WIN 18446 : A carboxamide that is 1,8-diaminooctane in which a hydrogen attached to each of the amino groups has been replaced by a dichloroacetyl group. Inhibitor of aldehyde dehydrogenase 1a2 (ALDH1a2). Inhibits the biosynthesis of retinoic acid from retinol in neonatal and adult murine testis. It down-regulates sex related genes in zebrafish. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]
| ID Source | ID |
|---|---|
| PubMed CID | 15134 |
| CHEMBL ID | 3276621 |
| CHEBI ID | 90441 |
| SCHEMBL ID | 5998063 |
| MeSH ID | M0043108 |
| Synonym |
|---|
| acetamide, n,n'-1,8-octanediylbis(2,2-dichloro- |
| brn 2136774 |
| acetamide, n,n'-octamethylenebis(2,2-dichloro- |
| einecs 216-033-0 |
| ai3-26433 |
| n,n'-bis(dichloroacetyl)-1,8-octamethylenediamine |
| bis-diamine |
| c12h20cl4n2o2 |
| acetamide, n,n',1,8-octanediylbis(2,2-dichloro- |
| n,n'-octamethylenebis(2,2-dichloro-n-ethylacetamide) |
| n,n'-octamethylenebis(2,2-dichloroacetamide) |
| n,n'-octamethylenebis(dichloroacetamide) |
| fertilysine |
| win-18446 |
| fertilysine n |
| n,n'-bis(dichloracetyl)-1,8-octanediamine |
| n,n-bis(dichloroacetyl)-1,8-octanediamine |
| bisdiamine |
| nsc 59354 |
| n,n'-bis(dichloroacetyl)-1,8-diaminooctane |
| r-010-tk |
| nsc-59354 |
| fertilysin |
| win 18441 |
| acetamide,n'-1,8-octanediylbis[2,2-dichloro- |
| win 18,446 |
| win 18446 |
| wln: gyg&vm8mvyg&g |
| n,2-dichloroactamide) |
| n,8-diaminooctane |
| 1477-57-2 |
| n,2-dichloroacetamide) |
| nsc59354 |
| acetamide,n'-octamethylenebis[2,2-dichloro- |
| NCIOPEN2_007966 |
| 2,2-dichloro-n-[8-[(2,2-dichloroacetyl)amino]octyl]acetamide |
| n,n'-(octane-1,8-diyl)bis(2,2-dichloroacetamide) |
| AKOS003885063 |
| unii-3f56ra64jn |
| 3f56ra64jn , |
| GEO-02058 |
| FT-0629400 |
| n,n'-octamethylene bis(2,2-dichloro acetamide) |
| n,n'-1,8-octanediylbis(2,2-dichloroacetamide) |
| fertilysin [mi] |
| CHEMBL3276621 , |
| chebi:90441 , |
| acetamide,n,n'-1,8-octanediylbis[2,2-dichloro- |
| SCHEMBL5998063 |
| bis-dichloracetyl-octamethylendiamin |
| 2,2-dichloro-n-(8-[(dichloroacetyl)amino]octyl)acetamide # |
| acetamide, n,n'-octamethylenebis[2,2-dichloro- |
| n,n'-bis(dichloroacetyl)-1,8-octanediamine |
| acetamide, n,n'-1,8-octanediylbis[2,2-dichloro- |
| FAOMZVDZARKPFJ-UHFFFAOYSA-N |
| win18446 |
| n,n'-octane-1,8-diylbis(2,2-dichloroacetamide) |
| DTXSID80163783 |
| n,n'-octmethylenebis (dichloroacetamide) |
| mfcd00000841 |
| CS-W011810 |
| J-008406 |
| NCGC00387188-01 |
| Q27162547 |
| DS-18469 |
| C72811 |
| bdbm50459608 |
| A884401 |
| n,n-octamethylenebis(dichloroacetamide) |
| HY-W011094 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " The bisdiamine WIN 18,446, has proven safe and effective in grey wolves, domestic dogs, rats, and humans, but the unique drug metabolism of cats make extrapolation to felids inappropriate." | ( Efficacy, safety and reversibility of bisdiamine as a male contraceptive in cats. Asa, C; Chassy, LM; Munson, L, 2004) | 0.32 |
| Excerpt | Reference | Relevance |
|---|---|---|
| "The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs." | ( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019) | 0.51 |
| Excerpt | Relevance | Reference |
|---|---|---|
| " Similarly, oral dosing of WIN 18,446, which inhibits testicular retinoic acid biosynthesis, effectively contracepts rabbits." | ( New approaches to male non-hormonal contraception. Amory, JK; Nya-Ngatchou, JJ, 2013) | 0.39 |
| Role | Description |
|---|---|
| EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitor | An EC 1.2.1.* (oxidoreductase acting on donor aldehyde/oxo group with NAD(+) or NADP(+) as acceptor) inhibitor that interferes with the action of aldehyde dehydrogenase (NAD(+)), EC 1.2.1.3. |
| [role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Class | Description |
|---|---|
| organochlorine compound | An organochlorine compound is a compound containing at least one carbon-chlorine bond. |
| secondary carboxamide | A carboxamide resulting from the formal condensation of a carboxylic acid with a primary amine; formula RC(=O)NHR(1). |
| [compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Retinal dehydrogenase 2 | Homo sapiens (human) | Ki | 0.0560 | 0.0560 | 0.0560 | 0.0560 | AID1387302 |
