Record Information |
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Version | 5.0 |
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Status | Detected but not Quantified |
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Creation Date | 2021-09-11 14:22:55 UTC |
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Update Date | 2021-09-26 23:09:19 UTC |
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HMDB ID | HMDB0254901 |
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Secondary Accession Numbers | None |
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Metabolite Identification |
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Common Name | Motesanib |
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Description | Motesanib, also known as AMG 706, belongs to the class of organic compounds known as indolines. Indolines are compounds containing an indole moiety, which consists of pyrrolidine ring fused to benzene to form 2,3-dihydroindole. It is an orally administered small molecule belonging to angiokinase inhibitor class which acts as an antagonist of VEGF receptors, platelet-derived growth factor receptors, and stem cell factor receptors. Motesanib is a very strong basic compound (based on its pKa). However a later and more detailed Phase III trial failed to show any benefit for the treatment of NSCLC. After clinical trials in thyroid cancer, non-small cell lung cancer, gastrointestinal stromal cancer, colorectal cancer, and breast cancer, the drug was not found to show sufficient efficacy for further development, and development was abandoned by Takeda. Two phase II clinical trials for thyroid cancer showed promising results. Motesanib was originally investigated for effectiveness against advanced nonsquamous non-small-cell lung cancer (NSCLC), with Phase II trials indicating an effectiveness comparable to bevacizumab when they were both used in combination with paclitaxel/carboplatin. Phase II testing against persistent or recurrent ovarian, fallopian tube and primary peritoneal carcinomas was also unsuccessful. A second Phase III trial was started in 2012, which focused on patients from Asian backgrounds (performed on the bases of subgroup analysis) however this also failed to meet its primary endpoint. The drug has undergone a Phase II evaluation as first-line therapy for breast cancer however this study found no evidence to support further investigation. This compound has been identified in human blood as reported by (PMID: 31557052 ). Motesanib is not a naturally occurring metabolite and is only found in those individuals exposed to this compound or its derivatives. Technically Motesanib is part of the human exposome. The exposome can be defined as the collection of all the exposures of an individual in a lifetime and how those exposures relate to health. An individual's exposure begins before birth and includes insults from environmental and occupational sources. |
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Structure | CC1(C)CNC2=C1C=CC(=C2)N=C(O)C1=C(NCC2=CC=NC=C2)N=CC=C1 InChI=1S/C22H23N5O/c1-22(2)14-26-19-12-16(5-6-18(19)22)27-21(28)17-4-3-9-24-20(17)25-13-15-7-10-23-11-8-15/h3-12,26H,13-14H2,1-2H3,(H,24,25)(H,27,28) |
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Synonyms | Value | Source |
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N-(2,3-Dihydro-3,3-dimethyl-1H-indol-6-yl)-2-((4-pyridinylmethyl)amino)-3-pyridinecarboxamide | ChEBI | AMG 706 | Kegg | Motesanib diphosphate | MeSH | AMG-706 | MeSH | Imetelstat | MeSH |
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Chemical Formula | C22H23N5O |
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Average Molecular Weight | 373.4509 |
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Monoisotopic Molecular Weight | 373.190260383 |
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IUPAC Name | N-(3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-2-[(pyridin-4-ylmethyl)amino]pyridine-3-carboximidic acid |
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Traditional Name | motesanib |
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CAS Registry Number | Not Available |
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SMILES | CC1(C)CNC2=C1C=CC(=C2)N=C(O)C1=C(NCC2=CC=NC=C2)N=CC=C1 |
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InChI Identifier | InChI=1S/C22H23N5O/c1-22(2)14-26-19-12-16(5-6-18(19)22)27-21(28)17-4-3-9-24-20(17)25-13-15-7-10-23-11-8-15/h3-12,26H,13-14H2,1-2H3,(H,24,25)(H,27,28) |
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InChI Key | RAHBGWKEPAQNFF-UHFFFAOYSA-N |
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Chemical Taxonomy |
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Description | Belongs to the class of organic compounds known as indolines. Indolines are compounds containing an indole moiety, which consists of pyrrolidine ring fused to benzene to form 2,3-dihydroindole. |
