| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| Other Sizes |
| Targets |
MA-2029 targets the motilin receptor. It acts as a selective, competitive antagonist with an IC50 of 4.9 nM. The compound has a pA2 value of 9.17 and shows high selectivity over a range of other receptors and ion channels.
|
|---|---|
| ln Vitro |
The contraction of isolated rabbit duodenum longitudinal muscle strips elicited by motilin is competitively inhibited by MA-2029 (1 to 30 nM), showing a pA2 value of 9.17˱0.01. Even at a dosage of 1 μM MA-2029, contractile responses to substance P and acetylcholine remained unaltered. Rabbit colonic smooth muscle tissue and HEK 293 cell membrane homogenates expressing human motilin receptors are subject to concentration-dependent inhibition of [125I]motilin binding by MA-2029. pKi for MA-2029 is 8.38 in HEK 293 cells and 8.58±0.04 in rabbit colon homogenate [1].
MA-2029 potently inhibits the motilin receptor with an IC50 of 4.9 nM and displaces [125I]motilin with an IC50 of 2.74 nM. It shows high selectivity over other receptors and ion channels. The compound inhibits motilin-induced intestinal contractions and visceral pain in rabbits. |
| ln Vivo |
The number of abdominal muscular contractions elicited under the same conditions is dosage-dependently inhibited by MA-2029 (0.3-3 mg/kg; oral), with a dose of 3 mg/kg causing a considerable suppression [1]. The oral MA-2029 (10 mg/kg) therapy showed a t1/2 of two hours [1]. When 3 mg/kg or more is administered, significant inhibition happens 30 minutes later, and when 10 mg/kg or more is administered, it happens 4 hours later (MA-2029). As a result, the inhibitory action starts to take effect 30 minutes after administering 10 mg/kg or greater, or at least 4 hours later [ 1].
In vivo, MA-2029 is orally active and inhibits motilin-induced intestinal contractions and visceral pain in rabbits. The compound has potential applications in gastrointestinal disorders associated with disturbed gastrointestinal motility. Its oral activity makes it suitable for therapeutic development. |
| Enzyme Assay |
In vitro receptor binding assays measure the displacement of [125I]motilin from motilin receptors expressed in cell membranes. MA-2029 is incubated with membrane preparations and the radiolabeled ligand, and the IC50 is determined. Functional assays measure the inhibition of motilin-induced contractions in smooth muscle preparations.
|
| Cell Assay |
In vitro cellular assays evaluate the antagonist activity of MA-2029 on cells expressing the motilin receptor. Cells are treated with motilin in the presence or absence of MA-2029, and receptor activation is measured by calcium mobilization or other second messenger assays. The IC50 for antagonism is determined from dose-response curves.
|
| Animal Protocol |
Animal/Disease Models: Male Japanese white rabbit (approximately 2-3 kg) [1]
Doses: 0.3, 1, 3 mg/kg Route of Administration: Oral Experimental Results:Dose-dependent inhibition of the number of abdominal muscle contractions induced under the same conditions. 3 mg/kg caused significant inhibition. Animal/Disease Models: Male Japanese white rabbit (approximately 2-3 kg) [1] Doses: 10 mg/kg Route of Administration: Oral (pharmacokinetic/PK/PK analysis) Experimental Results: t1/2 is 2 hrs (hrs (hours)). In vivo animal experiments are conducted in rabbit models to study the effects of MA-2029 on gastrointestinal motility. The compound is administered orally or intravenously. Motilin-induced intestinal contractions and visceral pain are measured. The compound's effects on gastrointestinal motility are assessed. |
| ADME/Pharmacokinetics |
MA-2029 has a CAS number of 287206-61-5. It is an orally active, competitive motilin receptor antagonist. The compound is also known as MA 2029 and MA2029. Its chemical name is 4-Fluoro-N-methyl-L-phenylalanyl-N-methyl-L-valyl-3-(1,1-dimethylethyl)-N-ethyl-L-tyrosinamide.
|
| Toxicity/Toxicokinetics |
The toxicity profile of MA-2029 is related to its mechanism as a motilin receptor antagonist. The compound shows high selectivity over other receptors and ion channels, suggesting a favorable safety profile. Standard toxicological studies would be required for clinical development.
|
| References | |
| Additional Infomation |
See also: MA-2029 (notes moved to).
MA-2029 is a research tool for studying the role of motilin in gastrointestinal motility. It has potential therapeutic applications in gastrointestinal disorders associated with disturbed motility. The compound is also known as a selective motilin receptor antagonist. It has been used to study the physiological and pathological roles of motilin signaling. |
| Molecular Formula |
C31H46CLFN4O4
|
|---|---|
| Molecular Weight |
593.17275094986
|
| Exact Mass |
556.342
|
| CAS # |
287206-61-5
|
| PubChem CID |
10144175
|
| Appearance |
White to off-white solid powder
|
| LogP |
5.1
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
13
|
| Heavy Atom Count |
40
|
| Complexity |
825
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
Cl.CCNC([C@H](CC1C=CC(O)=C(C(C)(C)C)C=1)NC([C@@H](N(C([C@H](CC1=CC=C(F)C=C1)NC)=O)C)C(C)C)=O)=O
|
| InChi Key |
KSDWAJPUTRBIRR-KLJDGLGGSA-N
|
| InChi Code |
InChI=1S/C31H45FN4O4/c1-9-34-28(38)24(18-21-12-15-26(37)23(16-21)31(4,5)6)35-29(39)27(19(2)3)36(8)30(40)25(33-7)17-20-10-13-22(32)14-11-20/h10-16,19,24-25,27,33,37H,9,17-18H2,1-8H3,(H,34,38)(H,35,39)/t24-,25-,27-/m0/s1
|
| Chemical Name |
(2S)-N-[(2S)-3-(3-tert-butyl-4-hydroxyphenyl)-1-(ethylamino)-1-oxopropan-2-yl]-2-[[(2S)-3-(4-fluorophenyl)-2-(methylamino)propanoyl]-methylamino]-3-methylbutanamide
|
| Synonyms |
MA2029; MA 2029; MA-2029
|
| 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) |
DMSO: ~100 mg/mL (~179.6 mM; with ultrasonication)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.49 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: ≥ 2.5 mg/mL (4.49 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (4.49 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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6859 mL | 8.4293 mL | 16.8586 mL | |
| 5 mM | 0.3372 mL | 1.6859 mL | 3.3717 mL | |
| 10 mM | 0.1686 mL | 0.8429 mL | 1.6859 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
