Page last updated: 2024-12-11

(S)-2-amino-6-boronohexanoic acid

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

(S)-2-amino-6-boronohexanoic acid, also known as **(S)-BHBA**, is a synthetic amino acid analog with a boron-containing side chain. It is a **highly potent and selective inhibitor** of **prolyl hydroxylases (PHDs)**, a family of enzymes that play a crucial role in the regulation of **hypoxia-inducible factor (HIF)** signaling.

Here's why it's important for research:

* **HIF pathway modulation:** HIF is a transcription factor that regulates gene expression in response to low oxygen levels (hypoxia). PHDs normally hydroxylate HIF-α, targeting it for degradation. By inhibiting PHDs, (S)-BHBA stabilizes HIF-α, leading to the activation of HIF-dependent genes, which are involved in various cellular processes, including angiogenesis, erythropoiesis, and glucose metabolism.
* **Drug discovery and development:** (S)-BHBA is a valuable tool for studying the HIF pathway and its role in various diseases. Its selective inhibition of PHDs makes it a promising lead compound for the development of new therapeutic agents targeting **anemia, cancer, and ischemic diseases.**
* **Research tool for cellular biology:** (S)-BHBA can be used to investigate the effects of HIF activation on cellular behavior, including cell proliferation, migration, and survival. It helps researchers understand the underlying mechanisms of HIF signaling and its potential applications in diverse fields.

**Key features of (S)-BHBA:**

* **High potency and selectivity:** It specifically inhibits PHDs with high potency, minimizing off-target effects.
* **Cell permeability:** It readily crosses cell membranes, making it suitable for in vitro and in vivo studies.
* **Metabolic stability:** It exhibits good metabolic stability, ensuring prolonged activity within the body.

**Limitations and considerations:**

* **Toxicity:** While (S)-BHBA has shown promise, its potential toxicities require further investigation.
* **Pharmacokinetic properties:** Optimizing its pharmacokinetic properties (absorption, distribution, metabolism, excretion) is crucial for its therapeutic potential.

Overall, (S)-2-amino-6-boronohexanoic acid is a powerful research tool and a promising candidate for drug development targeting the HIF pathway. Further research is ongoing to explore its full therapeutic potential and address any potential limitations.

(S)-2-amino-6-boronohexanoic acid : L-Norleucine substituted at C-6 with a borono group. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID9793992
CHEMBL ID1812661
CHEBI ID40520
SCHEMBL ID215523

Synonyms (26)

Synonym
CHEBI:40520 ,
(s)-2-amino-6-boronohexanoic acid
6-(dihydroxyboryl)-l-norleucine
(2s)-2-amino-6-(dihydroxyboryl)hexanoic acid
6-borono-l-norleucine
(2s)-2-amino-6-boronohexanoic acid
ABH ,
2(s)-amino-6-boronohexanoic acid
AKOS006284705
CHEMBL1812661 ,
222638-65-5
l-norleucine, 6-borono-
(2s)-2-amino-6-(dihydroxyboranyl)hexanoic acid
gtpl5107
SCHEMBL215523
bdbm130378
2(s)-amino-6-boronohexanoic acid (abh)
DTXSID20430749
mfcd08056094
(r)-2-amino-6-boronohexanoic acid
Q27071909
(s)-abh
4X6P7ZQE7D ,
(s)-2-amino-6-boronohexanoicacid
unii-4x6p7zqe7d
PD020048
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (2)

ClassDescription
organoboron compoundA compound containing at least one carbon-boron bond.
non-proteinogenic L-alpha-amino acidAny L-alpha-amino acid which is not a member of the group of 23 proteinogenic amino acids.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (6)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
ReninHomo sapiens (human)IC50 (µMol)1.47000.00000.77968.2000AID765936
Arginase-1Homo sapiens (human)IC50 (µMol)3.60650.31101.60546.0000AID1540248; AID1548421; AID1649069; AID1695182; AID1780111; AID765936
Arginase-1 Rattus norvegicus (Norway rat)IC50 (µMol)0.80000.80001.20002.0000AID1724055
Arginase-2, mitochondrialHomo sapiens (human)IC50 (µMol)2.15001.92002.03502.1500AID765935
Arginase-2, mitochondrialHomo sapiens (human)Ki0.00850.00850.34381.6000AID1724057; AID612124
ReninMacaca fascicularis (crab-eating macaque)IC50 (µMol)1.47000.06700.76851.4700AID765936
Arginase Plasmodium falciparum 3D7Ki10.000010.000010.000010.0000AID612127
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Arginase-1Homo sapiens (human)Kd0.00930.00500.69873.6000AID1724056; AID612040; AID612126
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (45)

