| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
| Targets |
VTP-27999 targets renin, an aspartic protease that is the rate-limiting enzyme in the renin-angiotensin system (RAS). Renin is secreted by the juxtaglomerular cells of the kidney and catalyzes the cleavage of angiotensinogen to angiotensin I. Angiotensin I is subsequently converted to angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II is a potent vasoconstrictor that plays a central role in blood pressure regulation and fluid homeostasis. By inhibiting renin, VTP-27999 reduces the production of angiotensin I and subsequently angiotensin II, thereby lowering blood pressure. The compound is an alkyl amine-based renin inhibitor.
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| ln Vitro |
VTP-27999 demonstrates potent in vitro activity as a renin inhibitor. The compound inhibits renin activity in enzymatic assays, reducing the production of angiotensin I from angiotensinogen. Its activity is concentration-dependent, with potent inhibition observed at appropriate concentrations. VTP-27999 is an alkyl amine-based renin inhibitor. The compound's in vitro activity has been characterized in various assay systems. Its potency and selectivity for renin make it a valuable tool for studying the renin-angiotensin system and evaluating renin inhibition as a therapeutic strategy for hypertension and related conditions. The compound's hydrochloride salt form improves solubility for research applications.
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| ln Vivo |
In vivo, VTP-27999 has been studied for its effects on blood pressure and the renin-angiotensin system. As a renin inhibitor, the compound reduces angiotensin II levels and lowers blood pressure. VTP-27999 is useful for hypertension and end-organ diseases. The compound's in vivo activity has been characterized in various animal models of hypertension. Its oral bioavailability makes it suitable for convenient dosing in research settings. The compound's effects on blood pressure and end-organ protection have been evaluated in preclinical studies. Comprehensive in vivo efficacy data are available from research publications.
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| Enzyme Assay |
In vitro enzyme assays for VTP-27999 involve measuring the inhibition of renin activity. Recombinant or purified renin is incubated with varying concentrations of the test compound and its substrate, angiotensinogen. The production of angiotensin I is quantified by radioimmunoassay, ELISA, or LC-MS/MS. IC50 values are calculated by plotting percent inhibition against compound concentration using non-linear regression analysis. The compound is an alkyl amine-based renin inhibitor. Selectivity assays compare the compound's activity against other aspartic proteases such as cathepsin D and pepsin. The assay is performed in appropriate buffer conditions with controls for non-specific inhibition. Each concentration is typically tested in duplicate or triplicate.
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| Cell Assay |
In vitro cellular assays for VTP-27999 are performed using cells that express components of the renin-angiotensin system. Cells such as renin-producing cells or angiotensinogen-expressing cells can be used. Alternatively, assays using plasma or serum containing endogenous renin and angiotensinogen can be performed. Cells or plasma are incubated with varying concentrations of the compound, and angiotensin I production is measured by ELISA or radioimmunoassay. Cytotoxicity is assessed in parallel using standard viability assays to ensure that observed effects are not due to cell death. IC50 values for inhibition of angiotensin I production are calculated from dose-response curves. The compound's effects on downstream angiotensin II production can also be assessed.
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| Animal Protocol |
In vivo animal studies for VTP-27999 are conducted using rodent models of hypertension, such as spontaneously hypertensive rats (SHR) or angiotensin II-induced hypertensive models. The compound is administered via oral gavage at various doses and schedules. Blood pressure is measured using telemetry or tail-cuff plethysmography. Plasma renin activity and angiotensin II levels are measured to confirm target engagement. End-organ protection is assessed by evaluating renal function, cardiac function, and vascular remodeling. Pharmacokinetic studies assess drug concentrations in plasma. Animals are monitored for clinical signs and body weight. Efficacy is expressed as reduction in blood pressure and improvement in end-organ parameters compared to vehicle-treated controls.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of VTP-27999 Hydrochloride have been characterized in preclinical studies. The compound has a molecular formula of C26H42Cl2N4O5 and a molecular weight of 561.54 g/mol. Its IUPAC name is methyl (2-((R)-(3-chlorophenyl)((R)-1-(((S)-2-(methylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propyl)carbamoyl)piperidin-3-yl)methoxy)ethyl)carbamate hydrochloride. The compound is soluble in water (10 mM in water). Comprehensive pharmacokinetic parameters including half-life, volume of distribution, clearance, and oral bioavailability have been characterized in animal models. The compound's pharmacokinetic profile supports its use in preclinical studies of hypertension. Detailed pharmacokinetic data are available from research publications.
