tonabersat: potential antimigraine agent; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 6918324 |
| CHEMBL ID | 318191 |
| SCHEMBL ID | 5917016 |
| MeSH ID | M0304120 |
| Synonym |
|---|
| CHEMBL318191 |
| HY-15204 |
| tonabersat |
| sb-220453 |
| usl-260 |
| n-[(3s,4s)-6-acetyl-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]-3-chloro-4-fluorobenzamide |
| sb 220453 |
| 6-acetyl-4-(3-chloro-4-fluorobenzoylamino)-3,4-dihydro-2,2-dimethyl-2h-benzo(b)pyran-3-ol |
| 175013-84-0 |
| unii-2xd9773zmn |
| tonabersat [inn:ban] |
| n-((3s,4s)-6-acetyl-3-hydroxy-2,2-dimethylchroman-4-yl)-3-chloro-4-fluorobenzamide |
| 2xd9773zmn , |
| 2h-benzo(b)pyran-3-ol, 6-acetyl-4-(3-chloro-4-fluorobenzoylamino)-3,4-dihydro-2,2-dimethyl- |
| AKOS015994581 |
| CS-0676 |
| tonabersat [inn] |
| tonabersat [who-dd] |
| SCHEMBL5917016 |
| ES-0039 |
| (3s,4s)-6-acetyl-4-(3-chloro-4-fluorobenzamido)-3,4-dihydro-2,2-dimethyl-3-hydroxy-2h-1-benzopyran |
| XLIIRNOPGJTBJD-ROUUACIJSA-N |
| n-[(3s,4s)-6-acetyl-3-hydroxy-2,2-dimethyl-3,4-dihydro-2h-1-benzopyran-4-yl]-3-chloro-4-fluorobenzamide |
| DTXSID40169923 |
| tonabersat, >=98% (hplc) |
| NCGC00379030-01 |
| DB06578 |
| benzamide, n-[(3s,4s)-6-acetyl-3,4-dihydro-3-hydroxy-2,2-dimethyl-2h-1-benzopyran-4-yl]-3-chloro-4-fluoro- |
| Q27255763 |
Tonabersat is a novel putative migraine prophylactic agent with an unique stereospecific binding site in the brain. It blocks the cortical spreading depression proposed to be associated with migraine attacks.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Tonabersat is a novel putative migraine prophylactic agent with an unique stereospecific binding site in the brain. " | ( Randomized, double-blind, placebo-controlled, proof-of-concept study of the cortical spreading depression inhibiting agent tonabersat in migraine prophylaxis. Csanyi, A; Ferrari, MD; Goadsby, PJ; Mills, JG; Olesen, J, 2009) | 2 |
| "Tonabersat is a novel benzopyran derivative that blocks the cortical spreading depression proposed to be associated with migraine attacks. " | ( Tonabersat, a gap-junction modulator: efficacy and safety in two randomized, placebo-controlled, dose-ranging studies of acute migraine. Diener, HC; Elkind, AH; Göbel, H; Howard, RA; Klapper, JA; Schoenen, J; Silberstein, SD, 2009) | 3.24 |
| "Tonabersat is a unique compound with demonstrated activity as a gap-junction inhibitor in animal studies." | ( Tonabersat, a novel gap-junction modulator for the prevention of migraine. Silberstein, SD, 2009) | 2.52 |
| Excerpt | Reference | Relevance |
|---|---|---|
| "Tonabersat has been shown, in animal models, to inhibit experimentally induced cortical spreading depression, the likely underlying mechanism for migraine aura, and cerebrovascular responses to trigeminal nerve stimulation." | ( Randomized, double-blind, placebo-controlled, proof-of-concept study of the cortical spreading depression inhibiting agent tonabersat in migraine prophylaxis. Csanyi, A; Ferrari, MD; Goadsby, PJ; Mills, JG; Olesen, J, 2009) | 1.28 |
Tonabersat treatment reduced inflammation in the retina in parallel with preservation of retinal photoreceptor function when assessed up to 3 months post light damage in the dry AMD model. Pretreatment with tonabers at inhibited gap junction communication between neurons and satellite glia.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Tonabersat treatment reduced inflammation in the retina in parallel with preservation of retinal photoreceptor function when assessed up to 3 months post light damage in the dry AMD model." | ( Connexin Hemichannel Block Using Orally Delivered Tonabersat Improves Outcomes in Animal Models of Retinal Disease. Acosta, ML; Green, CR; Mat Nor, MN; Rupenthal, ID, 2020) | 1.53 |
| "Pretreatment with tonabersat inhibited gap junction communication between neurons and satellite glia and blocked the increase in connexin 26 and active p38 levels in response to injection of both tumor necrosis factor-alpha (V2) and capsaicin (V1)." | ( Tonabersat inhibits trigeminal ganglion neuronal-satellite glial cell signaling. Damodaram, S; Durham, PL; Freeman, SE; Garrett, FG; Thalakoti, S, 2009) | 2.12 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " Serious adverse events were uncommon, and no patient withdrew from either study because of adverse events." | ( Tonabersat, a gap-junction modulator: efficacy and safety in two randomized, placebo-controlled, dose-ranging studies of acute migraine. Diener, HC; Elkind, AH; Göbel, H; Howard, RA; Klapper, JA; Schoenen, J; Silberstein, SD, 2009) | 1.8 |
The orally bioavailable modulators of gap junctions meclofenamate and tonabersat break this paracrine loop. We provide proof-of-principle that these drugs could be used to treat established brain metastasis.