Processvia Protein(s)Taxonomy
kidney developmentReninHomo sapiens (human)
mesonephros developmentReninHomo sapiens (human)
angiotensin maturationReninHomo sapiens (human)
renin-angiotensin regulation of aldosterone productionReninHomo sapiens (human)
proteolysisReninHomo sapiens (human)
regulation of blood pressureReninHomo sapiens (human)
male gonad developmentReninHomo sapiens (human)
hormone-mediated signaling pathwayReninHomo sapiens (human)
response to lipopolysaccharideReninHomo sapiens (human)
response to immobilization stressReninHomo sapiens (human)
drinking behaviorReninHomo sapiens (human)
regulation of MAPK cascadeReninHomo sapiens (human)
cell maturationReninHomo sapiens (human)
amyloid-beta metabolic processReninHomo sapiens (human)
response to cAMPReninHomo sapiens (human)
response to cGMPReninHomo sapiens (human)
cellular response to xenobiotic stimulusReninHomo sapiens (human)
juxtaglomerular apparatus developmentReninHomo sapiens (human)
urea cycleArginase-1Homo sapiens (human)
adaptive immune responseArginase-1Homo sapiens (human)
arginine catabolic processArginase-1Homo sapiens (human)
negative regulation of T cell proliferationArginase-1Homo sapiens (human)
defense response to protozoanArginase-1Homo sapiens (human)
innate immune responseArginase-1Homo sapiens (human)
negative regulation of activated T cell proliferationArginase-1Homo sapiens (human)
negative regulation of type II interferon-mediated signaling pathwayArginase-1Homo sapiens (human)
positive regulation of neutrophil mediated killing of fungusArginase-1Homo sapiens (human)
negative regulation of T-helper 2 cell cytokine productionArginase-1Homo sapiens (human)
arginine catabolic process to ornithineArginase-1Homo sapiens (human)
urea cycleArginase-2, mitochondrialHomo sapiens (human)
ureteric bud developmentArginase-2, mitochondrialHomo sapiens (human)
adaptive immune responseArginase-2, mitochondrialHomo sapiens (human)
negative regulation of type 2 immune responseArginase-2, mitochondrialHomo sapiens (human)
nitric oxide biosynthetic processArginase-2, mitochondrialHomo sapiens (human)
striated muscle contractionArginase-2, mitochondrialHomo sapiens (human)
regulation of interleukin-1 beta productionArginase-2, mitochondrialHomo sapiens (human)
negative regulation of interleukin-13 productionArginase-2, mitochondrialHomo sapiens (human)
negative regulation of interleukin-17 productionArginase-2, mitochondrialHomo sapiens (human)
negative regulation of tumor necrosis factor productionArginase-2, mitochondrialHomo sapiens (human)
innate immune responseArginase-2, mitochondrialHomo sapiens (human)
negative regulation of macrophage inflammatory protein 1 alpha productionArginase-2, mitochondrialHomo sapiens (human)
negative regulation of chemokine (C-C motif) ligand 4 productionArginase-2, mitochondrialHomo sapiens (human)
negative regulation of chemokine (C-C motif) ligand 5 productionArginase-2, mitochondrialHomo sapiens (human)
negative regulation of defense response to bacteriumArginase-2, mitochondrialHomo sapiens (human)
regulation of reactive oxygen species biosynthetic processArginase-2, mitochondrialHomo sapiens (human)
negative regulation of activated CD8-positive, alpha-beta T cell apoptotic processArginase-2, mitochondrialHomo sapiens (human)
negative regulation of CD4-positive, alpha-beta T cell proliferationArginase-2, mitochondrialHomo sapiens (human)
positive regulation of cellular senescenceArginase-2, mitochondrialHomo sapiens (human)
arginine catabolic process to ornithineArginase-2, mitochondrialHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (7)

Processvia Protein(s)Taxonomy
aspartic-type endopeptidase activityReninHomo sapiens (human)
signaling receptor bindingReninHomo sapiens (human)
insulin-like growth factor receptor bindingReninHomo sapiens (human)
protein bindingReninHomo sapiens (human)
peptidase activityReninHomo sapiens (human)
protein bindingArginase-1Homo sapiens (human)
arginase activityArginase-1Homo sapiens (human)
manganese ion bindingArginase-1Homo sapiens (human)
arginase activityArginase-2, mitochondrialHomo sapiens (human)
protein bindingArginase-2, mitochondrialHomo sapiens (human)
manganese ion bindingArginase-2, mitochondrialHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (11)

