| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| Other Sizes |
|
Purity: ≥98%
MK-7145 is a novel, potent, selective and orally bioactive ROMK inhibitor with IC50 of 0.045 μM and has the potential for the treatment of hypertension and heart failure. ROMK, the renal outer medullary potassium channel, is involved in potassium recycling at the thick ascending loop of Henle and potassium secretion at the cortical collecting duct in the kidney nephron. Because of this dual site of action, selective inhibitors of ROMK are expected to represent a new class of diuretics/natriuretics with superior efficacy and reduced urinary loss of potassium compared to standard-of-care loop and thiazide diuretics. MK-7145 is selective against other cardiac ion channels such as Cav1.2 and Nav1.5 (IC50 > 30 μM). MK-7145 was not a potent reversible inhibitor of human CYP3A4, CYP2C9, or CYP2D6 (IC50 > 50μM) and was not a time-dependent inhibitor of CYP3A4 at 10and 50 μM. MK-7145 caused dose-dependent lowering of blood pressure in a subchronic SHR model. MK-7145 is the first small molecule ROMK inhibitor to enter clinical development.
| ln Vitro |
MK-7145 (compound 12) was evaluated against other Kir channel family members. Even at doses as high as 30 μM, it shows no discernible action on the Kir2.1, Kir2.3, Kir4.1, or Kir7.1 channels. Additionally, MK-7145 exhibits selectivity for additional cardiac ion channels, including Nav1.5 and Cav1.2 (IC50>30 μM). Using HEK293 cells that were transfected with human SERT, MK-7145 inhibited 3H-serotonin uptake with an IC50 value of 2.40±0.32 μM (n=5). This was based on an extensive counterscreen panel that included over 150 receptors, enzymes, and ion channels. Only three activities at <10 μM were shown by MK-7145: acetylcholinesterase, ACES, IC50=9.94 μM, growth inhibitory isoform 1, sst1, IC50=2.63 μM, and human serotonin transporter, SERT, IC50=0.12 μM. Because MK-7145 is a substrate of human Pgp (human Mdr1 BAAB ratio = 12), in addition to its greater ROMK potency and in vivo efficiency, it should offer a sizable safety window for SERT off-target activities.
|
|---|---|
| References |
[1]. Tang H, et al. Discovery of MK-7145, an Oral Small Molecule ROMK Inhibitor for the Treatment of Hypertension and Heart Failure. ACS Med Chem Lett. 2016 May 12;7(7):697-701.
|
| Molecular Formula |
C26H30N2O6
|
|---|---|
| Molecular Weight |
466.526
|
| CAS # |
1255204-84-2
|
| Related CAS # |
1255204-84-2;1255204-85-3 (2HCl);
|
| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
|
| SMILES |
O[C@H](C1=CC=C(C(OC2)=O)C2=C1C)CN3CCN(C[C@H](O)C4=CC=C(C(OC5)=O)C5=C4C)CC3
|
| InChi Key |
OCKGFTQIICXDQW-ZEQRLZLVSA-N
|
| InChi Code |
InChI=1S/C26H30N2O6/c1-15-17(3-5-19-21(15)13-33-25(19)31)23(29)11-27-7-9-28(10-8-27)12-24(30)18-4-6-20-22(16(18)2)14-34-26(20)32/h3-6,23-24,29-30H,7-14H2,1-2H3/t23-,24-/m0/s1
|
| Chemical Name |
5,5'-((1R,1'R)-piperazine-1,4-diylbis(1-hydroxyethane-2,1-diyl))bis(4-methylisobenzofuran-1(3H)-one)
|
| Synonyms |
MK-7145; MK 7145; MK7145.
|
| 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 | 2.1435 mL | 10.7174 mL | 21.4348 mL | |
| 5 mM | 0.4287 mL | 2.1435 mL | 4.2870 mL | |
| 10 mM | 0.2143 mL | 1.0717 mL | 2.1435 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.
α-Substitution in the piperazine carboxamide series.ACS Med Chem Lett.2016 May 12;7(7):697-701. |
|---|
α-Substitution in the piperazine diamine series (ROMK and hERG IC50values determined in86Rb+efflux and35S-MK499 binding assays, respectively, unless otherwise indicated; EP, electrophysiology).ACS Med Chem Lett.2016 May 12;7(7):697-701. |
Synthesis of stereoisomers of10.ACS Med Chem Lett.2016 May 12;7(7):697-701. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
