| Size | Price | Stock | Qty |
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| 250mg |
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| Targets |
Incubating tumor cells with 10 mM L-2,4-diaminobutyric acid for 24 hours at 37°C causes irreversible and total destruction. L-DABA's cell-damaging actions could be attributed to osmotic lysis caused by non-saturated intracellular buildup of the compound. L-DABA's deleterious effects can be removed by incubating it with L-alanine and L-methionine at the same time [1]. Kinetic investigations show that L-DABA is a non-linear, non-competitive inhibitor of GABA transaminase activity. The rise in GABA levels induced by L-DABA is consistent with the suppression of GABA transaminase activity [2]. L-2,4-diaminobutyric acid is an amino acid analog that has cytotoxic effects on the human glioma cell line SKMG-1 and normal human fibroblasts. The L-DABA concentration needed to reduce cell counts to 50% of control after 24 hours of incubation at 37°C is 12.5 mM for human fibroblasts and 20 mM for glioma cell lines [3].
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| ln Vitro |
Incubating tumor cells with 10 mM L-2,4-diaminobutyric acid for 24 hours at 37°C causes irreversible and total destruction. L-DABA's cell-damaging actions could be attributed to osmotic lysis caused by non-saturated intracellular buildup of the compound. L-DABA's deleterious effects can be removed by incubating it with L-alanine and L-methionine at the same time [1]. Kinetic investigations show that L-DABA is a non-linear, non-competitive inhibitor of GABA transaminase activity. The rise in GABA levels induced by L-DABA is consistent with the suppression of GABA transaminase activity [2]. L-2,4-diaminobutyric acid is an amino acid analog that has cytotoxic effects on the human glioma cell line SKMG-1 and normal human fibroblasts. The L-DABA concentration needed to reduce cell counts to 50% of control after 24 hours of incubation at 37°C is 12.5 mM for human fibroblasts and 20 mM for glioma cell lines [3].
L-DABA exhibited potent and irreversible cytolytic activity against mouse fibrosarcoma cells in culture. Incubation with 10 mM L-DABA for 24 hours at 37°C resulted in 100% lysis of the tumor cells, as determined by lactate dehydrogenase (LD) release. The time required for 50% lysis (LT₅₀) was approximately 7-8 hours. [1] The cytolytic effect was concentration-dependent. A concentration of 5 mM L-DABA induced only limited cell damage even after 48 hours of incubation, indicating a sharp threshold for the lytic effect between 5 and 10 mM. [1] The cytotoxic effect of 10 mM L-DABA was completely abolished by the simultaneous addition of 10 mM each of L-alanine and L-methionine, which compete with L-DABA for transport via System A. The D-isomers of alanine and methionine, as well as sarcosine (N-methylglycine), showed much weaker protective effects. [1] The proposed mechanism of action is osmotic lysis of the cells, likely combined with a lowered intracellular adenylate charge, resulting from the energy-dependent, non-saturable intracellular accumulation of L-DABA via System A transport. [1] |
| ln Vivo |
Treatment with L-DABA can stop tumor growth by 43.4%[1]. In vivo, L-DABA inhibits GABA transaminase more potently than it does in vitro [2].
In mice bearing subcutaneous transplants of mouse fibrosarcoma cells, intraperitoneal (i.p.) administration of an isotonic 0.1 M (100 mM) L-DABA solution significantly reduced tumor growth. [1] Across six experimental series involving a total of 90 mice, the mean tumor weight in 42 evaluable L-DABA-treated animals was 1.16 g (± 0.77 g), compared to 2.05 g (± 1.22 g) in 27 untreated control animals. This represents an average tumor weight reduction of 43.4%. The extent of reduction varied between series (8.3% to 61.5%) depending on the treatment regimen. [1] Treatment did not lead to complete tumor regression, and local recurrences were observed in 5 out of 7 animals from which tumors were surgically removed after L-DABA treatment. [1] |
| Cell Assay |
Cell Culture: Mouse fibrosarcoma cells were routinely grown in Eagle's Minimum Essential Medium (MEM) supplemented with 10% fetal calf serum and antibiotics (penicillin and streptomycin) at 37°C in a humidified atmosphere with 5% CO₂. [1]
Cytolysis Assay: For experiments, cells were seeded into culture dishes and allowed to grow for 24 hours. The culture medium was then replaced with a simplified serum-free MEM. L-DABA was added to this medium at final concentrations ranging from 1 to 20 mM (typically 10 mM), either alone or in combination with other amino acids (e.g., L-alanine, L-methionine, their D-isomers, or sarcosine) at 10 mM each. The osmolarity of the incubation medium was adjusted. Cells were incubated with the compounds for periods ranging from 4 to 48 hours (typically 24 hours) at 37°C. [1] Viability Assessment: After incubation, cell viability was assessed by light microscopy. The culture supernatants were collected, and cell lysis was quantified by measuring the activity of lactate dehydrogenase (LD) released into the medium. Total cellular LD activity was determined from a separate sample of cells lysed by hypotonic shock combined with freeze-thawing. The percentage of cell lysis was calculated by comparing the LD activity in the test supernatant (corrected for background from control cells) to the total cellular LD activity. [1] |
| Animal Protocol |
Animals and Tumor Model: Adult male NMR1 mice (weighing ~35 g) were used. Mouse fibrosarcoma cells (5 × 10⁷ cells) were transplanted subcutaneously into the right flank of anesthetized mice via a small incision. [1]