| Retinal dehydrogenase 1 | Homo sapiens (human) | Ki | 0.2850 | 0.2850 | 0.7850 | 1.2000 | AID1387301 |
| Aldehyde dehydrogenase, mitochondrial | Homo sapiens (human) | IC50 (µMol) | 0.2293 | 0.0400 | 3.4079 | 9.0000 | AID1418961 |
| Aldehyde dehydrogenase family 1 member A3 | Homo sapiens (human) | Ki | 0.2610 | 0.2610 | 0.2610 | 0.2610 | AID1387303 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Retinal dehydrogenase 2 | Gallus gallus (chicken) | EC50 (µMol) | 0.0445 | 0.0445 | 0.0445 | 0.0445 | AID1418989 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| AID1387303 | Inhibition of human ALDH1A3 | 2018 | Journal of medicinal chemistry, 10-11, Volume: 61, Issue:19 | Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer Chemotherapy. |
| AID1418961 | Inhibition of N-terminal His6-tagged recombinant human mitochondrial ALDH2 using propionaldehyde as substrate preincubated for 20 mins to 1 hr followed by substrate addition and measured for 5 mins in presence of NADH by fluorescence assay | 2018 | Bioorganic & medicinal chemistry, 12-01, Volume: 26, Issue:22 | Design, synthesis, and ex vivo evaluation of a selective inhibitor for retinaldehyde dehydrogenase enzymes. |
| AID1387302 | Inhibition of human ALDH1A2 | 2018 | Journal of medicinal chemistry, 10-11, Volume: 61, Issue:19 | Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer Chemotherapy. |
| AID1418990 | Inhibition of RALDH2 in living intact choroid isolated from 4 day recovering chick eyes assessed as inhibition of ATRA synthesis at 0.1 uM after 24 hrs in presence of ATRA and NAD+ | 2018 | Bioorganic & medicinal chemistry, 12-01, Volume: 26, Issue:22 | Design, synthesis, and ex vivo evaluation of a selective inhibitor for retinaldehyde dehydrogenase enzymes. |
| AID1387301 | Inhibition of human ALDH1A1 | 2018 | Journal of medicinal chemistry, 10-11, Volume: 61, Issue:19 | Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer Chemotherapy. |
| AID1150560 | Antispermatogenic activity in Long-Evans rat assessed as reduction of testes weight at a dose equimolecular to 400 mg/kg of 1-(4-chlorobenzyl)-1H-indazole-3-carboxylic acid administered orally as single dose measured after 5 days | 1976 | Journal of medicinal chemistry, Jun, Volume: 19, Issue:6 | 1-Halobenzyl-1H-indazole-3-carboxylic acids. A new class of antispermatogenic agents. |
| AID1418989 | Inhibition of RALDH2 in living intact choroid isolated from 4 day recovering chick eyes assessed as inhibition of ATRA synthesis after 24 hrs in presence of ATRA and NAD+ | 2018 | Bioorganic & medicinal chemistry, 12-01, Volume: 26, Issue:22 | Design, synthesis, and ex vivo evaluation of a selective inhibitor for retinaldehyde dehydrogenase enzymes. |
| AID1418991 | Inhibition of RALDH2 in living intact choroid isolated from 4 day recovering chick eyes assessed as inhibition of ATRA synthesis at 10 uM after 24 hrs in presence of ATRA and NAD+ | 2018 | Bioorganic & medicinal chemistry, 12-01, Volume: 26, Issue:22 | Design, synthesis, and ex vivo evaluation of a selective inhibitor for retinaldehyde dehydrogenase enzymes. |
| AID1419019 | Inhibition of RALDH2 in living intact choroid isolated from normal chick eyes assessed as inhibition of ATRA synthesis after 24 hrs in presence of ATRA and NAD+ | 2018 | Bioorganic & medicinal chemistry, 12-01, Volume: 26, Issue:22 | Design, synthesis, and ex vivo evaluation of a selective inhibitor for retinaldehyde dehydrogenase enzymes. |
| AID1418988 | Inhibition of RALDH2 in living intact choroid isolated from 4 day recovering chick eyes assessed as inhibition of ATRA synthesis at 1 uM after 24 hrs in presence of ATRA and NAD+ | 2018 | Bioorganic & medicinal chemistry, 12-01, Volume: 26, Issue:22 | Design, synthesis, and ex vivo evaluation of a selective inhibitor for retinaldehyde dehydrogenase enzymes. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 9 (25.00) | 18.7374 |
| 1990's | 5 (13.89) | 18.2507 |
| 2000's | 6 (16.67) | 29.6817 |
| 2010's | 12 (33.33) | 24.3611 |
| 2020's | 4 (11.11) | 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 (26.95) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 0 (0.00%) | 5.53% |
| Reviews | 1 (2.50%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 39 (97.50%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||