravenous dose: 6 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	2-IMINOBIOTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
39956 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31625480	12 mg/kg 6 times / day multiple, intravenous dose: 12 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	2-IMINOBIOTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1528 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31625480	0.6 mg/kg single, intravenous dose: 0.6 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	2-IMINOBIOTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
2.12 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31625480	6 mg/kg 6 times / day multiple, intravenous dose: 6 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	2-IMINOBIOTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.37 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31625480	12 mg/kg 6 times / day multiple, intravenous dose: 12 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	2-IMINOBIOTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.48 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31625480	0.6 mg/kg single, intravenous dose: 0.6 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	2-IMINOBIOTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
12 mg/kg 6 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 6 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155	Disc. AE: Dizziness, Headache... AEs leading to discontinuation/dose reduction: Dizziness (grade 1-2, 33.3%) Headache (grade 1, 16.7%) Pallor of skin (grade 1, 16.7%) Malaise (grade 2, 16.7%) Abdominal pain (grade 1, 16.7%) Nausea (grade 2, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155
6 mg/kg 6 times / day multiple, intravenous MTD Dose: 6 mg/kg, 6 times / day Route: intravenous Route: multiple Dose: 6 mg/kg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155	Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155

AEs

AE	Significance	Dose	Population
Abdominal pain	grade 1, 16.7% Disc. AE	12 mg/kg 6 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 6 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155
Headache	grade 1, 16.7% Disc. AE	12 mg/kg 6 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 6 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155
Pallor of skin	grade 1, 16.7% Disc. AE	12 mg/kg 6 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 6 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155
Dizziness	grade 1-2, 33.3% Disc. AE	12 mg/kg 6 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 6 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155
Malaise	grade 2, 16.7% Disc. AE	12 mg/kg 6 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 6 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155
Nausea	grade 2, 33.3% Disc. AE	12 mg/kg 6 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 6 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/31625480 Page: p.155

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P007N3U	https://www.1pchem.com/search?query=1P007N3U
Achemo Scientific Limited	AC-106791	http://www.achemo.com/search/?Keyword=AC-106791
BLD Pharm	BD763967	http://www.bldpharm.com/search/Search.html?keyword=BD763967
BOC Sciences	13395-35-2	http://www.bocsci.com/description.asp?cas=13395-35-2
BioSynth	W-201113	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/W-201113
Cayman Chemical	20812	http://www.caymanchem.com/app/template/Product.vm/catalog/20812
Chem Scene	CS-0068276	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0068276
Chem Scene	CS-0115752	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0115752
Chemspace	CSC029883415	https://chem-space.com/CSC029883415
Chemspace	CSC042875755	https://chem-space.com/CSC042875755
Chemspace	CSC045780451	https://chem-space.com/CSC045780451
Combi-Blocks	QJ-7769	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-7769
Enamine	BBV-78304254	http://www.enaminestore.com/catalog/BBV-78304254
Enamine	BBV-78352540	http://www.enaminestore.com/catalog/BBV-78352540
Enamine	BBV-78564656	http://www.enaminestore.com/catalog/BBV-78564656
KeyOrganics	AS-74208	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-74208
Lab Network	LN01304908	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01304908
MedChem Express	HY-118700	https://www.medchemexpress.com/search.html?q=HY-118700&ft=&fa=&fp=
MedChem Express	HY-118700A	https://www.medchemexpress.com/search.html?q=HY-118700A&ft=&fa=&fp=
MolPort	MolPort-003-936-924	https://www.molport.com/shop/molecule-link/MolPort-003-936-924
MolPort	MolPort-004-964-670	https://www.molport.com/shop/molecule-link/MolPort-004-964-670
MolPort	MolPort-019-879-309	https://www.molport.com/shop/molecule-link/MolPort-019-879-309
Synthonix	T18763	https://synthonix.com/catalogsearch/result/?q=T18763
TargetMol	T7206	https://www.targetmol.com/search?keyword=T7206
Wonderchem	WD053RS	http://www.wonder-chem.com/search.html?text=WD053RS
eMolecules	194926250	https://orderbb.emolecules.com/search/#?query=194926250
eMolecules	26750750	https://orderbb.emolecules.com/search/#?query=26750750
eMolecules	49225788	https://orderbb.emolecules.com/search/#?query=49225788
eMolecules	49240304	https://orderbb.emolecules.com/search/#?query=49240304
mcule	MCULE-4180770968	https://mcule.com/MCULE-4180770968/

PubMed

Title	Date	PubMed
Short-term dose-response characteristics of 2-iminobiotin immediately postinsult in the neonatal piglet after hypoxia-ischemia.	2013 Mar	23362078

Patents

Sample Use Guides

In Vivo Use Guide

2-Iminobiotin is formulated as a 0.75 mg/ml isotonic, iso-osmotic, saline solution with a pH of 4. It is administered as a solution for I.V.infusion through a central catheter. Six pulse doses will be given in 20 hours. Dosage will starts with 0.2 mg/kg/dose, but may be adapted during the study.

Route of Administration: Intravenous

In Vitro Use Guide

Neuronal IMR-32 cells were exposed to hypoxia employing an enzymatic hypoxia system and were thereafter incubated with various concentrations of 2-IB (10 to 300ng/ml). Cell damage, metabolic activity and generation of reactive oxygen species were quantified using colorimetric/fluorometric lactate dehydrogenase (LDH), tetrazolium-based (MTS) and reactive oxygen species assays. Proteome profiling arrays were performed to evaluate the regulation of cell stress protein expression by hypoxia and 2-IB. Seven hours of hypoxia led to morphological changes in IMR-32 cultures, increased neuronal cell damage, reduction of metabolic activity and enhanced reactive oxygen species production. Post-hypoxic application of 2-IB (30ng/ml) attenuated hypoxia-induced LDH release and increased metabolic activity of IMR-32 cells, while reactive oxygen species production was only by trend decreased.

Name

Type

Language

2-IMINOBIOTIN

Common Name

English

1H-THIENO(3,4-D)IMIDAZOLE-4-PENTANOIC ACID, 2-AMINO-3A,4,6,6A-TETRAHYDRO-, (3AS,4S,6AR)-

Common Name

English

HEXAHYDRO-2-IMINO-1H-THIENO(3,4-D)IMIDAZOLE-4-PENTANOIC ACID

Systematic Name

English

1H-THIENO(3,4-D)IMIDAZOLE-6-PENTANOIC ACID, 2-AMINO-3A,4,6,6A-TETRAHYDRO-, (3AR,6S,6AS)-

Common Name

English

THIENO(3,4-D)IMIDAZOLINE-4-VALERIC ACID, TETRAHYDRO-2-IMINO-

Common Name

English

5-((3AS,4S,6AR)-2-IMINOHEXAHYDRO-1H-THIENO(3,4-D)IMIDAZOL-4-YL)PENTANOIC ACID

Common Name

English

GUANIDINOBIOTIN

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

275609