Drug Formulation and Administration: L-DABA (dihydrochloride form) was dissolved in water to prepare a 0.1 M (100 mM) solution. The pH was adjusted to 7.4 with sodium hydroxide, resulting in an isotonic solution (~300-310 mOsm). [1] Treatment Regimen: Treatment began 1 to 4 days after tumor transplantation. Mice received intraperitoneal (i.p.) injections of the 0.1 M L-DABA solution daily. The injected volume (dose) was typically between 0.50 ml and 0.90 ml (50-90 µmol of DAB) per injection, administered as a single daily dose in most series. The total treatment period ranged from 8 to 23 days across different experimental series. [1] Dose Adjustment: The dosage was individualized based on the animal's clinical condition and weight change. Treatment was withheld or the dose reduced if an animal lost more than 0.5-2.0 g of body weight per 24 hours, and resumed only after weight recovery. [1] Endpoint: Animals were euthanized 2-12 days after the last treatment, when tumors in control mice reached approximately 10% of the total body weight. Solid tumors were excised and weighed. [1] |
| Toxicity/Toxicokinetics |
Treatment-related mortality: In vivo injection of L-DABA resulted in significant toxicity. Of the 61 mice treated across all series, 17 (27.9%) died during treatment. Mortality rates varied depending on the administration regimen. [1] Weight loss: L-DABA treatment resulted in persistent weight loss in the animals, at least in part attributable to loss of appetite. [1] Neurotoxicity: Some treated animals exhibited specific neurological symptoms, including varying degrees of tonic-spasm, tail and limb rigidity, incoordination and twitching, and increased tactile sensitivity. Somnolence was also a common symptom. These symptoms were usually reversible 1–3 days after discontinuation of L-DABA. [1] Speculated mechanism of toxicity: Neurotoxicity symptoms may be caused by ammonia poisoning due to L-DABA deamination or by increased GABA levels in the brain due to L-DABA inhibition of GABA transaminase. However, these mechanisms were not experimentally confirmed in this study. [1]
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| References | |
| Additional Infomation |
L-2,4-Diaminobutyric acid (L-DABA) is a 2,4-diaminobutyric acid with an S configuration. It is a plant metabolite that is functionally related to butyric acid. It is the conjugate base of L-2,4-diazabutyrate, the conjugate acid of L-2,4-diaminobutyrate, and the enantiomer of D-2,4-diaminobutyric acid. L-2,4-Diaminobutyric acid has been reported to be found in broadleaf pea (Lathyrus latifolius), Streptomyces albidoflavus, and other organisms with relevant data. L-DABA is a non-metabolizable diamino acid analog. [1] Its antitumor effect is considered unique among chemotherapeutic drugs because it primarily targets the plasma membrane transport system (A system), leading to osmotic dissolution rather than interfering with DNA synthesis or other intracellular processes. [1]
Due to the significant systemic toxicity observed in this study (weight loss, neurotoxicity, lethality), the authors concluded that the limitation of L-DABA as an anti-tumor drug alone lies in its limited efficacy. However, they believe that its unique mechanism of action may offer new possibilities for combination therapy with other drugs that target different subcellular targets. [1] This study also hypothesizes that potential qualitative differences in A system transporters between normal and malignant cells (e.g., sensitivity to thiol reactants) may be used in future therapeutic strategies to achieve selective toxicity to tumor cells. [1] |
| Molecular Formula |
C4H10N2O2.HBR
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|---|---|
| Molecular Weight |
199.04634
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| Exact Mass |
118.074
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| CAS # |
1758-80-1
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| Related CAS # |
(S)-L-DABA dihydrochloride;1883-09-6
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| PubChem CID |
134490
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| Appearance |
White to off-white solid powder
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| Density |
1.218 g/cm3
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| Boiling Point |
321ºC at 760 mmHg
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| Flash Point |
147.9ºC
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| Vapour Pressure |
6.36E-05mmHg at 25°C
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| Index of Refraction |
1.513
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| LogP |
1.105
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
8
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| Complexity |
84.1
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C(CN)[C@@H](C(=O)O)N
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| InChi Key |
OGNSCSPNOLGXSM-VKHMYHEASA-N
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| InChi Code |
InChI=1S/C4H10N2O2/c5-2-1-3(6)4(7)8/h3H,1-2,5-6H2,(H,7,8)/t3-/m0/s1
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| Chemical Name |
(2S)-2,4-diaminobutanoic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ~1 mg/mL (~8.47 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (846.53 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.0239 mL | 25.1193 mL | 50.2386 mL | |
| 5 mM | 1.0048 mL | 5.0239 mL | 10.0477 mL | |
| 10 mM | 0.5024 mL | 2.5119 mL | 5.0239 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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