| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
IC50: 5.5 nM (soluble Adenylyl Cyclase)[1]
Soluble adenylyl cyclase (sAC, ADCY10). TDI-11861 is a potent and selective inhibitor of sAC. It inhibits sAC activity with high potency, demonstrating an IC50 of 3.3 nM in biochemical assays and 5.5 nM in cellular assays, with a Kd of 1.4 nM. Its slow dissociation rate ensures prolonged inhibition, which is a key feature for studying sAC function. |
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| ln Vitro |
TDI-11861 demonstrates potent inhibitory activity against soluble adenylyl cyclase (sAC). In biochemical assays, it has an IC50 of 3.3 nM, and in cellular assays, it shows an IC50 of 5.5 nM. It binds to sAC with a high affinity, as indicated by a Kd of 1.4 nM. The compound's slow dissociation rates contribute to its sustained inhibitory effect, making it a powerful tool for sAC research.
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| ln Vivo |
In vivo, TDI-11861 is used to investigate the physiological and pathophysiological roles of sAC. As a potent and selective inhibitor, it can be administered to animal models to study the effects of sAC blockade on various systems, such as male fertility, where sAC is a critical regulator of sperm function, or in metabolic disorders where sAC signaling is implicated.
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| Enzyme Assay |
The in vitro activity of TDI-11861 against sAC is typically determined using enzyme activity assays. Recombinant sAC enzyme is incubated with its substrate, ATP, in the presence of varying concentrations of the inhibitor. The production of cAMP, the product of the reaction, is then measured using a luminescent or fluorescent detection method. This allows for the determination of the compound's IC50 (3.3 nM) and its inhibition kinetics.
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| Cell Assay |
Cellular assays for sAC inhibition involve treating cells that endogenously express sAC with TDI-11861. Following treatment, the intracellular cAMP levels are measured to assess the compound's ability to inhibit sAC activity within a cellular context. This approach confirms that the compound can effectively penetrate cells and inhibit its target, with an observed cellular IC50 of 5.5 nM.
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| Animal Protocol |
In vivo studies with TDI-11861 are typically performed in animal models to explore sAC function. For example, in male fertility research, the compound could be administered to mice, and its effects on sperm motility and fertilization capacity would be assessed. The slow dissociation rate of TDI-11861 suggests it would provide a sustained blockade of sAC in vivo, making it suitable for prolonged studies.
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| ADME/Pharmacokinetics |
TDI-11861 is a small molecule with the molecular formula C22H25ClF2N6O3. Its pharmacokinetic properties, such as oral bioavailability and half-life, would be key factors in its utility for in vivo studies. As a research compound with high potency (IC50 3.3-5.5 nM) and slow dissociation rates, it is designed for effective target engagement, which is a critical aspect of its pharmacodynamic profile.
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| Toxicity/Toxicokinetics |
No specific toxicity data is available for TDI-11861. As a potent enzyme inhibitor, its safety profile would be an important consideration. Potential off-target effects could lead to toxicity, and standard preclinical safety studies would be needed to evaluate its safety margin. Its high selectivity for sAC would be expected to minimize off-target toxicity, but this would need to be confirmed experimentally.
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| References | |
| Additional Infomation |
TDI-11861 (CAS#: 2857049-72-8) is a second-generation, potent, and selective inhibitor of soluble adenylyl cyclase (sAC). It has an IC50 of 3.3 nM in biochemical assays and 5.5 nM in cellular assays. The compound is characterized by a slow dissociation rate and is used as a research tool to study sAC biology. It is not approved for clinical use and is intended for research purposes only.
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| Molecular Formula |
C22H25CLF2N6O3
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|---|---|
| Molecular Weight |
494.922110319138
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| Exact Mass |
494.164
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| CAS # |
2857049-72-8
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| PubChem CID |
166101565
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| Appearance |
White to off-white solid powder
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
34
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| Complexity |
629
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| Defined Atom Stereocenter Count |
1
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| SMILES |
N1(CCOC2=CC=CC=C2CC2=CN(C(F)F)N=C2C2C=C(Cl)N=C(N)N=2)CCOC[C@H]1CO
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| InChi Key |
XVGSKZXXLKUEIO-MRXNPFEDSA-N
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| InChi Code |
InChI=1S/C22H25ClF2N6O3/c23-19-10-17(27-22(26)28-19)20-15(11-31(29-20)21(24)25)9-14-3-1-2-4-18(14)34-8-6-30-5-7-33-13-16(30)12-32/h1-4,10-11,16,21,32H,5-9,12-13H2,(H2,26,27,28)/t16-/m1/s1
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| Chemical Name |
[(3R)-4-[2-[2-[[3-(2-amino-6-chloropyrimidin-4-yl)-1-(difluoromethyl)pyrazol-4-yl]methyl]phenoxy]ethyl]morpholin-3-yl]methanol
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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: 50 mg/mL (101.03 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0205 mL | 10.1026 mL | 20.2053 mL | |
| 5 mM | 0.4041 mL | 2.0205 mL | 4.0411 mL | |
| 10 mM | 0.2021 mL | 1.0103 mL | 2.0205 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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