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Kingdom | Organic compounds |
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Super Class | Organoheterocyclic compounds |
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Class | Indoles and derivatives |
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Sub Class | Indolines |
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Direct Parent | Indolines |
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Alternative Parents | |
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Substituents | - Dihydroindole
- Nicotinamide
- Pyridinecarboxamide
- Pyridine carboxylic acid or derivatives
- Aminopyridine
- Secondary aliphatic/aromatic amine
- Aralkylamine
- Imidolactam
- Benzenoid
- Pyridine
- Heteroaromatic compound
- Vinylogous amide
- Secondary carboxylic acid amide
- Carboxamide group
- Amino acid or derivatives
- Azacycle
- Secondary amine
- Carboxylic acid derivative
- Organonitrogen compound
- Organic oxygen compound
- Organic nitrogen compound
- Hydrocarbon derivative
- Amine
- Organooxygen compound
- Organopnictogen compound
- Organic oxide
- Aromatic heteropolycyclic compound
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Molecular Framework | Aromatic heteropolycyclic compounds |
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External Descriptors | |
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Ontology |
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Physiological effect | Not Available |
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Disposition | |
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Process | Not Available |
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Role | Not Available |
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Physical Properties |
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State | Not Available |
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Experimental Molecular Properties | Property | Value | Reference |
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Melting Point | Not Available | Not Available | Boiling Point | Not Available | Not Available | Water Solubility | Not Available | Not Available | LogP | Not Available | Not Available |
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Experimental Chromatographic Properties | Not Available |
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Predicted Molecular Properties | |
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Predicted Chromatographic Properties | Predicted Collision Cross SectionsPredicted Kovats Retention IndicesUnderivatizedDerivatizedDerivative Name / Structure | SMILES | Kovats RI Value | Column Type | Reference |
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Motesanib,2TMS,isomer #1 | CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3NCC3=CC=NC=C3)=CC=C21 | 3302.2 | Semi standard non polar | 33892256 | Motesanib,2TMS,isomer #1 | CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3NCC3=CC=NC=C3)=CC=C21 | 3115.6 | Standard non polar | 33892256 | Motesanib,2TMS,isomer #1 | CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3NCC3=CC=NC=C3)=CC=C21 | 4057.6 | Standard polar | 33892256 | Motesanib,2TMS,isomer #2 | CC1(C)CNC2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C21 | 3251.0 | Semi standard non polar | 33892256 | Motesanib,2TMS,isomer #2 | CC1(C)CNC2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C21 | 3071.0 | Standard non polar | 33892256 | Motesanib,2TMS,isomer #2 | CC1(C)CNC2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C21 | 4156.7 | Standard polar | 33892256 | Motesanib,2TMS,isomer #3 | CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C21 | 3171.3 | Semi standard non polar | 33892256 | Motesanib,2TMS,isomer #3 | CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C21 | 3173.0 | Standard non polar | 33892256 | Motesanib,2TMS,isomer #3 | CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C21 | 3890.1 | Standard polar | 33892256 | Motesanib,3TMS,isomer #1 | CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C21 | 3183.5 | Semi standard non polar | 33892256 | Motesanib,3TMS,isomer #1 | CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C21 | 3013.1 | Standard non polar | 33892256 | Motesanib,3TMS,isomer #1 | CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C21 | 3806.6 | Standard polar | 33892256 | Motesanib,2TBDMS,isomer #1 | CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3NCC3=CC=NC=C3)=CC=C21 | 3665.7 | Semi standard non polar | 33892256 | Motesanib,2TBDMS,isomer #1 | CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3NCC3=CC=NC=C3)=CC=C21 | 3523.0 | Standard non polar | 33892256 | Motesanib,2TBDMS,isomer #1 | CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3NCC3=CC=NC=C3)=CC=C21 | 4240.0 | Standard polar | 33892256 | Motesanib,2TBDMS,isomer #2 | CC1(C)CNC2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C21 | 3595.2 | Semi standard non polar | 33892256 | Motesanib,2TBDMS,isomer #2 | CC1(C)CNC2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C21 | 3499.4 | Standard non polar | 33892256 | Motesanib,2TBDMS,isomer #2 | CC1(C)CNC2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C21 | 4300.2 | Standard polar | 33892256 | Motesanib,2TBDMS,isomer #3 | CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C21 | 3531.5 | Semi standard non polar | 33892256 | Motesanib,2TBDMS,isomer #3 | CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C21 | 3570.4 | Standard non polar | 33892256 | Motesanib,2TBDMS,isomer #3 | CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C21 | 4091.0 | Standard polar | 33892256 | Motesanib,3TBDMS,isomer #1 | CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C21 | 3654.5 | Semi standard non polar | 33892256 | Motesanib,3TBDMS,isomer #1 | CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C21 | 3608.6 | Standard non polar | 33892256 | Motesanib,3TBDMS,isomer #1 | CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C21 | 4041.5 | Standard polar | 33892256 |
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| GC-MS SpectraSpectrum Type | Description | Splash Key | Deposition Date | Source | View |
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Predicted GC-MS | Predicted GC-MS Spectrum - Motesanib GC-MS (Non-derivatized) - 70eV, Positive | splash10-03di-2946000000-1ef0ca696060501f3f2a | 2021-09-24 | Wishart Lab | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - Motesanib GC-MS (Non-derivatized) - 70eV, Positive | Not Available | 2021-10-12 | Wishart Lab | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - Motesanib GC-MS (TMS_1_1) - 70eV, Positive | Not Available | 2021-11-04 | Wishart Lab | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - Motesanib GC-MS (TMS_1_2) - 70eV, Positive | Not Available | 2021-11-04 | Wishart Lab | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - Motesanib GC-MS (TMS_1_3) - 70eV, Positive | Not Available | 2021-11-04 | Wishart Lab | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - Motesanib GC-MS (TBDMS_1_1) - 70eV, Positive | Not Available | 2021-11-04 | Wishart Lab | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - Motesanib GC-MS (TBDMS_1_2) - 70eV, Positive | Not Available | 2021-11-04 | Wishart Lab | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - Motesanib GC-MS (TBDMS_1_3) - 70eV, Positive | Not Available | 2021-11-04 | Wishart Lab | View Spectrum |
MS/MS SpectraSpectrum Type | Description | Splash Key | Deposition Date | Source | View |
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Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - Motesanib 10V, Positive-QTOF | splash10-00di-0319000000-bbbc4c281a4482625f07 | 2017-07-26 | Wishart Lab | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - Motesanib 20V, Positive-QTOF | splash10-03di-0964000000-bba5a667744363751e61 | 2017-07-26 | Wishart Lab | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - Motesanib 40V, Positive-QTOF | splash10-001i-2910000000-f5a86b88d6e9b2275cf6 | 2017-07-26 | Wishart Lab | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - Motesanib 10V, Negative-QTOF | splash10-00di-0209000000-498dc66e76f2594d4be2 | 2017-07-26 | Wishart Lab | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - Motesanib 20V, Negative-QTOF | splash10-00ai-3928000000-a7604c4b45cc3a77a64d | 2017-07-26 | Wishart Lab | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - Motesanib 40V, Negative-QTOF | splash10-0036-9800000000-fd642651adf843ecf1a3 | 2017-07-26 | Wishart Lab | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - Motesanib 10V, Positive-QTOF | splash10-00dl-5009000000-dcd41693e3867ddd92ff | 2021-10-12 | Wishart Lab | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - Motesanib 20V, Positive-QTOF | splash10-0006-9001000000-798e475acde23e9e6586 | 2021-10-12 | Wishart Lab | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - Motesanib 40V, Positive-QTOF | splash10-0006-9110000000-125dab2f1311665d77c8 | 2021-10-12 | Wishart Lab | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - Motesanib 10V, Negative-QTOF | splash10-00di-0009000000-0c83a5fa76cb48159b4a | 2021-10-12 | Wishart Lab | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - Motesanib 20V, Negative-QTOF | splash10-00di-3229000000-ec7012978521c4c7e352 | 2021-10-12 | Wishart Lab | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - Motesanib 40V, Negative-QTOF | splash10-0a6r-5942000000-28ac66c588ffbe0d70f2 | 2021-10-12 | Wishart Lab | View Spectrum |
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