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| Toxicity/Toxicokinetics |
VTP-27999 Hydrochloride is intended for laboratory research use only and has not undergone comprehensive clinical toxicology testing. As a renin inhibitor that lowers blood pressure, the compound would be expected to have effects on hemodynamics and renal function. Standard in vitro cytotoxicity assays in cell lines are typically performed alongside efficacy studies to rule out nonspecific toxicity. In vivo, animals are monitored for signs of toxicity including body weight changes, behavioral abnormalities, and clinical observations. Comprehensive toxicological characterization including genotoxicity, cardiotoxicity, and repeated-dose toxicity studies has been conducted as part of preclinical development. The compound is not approved for human use and is strictly intended for research purposes.
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| References | |
| Additional Infomation |
VTP-27999 Hydrochloride is an alkyl amine-based renin inhibitor useful for hypertension and end-organ diseases. It has a molecular formula of C26H42Cl2N4O5 and a molecular weight of 561.54 g/mol. VTP-27999 reduces angiotensin II levels by inhibiting the rate-limiting enzyme renin in the renin-angiotensin system. The compound is soluble in water (10 mM). VTP-27999 has not entered clinical trials and has not received regulatory approval for any indication. It is available from research chemical suppliers for non-clinical research purposes only. VTP-27999 is a valuable research tool for studying the renin-angiotensin system and developing new therapies for hypertension and related cardiovascular diseases.
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| Molecular Formula |
C₂₆H₄₂CL₂N₄O₅
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|---|---|
| Molecular Weight |
561.54
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| Exact Mass |
560.253
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| CAS # |
1264191-73-2
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| Related CAS # |
VTP-27999 TFA;1013937-63-7;VTP-27999;942142-51-0
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| PubChem CID |
66577067
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| Appearance |
White to yellow solid powder
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| LogP |
5.119
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
37
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| Complexity |
672
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CN[C@@H](C[C@H]1CCCOC1)CNC(=O)N2CCC[C@H](C2)[C@H](C3=CC(=CC=C3)Cl)OCCNC(=O)OC.Cl
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| InChi Key |
XDXSPYSCCJMHRQ-VIEYARBJSA-N
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| InChi Code |
InChI=1S/C26H41ClN4O5.ClH/c1-28-23(14-19-6-5-12-35-18-19)16-30-25(32)31-11-4-8-21(17-31)24(20-7-3-9-22(27)15-20)36-13-10-29-26(33)34-2;/h3,7,9,15,19,21,23-24,28H,4-6,8,10-14,16-18H2,1-2H3,(H,29,33)(H,30,32);1H/t19-,21-,23+,24+;/m1./s1
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| Chemical Name |
methyl N-[2-[(R)-(3-chlorophenyl)-[(3R)-1-[[(2S)-2-(methylamino)-3-[(3R)-oxan-3-yl]propyl]carbamoyl]piperidin-3-yl]methoxy]ethyl]carbamate;hydrochloride
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| Synonyms |
VTP-27999 HCl VTP 27999VTP27999
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ≥ 100 mg/mL (~178.08 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 | 1.7808 mL | 8.9041 mL | 17.8082 mL | |
| 5 mM | 0.3562 mL | 1.7808 mL | 3.5616 mL | |
| 10 mM | 0.1781 mL | 0.8904 mL | 1.7808 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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