| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
IC50: 1.49 nM (Sepiapterin reductase)[1]
Sepiapterin reductase (SPR), an enzyme involved in the biosynthesis of tetrahydrobiopterin (BH4). BH4 is an essential cofactor for aromatic amino acid hydroxylases (phenylalanine, tyrosine, tryptophan) and nitric oxide synthases (NOS). By inhibiting SPR, QM385 reduces BH4 levels, which in turn affects T-cell metabolism and proliferation. It has an IC50 of 1.49 nM for SPR inhibition. |
|---|---|
| ln Vitro |
At modest concentrations, QM385 efficiently suppresses human CD4+ T cell proliferation[1].
QM385 is a potent inhibitor of sepiapterin reductase (SPR) with an IC50 of 1.49 nM. It effectively inhibits the proliferation of human CD4+ T cells in vitro at low nanomolar concentrations. This anti-proliferative effect is a result of limiting tetrahydrobiopterin (BH4) production, which impacts the metabolic pathways required for T-cell activation and expansion, including possibly affecting phenylalanine hydroxylase or other BH4-dependent processes. |
| ln Vivo |
In vivo, QM385 has demonstrated potent immunomodulatory effects. It blocks T-cell proliferation and autoimmunity with nanomolar potency. Because it is orally available, it can be administered to animals to study its effects on immune-mediated diseases. It has been shown to effectively inhibit the proliferation of human CD4+ T cells, which are central players in autoimmune conditions like multiple sclerosis, rheumatoid arthritis, and lupus.
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| Enzyme Assay |
A standard biochemical assay for sepiapterin reductase (SPR) involves monitoring the reduction of the substrate sepiapterin to 7,8-dihydrobiopterin (BH2) using NADPH as a cofactor. The enzyme reaction is performed in a buffer containing recombinant SPR, sepiapterin, NADPH, and varying concentrations of the inhibitor. The reaction can be followed by measuring the decrease in absorbance of NADPH at 340 nm (as it is oxidized to NADP+) or by fluorescence detection of the product. The IC50 of QM385 is calculated from the inhibition curve.
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| Cell Assay |
A standard cellular assay for QM385 is measuring its effect on CD4+ T-cell proliferation. Human peripheral blood mononuclear cells (PBMCs) are isolated, and CD4+ T cells are purified. Cells are stimulated with anti-CD3/CD28 antibodies or a mitogen like PHA. They are treated with varying concentrations of QM385 (e.g., 0.1-100 nM). After 48-72 hours, cell proliferation is measured by 3H-thymidine incorporation or by a colorimetric method (e.g., CFSE dilution measured by flow cytometry). Cytokine production (e.g., IFN-gamma, IL-17, TNF-alpha) can also be measured by ELISA.
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| Animal Protocol |
The in vivo efficacy of QM385 is typically assessed in a mouse model of autoimmune disease, such as Experimental Autoimmune Encephalomyelitis (EAE), which models multiple sclerosis. Mice are immunized with myelin antigens to induce the disease. QM385 is then administered to the mice, typically via oral gavage, at the onset of symptoms or before. Mice are scored daily for clinical signs of EAE (paralysis of the tail and limbs). At the end of the study, T-cell responses (proliferation and cytokine production) are analyzed ex vivo, and spinal cord histology is examined for demyelination and inflammation.
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| ADME/Pharmacokinetics |
QM385 is an orally available compound with good oral bioavailability (F). This is a critical feature, as it allows for convenient dosing in animal models. The compound is a small molecule with an IC50 of 1.49 nM, making it highly potent. Specific pharmacokinetic parameters (such as T1/2, Cmax, AUC) are not detailed in the standard literature, but its design for oral administration and potent in vivo activity indicates favorable drug-like properties. The high potency (IC50 = 1.49 nM) is reported as binding IC50.
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| Toxicity/Toxicokinetics |
Specific toxicological data for QM385 is not available in standard research literature. As a potent inhibitor of a key metabolic enzyme involved in neurotransmitter synthesis (via BH4 cofactor for phenylalanine, tyrosine, and tryptophan hydroxylases), on-target toxicity could be significant, potentially affecting mood, cognition, and cardiovascular function (via nitric oxide synthases). It was developed to target T-cell autoimmunity, and at effective doses, it is well-tolerated enough for research applications. A full toxicology panel would be required for clinical development.
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| References |
[1]. Cronin SJF, et al. The metabolite BH4 controls T cell proliferation in autoimmunity and cancer. Nature. 2018 Nov;563(7732):564-568.
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| Additional Infomation |
QM385 is a research chemical tool and a potent inhibitor of sepiapterin reductase (SPR) with high selectivity and oral bioavailability. Sepiapterin reductase is an enzyme in the biosynthesis pathway of tetrahydrobiopterin (BH4). BH4 is an essential cofactor for several enzymes, including the nitric oxide synthases (NOS) and the aromatic amino acid hydroxylases. By inhibiting SPR, QM385 reduces BH4 availability. T-cells have a high metabolic demand for BH4 upon activation, and limiting BH4 suppresses their proliferation. This compound is being investigated preclinically for its potential to treat autoimmune diseases where T-cells play a key pathogenic role. QM385 is not an approved drug and is for research use only. Its CAS number is 2093421-02-2.
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| Molecular Formula |
C17H18F3N7O2
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|---|---|
| Molecular Weight |
409.37
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| Exact Mass |
409.147
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| CAS # |
2093421-02-2
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| PubChem CID |
137049058
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.59±0.1 g/cm3(Predicted)
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| Boiling Point |
586.1±60.0 °C(Predicted)
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| LogP |
1.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
29
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| Complexity |
693
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(CN1CCN(C(C2C=NN(C3=NN4C=CC=C4C(N3)=O)C=2C)=O)CC1)(F)F
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| InChi Key |
GPMQVMCLRRPIIE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H18F3N7O2/c1-11-12(15(29)25-7-5-24(6-8-25)10-17(18,19)20)9-21-27(11)16-22-14(28)13-3-2-4-26(13)23-16/h2-4,9H,5-8,10H2,1H3,(H,22,23,28)
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| Chemical Name |
2-[5-methyl-4-[4-(2,2,2-trifluoroethyl)piperazine-1-carbonyl]pyrazol-1-yl]-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one
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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) |
DMSO: 125 mg/mL (305.35 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.08 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4428 mL | 12.2139 mL | 24.4278 mL | |
| 5 mM | 0.4886 mL | 2.4428 mL | 4.8856 mL | |
| 10 mM | 0.2443 mL | 1.2214 mL | 2.4428 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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