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 Source | ID |
|---|---|
| PubMed CID | 9793992 |
| CHEMBL ID | 1812661 |
| CHEBI ID | 40520 |
| SCHEMBL ID | 215523 |
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)
| Class | Description |
|---|---|
| organoboron compound | A compound containing at least one carbon-boron bond. |
| non-proteinogenic L-alpha-amino acid | Any 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
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Renin | Homo sapiens (human) | IC50 (µMol) | 1.4700 | 0.0000 | 0.7796 | 8.2000 | AID765936 |
| Arginase-1 | Homo sapiens (human) | IC50 (µMol) | 3.6065 | 0.3110 | 1.6054 | 6.0000 | AID1540248; AID1548421; AID1649069; AID1695182; AID1780111; AID765936 |
| Arginase-1 | Rattus norvegicus (Norway rat) | IC50 (µMol) | 0.8000 | 0.8000 | 1.2000 | 2.0000 | AID1724055 |
| Arginase-2, mitochondrial | Homo sapiens (human) | IC50 (µMol) | 2.1500 | 1.9200 | 2.0350 | 2.1500 | AID765935 |
| Arginase-2, mitochondrial | Homo sapiens (human) | Ki | 0.0085 | 0.0085 | 0.3438 | 1.6000 | AID1724057; AID612124 |
| Renin | Macaca fascicularis (crab-eating macaque) | IC50 (µMol) | 1.4700 | 0.0670 | 0.7685 | 1.4700 | AID765936 |
| Arginase | Plasmodium falciparum 3D7 | Ki | 10.0000 | 10.0000 | 10.0000 | 10.0000 | AID612127 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
Activation Measurements
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Arginase-1 | Homo sapiens (human) | Kd | 0.0093 | 0.0050 | 0.6987 | 3.6000 | AID1724056; AID612040; AID612126 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
Biological Processes (45)
Molecular Functions (7)
| Process | via Protein(s) | Taxonomy |
|---|---|---|
| aspartic-type endopeptidase activity | Renin | Homo sapiens (human) |
| signaling receptor binding | Renin | Homo sapiens (human) |
| insulin-like growth factor receptor binding | Renin | Homo sapiens (human) |
| protein binding | Renin | Homo sapiens (human) |
| peptidase activity | Renin | Homo sapiens (human) |
| protein binding | Arginase-1 | Homo sapiens (human) |
| arginase activity | Arginase-1 | Homo sapiens (human) |
| manganese ion binding | Arginase-1 | Homo sapiens (human) |
| arginase activity | Arginase-2, mitochondrial | Homo sapiens (human) |
| protein binding | Arginase-2, mitochondrial | Homo sapiens (human) |
| manganese ion binding | Arginase-2, mitochondrial | Homo sapiens (human) |
| [Information is prepared from geneontology information from the June-17-2024 release] | ||
Ceullar Components (11)
| Process | via Protein(s) | Taxonomy |
|---|---|---|
| extracellular region | Renin | Homo sapiens (human) |
| extracellular space | Renin | Homo sapiens (human) |
| plasma membrane | Renin | Homo sapiens (human) |
| apical part of cell | Renin | Homo sapiens (human) |
| extracellular space | Renin | Homo sapiens (human) |
| extracellular region | Arginase-1 | Homo sapiens (human) |
| extracellular space | Arginase-1 | Homo sapiens (human) |
| nucleus | Arginase-1 | Homo sapiens (human) |
| cytosol | Arginase-1 | Homo sapiens (human) |
| azurophil granule lumen | Arginase-1 | Homo sapiens (human) |
| specific granule lumen | Arginase-1 | Homo sapiens (human) |
| cytosol | Arginase-1 | Homo sapiens (human) |
| cytoplasm | Arginase-1 | Homo sapiens (human) |
| mitochondrial matrix | Arginase-2, mitochondrial | Homo sapiens (human) |
| cytoplasm | Arginase-2, mitochondrial | Homo sapiens (human) |
| mitochondrion | Arginase-2, mitochondrial | Homo sapiens (human) |
| [Information is prepared from geneontology information from the June-17-2024 release] | ||
Bioassays (26)
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID612126 | Binding affinity to human arginase 1 using L-arginine as substrate by surface plasmon resonance assay | 2011 | Journal of medicinal chemistry, Aug-11, Volume: 54, Issue:15 | Binding of α,α-disubstituted amino acids to arginase suggests new avenues for inhibitor design. |
| AID1724055 | Inhibition of rat Arg1 at pH 7.4 | 2020 | Bioorganic & medicinal chemistry, 09-15, Volume: 28, Issue:18 | Boronic acid-based arginase inhibitors in cancer immunotherapy. |
| AID612124 | Binding affinity to human arginase 2 | 2011 | Journal of medicinal chemistry, Aug-11, Volume: 54, Issue:15 | Binding of α,α-disubstituted amino acids to arginase suggests new avenues for inhibitor design. |
| AID1724057 | Inhibition of human Arg2 at pH 7.5 | 2020 | Bioorganic & medicinal chemistry, 09-15, Volume: 28, Issue:18 | Boronic acid-based arginase inhibitors in cancer immunotherapy. |
| AID1540249 | Inhibition 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 assay | 2019 | Journal of medicinal chemistry, 09-12, Volume: 62, Issue:17 | Discovery of |
| AID765934 | Octanol-phosphate buffer partition coefficient, log D of the compound by shake-flask method | 2013 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 23, Issue:17 | Synthesis of quaternary α-amino acid-based arginase inhibitors via the Ugi reaction. |