Processvia Protein(s)Taxonomy
extracellular regionReninHomo sapiens (human)
extracellular spaceReninHomo sapiens (human)
plasma membraneReninHomo sapiens (human)
apical part of cellReninHomo sapiens (human)
extracellular spaceReninHomo sapiens (human)
extracellular regionArginase-1Homo sapiens (human)
extracellular spaceArginase-1Homo sapiens (human)
nucleusArginase-1Homo sapiens (human)
cytosolArginase-1Homo sapiens (human)
azurophil granule lumenArginase-1Homo sapiens (human)
specific granule lumenArginase-1Homo sapiens (human)
cytosolArginase-1Homo sapiens (human)
cytoplasmArginase-1Homo sapiens (human)
mitochondrial matrixArginase-2, mitochondrialHomo sapiens (human)
cytoplasmArginase-2, mitochondrialHomo sapiens (human)
mitochondrionArginase-2, mitochondrialHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (26)

Assay IDTitleYearJournalArticle
AID612126Binding affinity to human arginase 1 using L-arginine as substrate by surface plasmon resonance assay2011Journal of medicinal chemistry, Aug-11, Volume: 54, Issue:15
Binding of α,α-disubstituted amino acids to arginase suggests new avenues for inhibitor design.
AID1724055Inhibition of rat Arg1 at pH 7.42020Bioorganic & medicinal chemistry, 09-15, Volume: 28, Issue:18
Boronic acid-based arginase inhibitors in cancer immunotherapy.
AID612124Binding affinity to human arginase 22011Journal of medicinal chemistry, Aug-11, Volume: 54, Issue:15
Binding of α,α-disubstituted amino acids to arginase suggests new avenues for inhibitor design.
AID1724057Inhibition of human Arg2 at pH 7.52020Bioorganic & medicinal chemistry, 09-15, Volume: 28, Issue:18
Boronic acid-based arginase inhibitors in cancer immunotherapy.
AID1540249Inhibition of human recombinant arginase 2 H331 to I354 deletion mutant expressed in Escherichia coli BL21 (DE3) assessed as reduction in urea production using L-arginine as substrate in presence of MnSO4 incubated for 60 mins by colorimetric assay2019Journal of medicinal chemistry, 09-12, Volume: 62, Issue:17
Discovery of
AID765934Octanol-phosphate buffer partition coefficient, log D of the compound by shake-flask method2013Bioorganic & medicinal chemistry letters, Sep-01, Volume: 23, Issue:17
Synthesis of quaternary α-amino acid-based arginase inhibitors via the Ugi reaction.
AID1649069Inhibition of human arginase1 in presence of DNTB by thio ornithine generation assay2020ACS medicinal chemistry letters, Apr-09, Volume: 11, Issue:4
Discovery and Optimization of Rationally Designed Bicyclic Inhibitors of Human Arginase to Enhance Cancer Immunotherapy.
AID1780111Inhibition of human recombinant ARG1 expressed in Escherichia coli using thioarginine as a substrate preincubated for 30 mins followed by substrate addition and incubated for 60 mins by fluorescence based arginine thio ornithine generating assay2021ACS medicinal chemistry letters, Sep-09, Volume: 12, Issue:9
Structure-Based Discovery of Proline-Derived Arginase Inhibitors with Improved Oral Bioavailability for Immuno-Oncology.
AID739548Antiproliferative activity against HASMC at 1 mM after 96 hrs by MTT assay2013Bioorganic & medicinal chemistry, Mar-01, Volume: 21, Issue:5
Secondary amines containing one aromatic nitro group: preparation, nitrosation, sustained nitric oxide release, and the synergistic effects of released nitric oxide and an arginase inhibitor on vascular smooth muscle cell proliferation.
AID612040Binding affinity to human arginase 12011Journal of medicinal chemistry, Aug-11, Volume: 54, Issue:15
Binding of α,α-disubstituted amino acids to arginase suggests new avenues for inhibitor design.
AID612125Binding affinity to Plasmodium falciparum arginase2011Journal of medicinal chemistry, Aug-11, Volume: 54, Issue:15
Binding of α,α-disubstituted amino acids to arginase suggests new avenues for inhibitor design.
AID739546Induction of nitric oxide release in HASMC at 0.001 to 5 uM after 60 mins by DAF-FM DA assay2013Bioorganic & medicinal chemistry, Mar-01, Volume: 21, Issue:5
Secondary amines containing one aromatic nitro group: preparation, nitrosation, sustained nitric oxide release, and the synergistic effects of released nitric oxide and an arginase inhibitor on vascular smooth muscle cell proliferation.
