| ln Vitro |
TASP0434299 (60 min) effectively inhibited the binding of [3H]AVP to the cell membrane of 293FT cells expressing human V1B receptor, with an IC50 value of 0.526 nM [2]. TASP0434299 (60 min) effectively inhibited the binding of [3H]AVP to the anterior pituitary membrane of rats expressing endogenous rat V1B receptor, with an IC50 value of 0.641 nM [2]. TASP0434299 (30 min) effectively antagonized the increase of [Ca2+]ᵢ induced by AVP in K1 cells of Chinese hamster ovaries expressing human V1B receptor, with an IC50 value of 0.639 nM [2]. TASP0434299 (1 μM) is a substrate of human P-glycoprotein, and its efflux ratio was 27.9 when detected at a concentration of 1 μM in LLC-GA5-COL300 cells [2]. TASP0434299 (1 μM; co-incubated with [3H]TASP0434299 for 120 min) completely blocked the specific binding of [3H]TASP0434299 to the native V1B receptor in rat anterior pituitary slices [2]. TASP0434299 (1 μM; co-incubated with [3H]TASP0434299 for 120 min) completely blocked the specific binding of [3H]TASP0434299 to the native V1B receptor in rhesus monkey anterior pituitary slices [2]. TASP0434299 binds efficiently and selectively to human V1B receptors with an IC50 of 0.526 nM and has no detectable affinity for human V1A, V2 or oxytocin receptors [3]. TASP0434299 can effectively antagonize intracellular calcium mobilization mediated by human V1B receptor, with an IC50 of 0.639 nM[3].
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|---|---|
| ln Vivo |
[3H]TASP0434299 (0.93 nM/kg; intravenous injection; single dose) binds specifically and saturably to V1B receptors in the anterior pituitary of rats [2]. 11C-TASP0434299 (0.01–10.7 mg/kg; intravenous injection; single dose) binds specifically to endogenous angiotensin V1B receptors in the pituitary of rhesus monkeys [3].
|
| Animal Protocol |
Animal/Disease Models:Sprague-Dawley mice (male, weight 234.9–293.4 g)[2]
Doses: 0.93 nM/kg ([3H] labeled); 0.41, 0.80, 1.9, 4.2, 8.7 nmol/kg (unlabeled, combined administration) Route of Administration: Intravenous injection Experimental Results: Specific membrane-bound radioactivity was detected in the anterior pituitary, peaking at 30 minutes post-injection and gradually decreasing over 90 minutes. Negligible radioactivity was observed in the eye and cerebellum. Saturable membrane-bound radioactivity was confirmed in the anterior pituitary, with an estimated B_max of 18,300 dpm/mg protein (equivalent to 96 fmol/mg protein), matching the in vitro B_max of rat V1B receptors. Animal/Disease Models:Rhesus macaque (male, 5.2–6.5 kg) [3] Doses: 406 MBq (radioactive, range 361–467 MBq); 6.1 μg (mass dose, range 2.9–10 μg) Route of Administration: Intravenous Injection Experimental Results: 90 minutes after injection, the pituitary SUV value reached approximately 2.0. The balance ratio of specific uptake to non-replacement uptake was approximately 1.6. Compared with the pituitary, the radioactive uptake and retention in the temporalis muscle were significantly reduced. Radioactivity in the brain tissue was almost negligible. |
| References |
| Molecular Formula |
C27H35N5O5
|
|---|---|
| Molecular Weight |
509.61
|
| CAS # |
1520893-08-6
|
| Appearance |
Typically exists as solids at room temperature
|
| SMILES |
O=C1C2=CC(OCCCN3CCOCC3)=CN=C2N=C(C=4C=CC=C(OC)C4)N1CC(=O)NC(C)(C)C
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 1.9623 mL | 9.8114 mL | 19.6228 mL | |
| 5 mM | 0.3925 mL | 1.9623 mL | 3.9246 mL | |
| 10 mM | 0.1962 mL | 0.9811 mL | 1.9623 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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