| AID1649069 | Inhibition of human arginase1 in presence of DNTB by thio ornithine generation assay | 2020 | ACS medicinal chemistry letters, Apr-09, Volume: 11, Issue:4 | Discovery and Optimization of Rationally Designed Bicyclic Inhibitors of Human Arginase to Enhance Cancer Immunotherapy. |
| AID1780111 | Inhibition 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 assay | 2021 | ACS medicinal chemistry letters, Sep-09, Volume: 12, Issue:9 | Structure-Based Discovery of Proline-Derived Arginase Inhibitors with Improved Oral Bioavailability for Immuno-Oncology. |
| AID739548 | Antiproliferative activity against HASMC at 1 mM after 96 hrs by MTT assay | 2013 | Bioorganic & 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. |
| AID612040 | Binding affinity to human arginase 1 | 2011 | Journal of medicinal chemistry, Aug-11, Volume: 54, Issue:15 | Binding of α,α-disubstituted amino acids to arginase suggests new avenues for inhibitor design. |
| AID612125 | Binding affinity to Plasmodium falciparum arginase | 2011 | Journal of medicinal chemistry, Aug-11, Volume: 54, Issue:15 | Binding of α,α-disubstituted amino acids to arginase suggests new avenues for inhibitor design. |
| AID739546 | Induction of nitric oxide release in HASMC at 0.001 to 5 uM after 60 mins by DAF-FM DA assay | 2013 | Bioorganic & 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. |
| AID1548421 | Inhibition 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 | |||
| AID1548440 | Clearance in Sprague-Dawley rat at 3 mg/kg, iv measured up to 24 hrs by LC-MS/MS analysis | |||
| AID1695182 | Inhibition of recombinant human ARG1 expressed in CHO-K1 cells assessed as reduction in urea level incubated for 24 hrs by colorimetric assay | 2020 | RSC medicinal chemistry, May-01, Volume: 11, Issue:5 | Synthesis, evaluation and molecular modelling of piceatannol analogues as arginase inhibitors. |
| AID1540248 | Inhibition 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 dihy | 2019 | Journal of medicinal chemistry, 09-12, Volume: 62, Issue:17 | Discovery of |
| AID1540250 | Selectivity 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) | 2019 | Journal of medicinal chemistry, 09-12, Volume: 62, Issue:17 | Discovery of |
| AID765936 | Inhibition of human arginase-1 assessed as L-arginine conversion to L-ornithine measured as urea level after 1 hr by colorimetric assay | 2013 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 23, Issue:17 | Synthesis of quaternary α-amino acid-based arginase inhibitors via the Ugi reaction. |
| AID765935 | Inhibition of human arginase-2 assessed as L-arginine conversion to L-ornithine measured as urea level after 1 hr by colorimetric assay | 2013 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 23, Issue:17 | Synthesis of quaternary α-amino acid-based arginase inhibitors via the Ugi reaction. |
| AID1724056 | Binding affinity to human Arg1 at pH 8.5 | 2020 | Bioorganic & medicinal chemistry, 09-15, Volume: 28, Issue:18 | Boronic acid-based arginase inhibitors in cancer immunotherapy. |
| AID739547 | Antiproliferative activity against HASMC at 5 mM after 96 hrs by MTT assay | 2013 | Bioorganic & 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. |
| AID612127 | Inhibition of Plasmodium falciparum arginase using L-arginine as substrate by colorimetric assay | 2011 | Journal of medicinal chemistry, Aug-11, Volume: 54, Issue:15 | Binding of α,α-disubstituted amino acids to arginase suggests new avenues for inhibitor design. |
| AID1548435 | Oral bioavailability in Sprague-Dawley rat at 10 mg/kg measured up to 24 hrs by LC-MS/MS analysis | |||
| AID1345152 | Human Arginase II (Arginase) | 2001 | Biochemistry, Aug-07, Volume: 40, Issue:31 | Classical and slow-binding inhibitors of human type II arginase. |
| AID1800639 | ITC from Article 10.1021/bi5004519: \\Crystal Structure of Schistosoma mansoni Arginase, a Potential Drug Target for the Treatment of Schistosomiasis\\ | 2014 | Biochemistry, Jul-22, Volume: 53, Issue:28 | Crystal structure of Schistosoma mansoni arginase, a potential drug target for the treatment of schistosomiasis. |
| AID1800638 | Archibald assay from Article 10.1021/bi5004519: \\Crystal Structure of Schistosoma mansoni Arginase, a Potential Drug Target for the Treatment of Schistosomiasis\\ | 2014 | Biochemistry, 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)
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 1 (9.09) | 29.6817 |
| 2010's | 5 (45.45) | 24.3611 |
| 2020's | 5 (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.
| This Compound (22.14) All Compounds (24.57) |
Study Types
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 0 (0.00%) | 5.53% |
| Reviews | 1 (9.09%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 10 (90.91%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||