| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 195 nM (sAC)[2].
Soluble adenylyl cyclase (sAC, ADCY10). TDI-10229 is a selective inhibitor of sAC, which produces cyclic AMP (cAMP) in response to bicarbonate and calcium signals. It exhibits selectivity for sAC over transmembrane adenylyl cyclases (AC1-3, -5, -8, -9). |
|---|---|
| ln Vitro |
Based on human 4-4 cells, TDI-10229 exhibits good permeability, with an IC50 of 92 nM [2].
In a cell-free assay using human sAC, TDI-10229 has an IC50 of 0.2 uM. In HEK293 cells expressing rodent sAC, it inhibits IBMX-induced cAMP accumulation with an IC50 of 0.1 uM, confirming potent cellular target engagement. |
| ln Vivo |
Cmax, AUC, and MRT for TDI-10229 (5 mg/kg; po) dosing were 15.5 μM, 94 μg h/mL, and 3.95 hours, respectively.
At 5 uM, TDI-10229 inhibits capacitation-induced cAMP accumulation and protein kinase A (PKA) activation in isolated mouse and human sperm. It also prevents the acrosome reaction and fertilization of mouse oocytes in vitro, demonstrating its functional effects on sperm biology. |
| Enzyme Assay |
A cell-free assay is performed using purified recombinant human sAC enzyme. The enzyme is incubated in a reaction buffer containing bicarbonate, ATP, and varying concentrations of TDI-10229. After incubation, the amount of cAMP produced is quantified using a homogeneous time-resolved fluorescence (HTRF) or chemiluminescent cAMP detection kit to calculate the IC50 (0.2 uM).
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| Cell Assay |
HEK293 cells expressing rodent sAC are seeded in 96-well plates. Cells are pre-incubated with varying concentrations of TDI-10229, then stimulated with the phosphodiesterase inhibitor IBMX to induce cAMP accumulation. After lysis, intracellular cAMP levels are measured using a competitive immunoassay to determine the cellular IC50 (0.1 uM).
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| Animal Protocol |
Animal/Disease Models: Mouse[2]
Doses: 20 mg/kg Route of Administration: Po(pharmacokinetic/PK Analysis) Experimental Results: The Cmax, AUC and MRT were 15.5 μM, 94 μg h/mL and 3.95 hrs (hours), respectively. Pharmacodynamic studies in mice are performed by oral gavage of TDI-10229. The compound is administered at 20 mg/kg, and its effect on sAC activity is assessed by measuring cAMP levels in relevant tissues (e.g., testes) at various time points post-dose, providing an in vivo target engagement readout. |
| ADME/Pharmacokinetics |
Following an oral dose of 5 mg/kg TDI-10229 in mice, pharmacokinetic parameters were measured: Cmax = 15.5 uM, AUC = 94 ug·h/mL, and MRT = 3.95 hours. These properties demonstrate sufficient oral bioavailability and systemic exposure to support its use as an in vivo tool compound.
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| Toxicity/Toxicokinetics |
Not reported. The toxicological profile of TDI-10229 has not been fully characterized. However, given its high specificity for sAC, it is expected to have a favorable safety profile. sAC knockout mice are viable, indicating that sAC inhibition may be well-tolerated, although long-term effects require further study.
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| References |
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| Additional Infomation |
TDI-10229 was developed through a discovery campaign resulting in a potent and orally bioavailable sAC inhibitor. It is a critical tool for studying the many functions of sAC, which is involved in processes ranging from sperm maturation and fertilization to the regulation of intraocular pressure and the cellular response to metabolic stress. Its selectivity over transmembrane adenylyl cyclases makes it particularly valuable for dissecting sAC-specific signaling.
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| Molecular Formula |
C16H16CLN5
|
|---|---|
| Molecular Weight |
313.784741401672
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| Exact Mass |
313.109
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| CAS # |
2810887-45-5
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| PubChem CID |
156612922
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| Appearance |
White to off-white solid powder
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
22
|
| Complexity |
362
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1(N)=NC(C2C(CC3=CC=CC=C3)=C(C)N(C)N=2)=CC(Cl)=N1
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| InChi Key |
VSMTYSWGHKYXOF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H16ClN5/c1-10-12(8-11-6-4-3-5-7-11)15(21-22(10)2)13-9-14(17)20-16(18)19-13/h3-7,9H,8H2,1-2H3,(H2,18,19,20)
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| Chemical Name |
4-(4-benzyl-1,5-dimethylpyrazol-3-yl)-6-chloropyrimidin-2-amine
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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 (398.37 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.63 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.63 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 | 3.1869 mL | 15.9347 mL | 31.8695 mL | |
| 5 mM | 0.6374 mL | 3.1869 mL | 6.3739 mL | |
| 10 mM | 0.3187 mL | 1.5935 mL | 3.1869 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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