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ATM-3507 is a potent tropomyosin inhibitor with IC 50 s from 3.83-6.84 μM in human melanoma cell lines.
In Vitro
The cell lines differ in their relative expression of Tpm3.1 as well as in the expression of other isoforms. After determing the IC 50 concentrations for TR100 and ATM-3507 (CHLA-20: 4.99±0.45 μM, CHP-134: 3.83±0.67 μM, CHLA-90: 6.84±2.37 μM, SK-N-BE(2): 5.00±0.42 μM) in each of the neuroblastoma cell lines, combinations of tropomyosin inhibitors plus Vincristine are tested at levels of each drug alone that kill less than 50% of the neuroblastoma cells. The combinations of both tropomyosin inhibitors plus Vincristine are completely cytotoxic in CHLA-20 cells. All 4 cell lines show some degree of synergy as determined by the Chou–Talalay method. The effect is not limited to the vinca alkaloids as a similar combination efficacy using paclitaxel plus TR100 or ATM-3507. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
The maximal tolerance dose (MTD) for TR100 and ATM-3507 is 60 and 150 mg/kg, respectively. It is found that a significant inhibition of tumor growth and prolongation of animal survival using either combination compared with each monotherapy. The median survival of mice increased from 18 days for mice treated with ATM-3507 to more than 49 days for mice treated with the combination. It is also found that twice weekly intravenous administration of ATM-3507 also show combination efficacy. The impact of each treatment or the combination on body weight is minimal. Drug levels are measured following the intravenous administration of ATM-3507 at 30 mg/kg in Balb/c mice (n=3 per time point). The mean half-life of ATM-3507 is 5.01 hrs for the terminal elimination phase. The mean AUC 0-t in the plasma is 14,548 ng/h/mL. The C max of ATM-3507 is 5,758 ng/mL and the the t 1/2 is 5.01 h. The observed plasma clearance and volume of distribution at steady state of ATM-3507 is 33.8 mL/min/kg and 7.23 L/kg, respectively . MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Form:Solid
IC50& Target:IC50: 3.83-6.84 μM (tropomyosin, in human melanoma celllines)
| Canonical Smiles | CC1=C(N(C2=C1C=C(C=C2)OC3=CC=CC(=C3)C(=O)N4CCN(CC4)CCC5=CC=C(C=C5)F)CCCN6CCN(CC6)C)C |
|---|---|
| IUPAC Name | [3-[2,3-dimethyl-1-[3-(4-methylpiperazin-1-yl)propyl]indol-5-yl]oxyphenyl]-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]methanone |
| InChIKey | FNEHSJQRIWHZKS-UHFFFAOYSA-N |
| INCHI | 1S/C37H46FN5O2/c1-28-29(2)43(16-5-15-40-20-18-39(3)19-21-40)36-13-12-34(27-35(28)36)45-33-7-4-6-31(26-33)37(44)42-24-22-41(23-25-42)17-14-30-8-10-32(38)11-9-30/h4,6-13,26-27H,5,14-25H2,1-3H3 |
| Isomeric SMILES | CC1=C(N(C2=C1C=C(C=C2)OC3=CC=CC(=C3)C(=O)N4CCN(CC4)CCC5=CC=C(C=C5)F)CCCN6CCN(CC6)C)C |
| Alternate CAS | 1861449-70-8 |
| PubChem CID | 118666864 |
| Molecular Weight | 611.79 |
Comprehensive hazard, handling, storage, and regulatory compliance document.
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View spec sheet →Taxonomy Tree
| Kingdom | Organic compounds |
|---|---|
| Superclass | Organoheterocyclic compounds |
| Class | Indoles and derivatives |
| Subclass | Indoles |
| Intermediate Tree Nodes | 3-alkylindoles |
| Direct Parent | 3-methylindoles |
| Alternative Parents | N-alkylindoles Phenethylamines Benzamides Phenol ethers Benzoyl derivatives N-methylpiperazines Fluorobenzenes Substituted pyrroles N-acyl amines Tertiary carboxylic acid amides Heteroaromatic compounds Trialkylamines Amino acids and derivatives Ethers Azacyclic compounds Organopnictogen compounds Organofluorides Organic oxides Hydrocarbon derivatives |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | 3-methylindole - N-alkylindole - Phenethylamine - Benzoic acid or derivatives - Benzamide - Phenol ether - Benzoyl - N-alkylpiperazine - N-methylpiperazine - Halobenzene - Fluorobenzene - Benzenoid - Substituted pyrrole - Piperazine - N-acyl-amine - 1,4-diazinane - Monocyclic benzene moiety - Heteroaromatic compound - Tertiary carboxylic acid amide - Tertiary aliphatic amine - Tertiary amine - Carboxamide group - Amino acid or derivatives - Azacycle - Ether - Carboxylic acid derivative - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Organofluoride - Organohalogen compound - Amine - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as 3-methylindoles. These are aromatic heterocyclic compounds that contain an indole moiety substituted at the 3-position with a methyl group. |
| External Descriptors | Not available |
| Solubility | DMSO : 33.33 mg/mL (54.48 mM; Need ultrasonic) |
|---|---|
| Molecular Weight | 611.800 g/mol |
| XLogP3 | 5.800 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 10 |
| Exact Mass | 611.364 Da |
| Monoisotopic Mass | 611.364 Da |
| Topological Polar Surface Area | 44.200 Ų |
| Heavy Atom Count | 45 |
| Formal Charge | 0 |
| Complexity | 916.000 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| The total count of all stereochemical bonds | 0 |
| Covalently-Bonded Unit Count | 1 |