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| 25mg |
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Purity: ≥98%
ML-18 (the S-enantiomer, the enantiomer is EMY-98), a nonpeptide analogs of PD176252, is a BRS-3 (Bombesin receptor subtype 3) antagonist with an IC50 of 4.8 μM. ML-18 and EMY-98, with IC50 values of 4.8 and >100μM, respectively, inhibited specific (125)I-BA1 (DTyr-Gln-Trp-Ala-Val-βAla-His-Phe-Nle-NH2)BB(6-14) binding to NCI-H1299 lung cancer cells that were stably transfected with BRS-3. On the other hand, ML-18 exhibited a lower affinity for binding to the GRPR and NMBR, with IC50 values exceeding 100μM and 16μM, respectively. With lung cancer cells loaded with FURA2-AM, ML-18 (16μM) but not its enantiomer EMY-98 inhibited 10nM BA1's capacity to elevate cytosolic Ca(2+) in a reversible manner. Lung cancer cells' ability to become tyrosine phosphorylated on EGFR and ERK in response to 100nM BA1 was inhibited by ML-18 (16μM), but not by EMY-98. ML-18 but not EMY-98 inhibited the proliferation of lung cancer cells. The findings suggest that ML-18 is a nonpeptide antagonist of BRS-3 that can be used as a model to increase potency and selectivity. A G protein coupled receptor (GPCR) for the bombesin (BB)-family of peptides is known as the bombesin receptor subtype (BRS)-3. As an orphan GPCR, BRS-3's physiological function is poorly understood because there aren't any particular agonists or antagonists. While PD176252 is a nonpeptide antagonist for the gastrin releasing peptide (GRP) R and NMBR but not BRS-3, PD168368 is a nonpeptide antagonist for the neuromedin B (NMB) receptor (R).
| Targets |
BRS-3 ( IC50 = 4.8 μM )
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| ln Vitro |
ML-18 blocks specific 125I-BA1 (DTyr-Gln-Trp-Ala-Val-βAla-His-Phe-Nle-NH2)BB6-14 binding to NCI-H1299 lung cancer cells that have been stably transfected with BRS-3 with IC50 values of 4.8 μM. ML-18 exhibits a reduced affinity for binding the GRPR and NMBR, with IC50 values exceeding 100 μM and 16 μM, respectively. ML-18 at 16 μM reversibly prevents 10 nM BA1 from increasing cytosolic Ca2+ in lung cancer cells that have been loaded with FURA2-AM. ML-18 at 16 μM prevents 100 nM BA1 from causing EGFR and ERK tyrosine phosphorylation in lung cancer cells. It prevents lung cancer cells from proliferating[1].
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| Enzyme Assay |
The cells are cultured in SIT buffer supplemented with varying concentrations of unlabelled competitor (ML-18), 0.25% bovine serum albumin, 250 μg/mL bacitracin, and 1253I-BA1 (100,000 cpm). Following a 30-minute incubation period at 37°C, free 1253I-BA1 is eliminated by three rounds of buffer washing, and the cells containing bound 1253I-BA1 are dissolved in 0.2 N NaOH and counted using a gamma counter. For every competitor without a label, the IC50 is computed[1].
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| Cell Assay |
The MTT assay is used to determine cell viability. After transfecting NCI-H727 or NCI-H1299 cells with BRS-3, ML-18 (0, 4.8, 16, 48 μM) or gefitinib is added. 15 μL of 0.1% MTT solution was added after two days. 150 μL of DMSO is added after 4 hours. The optical density at 570 nm is calculated after 16 hours[1].
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| References |
| Molecular Formula |
C32H35N5O5
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| Molecular Weight |
569.66
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| Exact Mass |
569.263
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| Elemental Analysis |
C, 67.47; H, 6.19; N, 12.29; O, 14.04
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| CAS # |
1422269-30-4
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| Related CAS # |
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| PubChem CID |
91827363
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| Appearance |
White to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
803.5±75.0 °C at 760 mmHg
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| Flash Point |
439.7±37.1 °C
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| Vapour Pressure |
0.0±3.0 mmHg at 25°C
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| Index of Refraction |
1.652
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| LogP |
8.03
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
42
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| Complexity |
906
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C([C@]([H])(C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12)N([H])C(N([H])C1C([H])=C([H])C(=C([H])C=1[H])[N+](=O)[O-])=O)N([H])C([H])([H])C1(C2C([H])=C([H])C(=C([H])C=2[H])OC([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H]
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| InChi Key |
JOKVJNCYOSFDGC-LJAQVGFWSA-N
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| InChi Code |
InChI=1S/C32H35N5O5/c1-42-26-15-9-23(10-16-26)32(17-5-2-6-18-32)21-34-30(38)29(19-22-20-33-28-8-4-3-7-27(22)28)36-31(39)35-24-11-13-25(14-12-24)37(40)41/h3-4,7-16,20,29,33H,2,5-6,17-19,21H2,1H3,(H,34,38)(H2,35,36,39)/t29-/m0/s1
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| Chemical Name |
(2S)-3-(1H-indol-3-yl)-N-[[1-(4-methoxyphenyl)cyclohexyl]methyl]-2-[(4-nitrophenyl)carbamoylamino]propanamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.39 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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 2: ≥ 2.5 mg/mL (4.39 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 25.0 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 | 1.7554 mL | 8.7772 mL | 17.5543 mL | |
| 5 mM | 0.3511 mL | 1.7554 mL | 3.5109 mL | |
| 10 mM | 0.1755 mL | 0.8777 mL | 1.7554 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.
Receptor binding. |
Cytosolic Ca2+. BRS-3 transfected NCI-H1299 cells were loaded with Fura-2AM and the cytosolic Ca2+determined for 4 min after the addition of (A) 10 nM BA1, (B) 16 μM EMY-98 followed by 10 nM BA1, (C) 16 μM ML-18 followed by 10 nM BA1, (D) NCI-H727 cells are treated with 16 μM ML-18 followed by 10 nM BA1, 0.1 μM BA1 and 1 μM BA1.
MTT assay.Peptides.2015 Feb;64:55-61. |
Western blot.
Cytosolic Ca2+. NCI-H727 cells were loaded with Fura-2AM and the cytosolic Ca2+determined for 4 min after the addition of (A) 10 nM MK 5046 (MK), (B) 16 μM ML-18 followed by 10 nM MK, (C) 16 μM EMY-98 followed by 10 nM MK and (D) 1 μM Bantag (Ban) by 10 nM MK.Peptides.2015 Feb;64:55-61. |
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