| Protein | Taxonomy | Measurement | Average (µ) | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| cytochrome P450 family 3 subfamily A polypeptide 4 | Homo sapiens (human) | Potency | 26.8370 | 0.0123 | 7.9835 | 43.2770 | AID1645841 |
| G | Vesicular stomatitis virus | Potency | 2.6837 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| cytochrome P450 2D6 | Homo sapiens (human) | Potency | 0.6741 | 0.0010 | 8.3798 | 61.1304 | AID1645840 |
| Interferon beta | Homo sapiens (human) | Potency | 2.6837 | 0.0033 | 9.1582 | 39.8107 | AID1645842 |
| HLA class I histocompatibility antigen, B alpha chain | Homo sapiens (human) | Potency | 2.6837 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| Inositol hexakisphosphate kinase 1 | Homo sapiens (human) | Potency | 2.6837 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| cytochrome P450 2C9, partial | Homo sapiens (human) | Potency | 2.6837 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1346987 | P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1296008 | Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening | 2020 | SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1 | Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening. |
| AID1346986 | P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1347160 | Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID1347159 | Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID130833 | In vivo percent increase in seizure threshold in mouse MEST model 1 hour following 10 mg/kg p.o. | 1999 | Bioorganic & medicinal chemistry letters, Jan-18, Volume: 9, Issue:2 | Identification of (-)-cis-6-acetyl-4S-(3-chloro-4-fluoro-benzoylamino)- 3,4-dihydro-2,2-dimethyl-2H-benzo[b]pyran-3S-ol as a potential antimigraine agent. |
| AID184099 | In vivo percent increase in seizure threshold in rat MEST model at the dose of 3 mg/kg p.o. recorded 1 hr post dose | 1999 | Bioorganic & medicinal chemistry letters, Jan-18, Volume: 9, Issue:2 | Identification of (-)-cis-6-acetyl-4S-(3-chloro-4-fluoro-benzoylamino)- 3,4-dihydro-2,2-dimethyl-2H-benzo[b]pyran-3S-ol as a potential antimigraine agent. |
| AID184094 | In vivo percent increase in seizure threshold in mouse MEST model 4 hours following 10 mg/kg p.o. | 1999 | Bioorganic & medicinal chemistry letters, Jan-18, Volume: 9, Issue:2 | Identification of (-)-cis-6-acetyl-4S-(3-chloro-4-fluoro-benzoylamino)- 3,4-dihydro-2,2-dimethyl-2H-benzo[b]pyran-3S-ol as a potential antimigraine agent. |
| AID184102 | In vivo percent increase in seizure threshold in rat MEST model at the dose of 3 mg/kg p.o. recorded 6 hr post dose | 1999 | Bioorganic & medicinal chemistry letters, Jan-18, Volume: 9, Issue:2 | Identification of (-)-cis-6-acetyl-4S-(3-chloro-4-fluoro-benzoylamino)- 3,4-dihydro-2,2-dimethyl-2H-benzo[b]pyran-3S-ol as a potential antimigraine agent. |
| AID184097 | In vivo percent increase in seizure threshold in rat MEST model at the dose of 3 mg/kg p.o. recorded 0.25 hr post dose | 1999 | Bioorganic & medicinal chemistry letters, Jan-18, Volume: 9, Issue:2 | Identification of (-)-cis-6-acetyl-4S-(3-chloro-4-fluoro-benzoylamino)- 3,4-dihydro-2,2-dimethyl-2H-benzo[b]pyran-3S-ol as a potential antimigraine agent. |
| AID184098 | In vivo percent increase in seizure threshold in rat MEST model at the dose of 3 mg/kg p.o. recorded 0.5 hr post dose | 1999 | Bioorganic & medicinal chemistry letters, Jan-18, Volume: 9, Issue:2 | Identification of (-)-cis-6-acetyl-4S-(3-chloro-4-fluoro-benzoylamino)- 3,4-dihydro-2,2-dimethyl-2H-benzo[b]pyran-3S-ol as a potential antimigraine agent. |
| AID184100 | In vivo percent increase in seizure threshold in rat MEST model at the dose of 3 mg/kg p.o. recorded 2 hr post dose | 1999 | Bioorganic & medicinal chemistry letters, Jan-18, Volume: 9, Issue:2 | Identification of (-)-cis-6-acetyl-4S-(3-chloro-4-fluoro-benzoylamino)- 3,4-dihydro-2,2-dimethyl-2H-benzo[b]pyran-3S-ol as a potential antimigraine agent. |
| AID184101 | In vivo percent increase in seizure threshold in rat MEST model at the dose of 3 mg/kg p.o. recorded 4 hr post dose | 1999 | Bioorganic & medicinal chemistry letters, Jan-18, Volume: 9, Issue:2 | Identification of (-)-cis-6-acetyl-4S-(3-chloro-4-fluoro-benzoylamino)- 3,4-dihydro-2,2-dimethyl-2H-benzo[b]pyran-3S-ol as a potential antimigraine agent. |
| AID197545 | Ability to displace [3H]- SB-204269 in the rat forebrain | 1999 | Bioorganic & medicinal chemistry letters, Jan-18, Volume: 9, Issue:2 | Identification of (-)-cis-6-acetyl-4S-(3-chloro-4-fluoro-benzoylamino)- 3,4-dihydro-2,2-dimethyl-2H-benzo[b]pyran-3S-ol as a potential antimigraine agent. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 1 (2.56) | 18.2507 |
| 2000's | 20 (51.28) | 29.6817 |
| 2010's | 10 (25.64) | 24.3611 |
| 2020's | 8 (20.51) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.
| This Compound (34.35) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 6 (15.00%) | 5.53% |
| Reviews | 10 (25.00%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 24 (60.00%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||