AID1548421Inhibition of recombinant human arginase 1 using L-arginine as substrate measured after 60 mins in presence of manganese chloride by o-phthaldialdehyde/primaquine diphosphate reagent based colorimetric assay
AID1548440Clearance in Sprague-Dawley rat at 3 mg/kg, iv measured up to 24 hrs by LC-MS/MS analysis
AID1695182Inhibition of recombinant human ARG1 expressed in CHO-K1 cells assessed as reduction in urea level incubated for 24 hrs by colorimetric assay2020RSC medicinal chemistry, May-01, Volume: 11, Issue:5
Synthesis, evaluation and molecular modelling of piceatannol analogues as arginase inhibitors.
AID1540248Inhibition of human recombinant arginase 1 expressed in Escherichia coli BL21 (DE3) assessed as reduction in urea production using L-arginine as substrate in presence of MnSO4 incubated for 60 mins by o-phthaldialdehyde/N-(1-naphthyl)ethylene-diamine dihy2019Journal of medicinal chemistry, 09-12, Volume: 62, Issue:17
Discovery of
AID1540250Selectivity ratio of IC50 for human recombinant arginase 2 H331 to I354 deletion mutant expressed in Escherichia coli BL21 (DE3) to IC50 for human recombinant arginase 1 expressed in Escherichia coli BL21 (DE3)2019Journal of medicinal chemistry, 09-12, Volume: 62, Issue:17
Discovery of
AID765936Inhibition of human arginase-1 assessed as L-arginine conversion to L-ornithine measured as urea level after 1 hr by colorimetric assay2013Bioorganic & medicinal chemistry letters, Sep-01, Volume: 23, Issue:17
Synthesis of quaternary α-amino acid-based arginase inhibitors via the Ugi reaction.
AID765935Inhibition of human arginase-2 assessed as L-arginine conversion to L-ornithine measured as urea level after 1 hr by colorimetric assay2013Bioorganic & medicinal chemistry letters, Sep-01, Volume: 23, Issue:17
Synthesis of quaternary α-amino acid-based arginase inhibitors via the Ugi reaction.
AID1724056Binding affinity to human Arg1 at pH 8.52020Bioorganic & medicinal chemistry, 09-15, Volume: 28, Issue:18
Boronic acid-based arginase inhibitors in cancer immunotherapy.
AID739547Antiproliferative activity against HASMC at 5 mM after 96 hrs by MTT assay2013Bioorganic & medicinal chemistry, Mar-01, Volume: 21, Issue:5
Secondary amines containing one aromatic nitro group: preparation, nitrosation, sustained nitric oxide release, and the synergistic effects of released nitric oxide and an arginase inhibitor on vascular smooth muscle cell proliferation.
AID612127Inhibition of Plasmodium falciparum arginase using L-arginine as substrate by colorimetric assay2011Journal of medicinal chemistry, Aug-11, Volume: 54, Issue:15
Binding of α,α-disubstituted amino acids to arginase suggests new avenues for inhibitor design.
AID1548435Oral bioavailability in Sprague-Dawley rat at 10 mg/kg measured up to 24 hrs by LC-MS/MS analysis
AID1345152Human Arginase II (Arginase)2001Biochemistry, Aug-07, Volume: 40, Issue:31
Classical and slow-binding inhibitors of human type II arginase.
AID1800639ITC from Article 10.1021/bi5004519: \\Crystal Structure of Schistosoma mansoni Arginase, a Potential Drug Target for the Treatment of Schistosomiasis\\2014Biochemistry, Jul-22, Volume: 53, Issue:28
Crystal structure of Schistosoma mansoni arginase, a potential drug target for the treatment of schistosomiasis.
AID1800638Archibald assay from Article 10.1021/bi5004519: \\Crystal Structure of Schistosoma mansoni Arginase, a Potential Drug Target for the Treatment of Schistosomiasis\\2014Biochemistry, Jul-22, Volume: 53, Issue:28
Crystal structure of Schistosoma mansoni arginase, a potential drug target for the treatment of schistosomiasis.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (11)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's1 (9.09)29.6817
2010's5 (45.45)24.3611
2020's5 (45.45)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 22.14

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index22.14 (24.57)
Research Supply Index2.48 (2.92)
Research Growth Index5.55 (4.65)
Search Engine Demand Index15.26 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (22.14)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews1 (9.09%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other10 (90.91%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]