258:
31:
1279:
334:
524:
knock-out mice; inhibition of the growth of malignancy in rodents; stimulation of the regeneration of tail-fin and heart muscle in zebrafish; stimulation of regenerative repair of myocardial infarction and traumatic limb muscle injury in adult mice; prevention of aortic valve calcification in a mouse
528:
Demonstrations of trodusquemine's neuroprotective effects include reversal of memory impairment, normalization of behavior, reduction of neuronal loss and increase in healthspan and lifespan in mouse models of
Alzheimer's disease; reduction in alpha-synuclein aggregation and increase in healthspan
542:
Although the physiological basis for the healthy lifespan of certain shark species remains unknown, trodusquemine targets well-recognized aging associated processes at both the cellular level and in vivo across many species. These observations conducted in different laboratories suggest that
376:
InChI=1S/C37H72N4O5S/c1-26(2)34(46-47(43,44)45)13-10-27(3)30-11-12-31-35-32(15-17-37(30,31)5)36(4)16-14-29(24-28(36)25-33(35)42)41-23-9-22-40-20-7-6-19-39-21-8-18-38/h26-35,39-42H,6-25,38H2,1-5H3,(H,43,44,45)/t27-,28-,29+,30-,31+,32+,33-,34-,35+,36+,37-/m1/s1
525:
atheroma model; stimulation of T-cell anti-tumor immunity in a mouse model; correction of systemic and hepatic inflammation, insulin resistance and hepatic dysfunction in horses suffering from equine metabolic syndrome.
645:
Limbocker R, Errico S, Barbut D, Knowles TP, Vendruscolo M, Chiti F, et al. (April 2022). "Squalamine and trodusquemine: two natural products for neurodegenerative diseases, from physical chemistry to the clinic".
784:
Zasloff M, Williams JI, Chen Q, Anderson M, Maeder T, Holroyd K, et al. (May 2001). "A spermine-coupled cholesterol metabolite from the shark with potent appetite suppressant and antidiabetic properties".
748:
Lantz KA, Hart SG, Planey SL, Roitman MF, Ruiz-White IA, Wolfe HR, et al. (August 2010). "Inhibition of PTP1B by trodusquemine (MSI-1436) causes fat-specific weight loss in diet-induced obese mice".
1195:
Perni M, Flagmeier P, Limbocker R, Cascella R, Aprile FA, Galvagnion C, et al. (August 2018). "Multistep
Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine".
520:). Other effects of trodusquemine include amelioration of the metabolic syndrome in mouse models of insulin resistance; correction of hepatic steatosis in ob/ob mice; reversal of atherosclerosis in
437:
properties. Phase I clinical trials of trodusquemine have demonstrated good tolerability, but several planned phase II trials were halted due to financial difficulties of the developer.
51:
1097:"The PTP1B inhibitor MSI-1436 ameliorates liver insulin sensitivity by modulating autophagy, ER stress and systemic inflammation in Equine metabolic syndrome affected horses"
565:, which lack a robust adaptive immune system. It was hypothesized that their innate immunity might be conferred by endogenous production of antimicrobial compounds.
895:"Pharmacological inhibition of protein tyrosine phosphatase 1B protects against atherosclerotic plaque formation in the LDLR-/- mouse model of atherosclerosis"
348:
83:
propylamino]-7-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopentaphenanthren-17-yl]-2-methylheptan-3-yl] hydrogen sulfate
823:
Ahima RS, Patel HR, Takahashi N, Qi Y, Hileman SM, Zasloff MA (July 2002). "Appetite suppression and weight reduction by a centrally active aminosterol".
1299:
603:
Rao MN, Shinnar AE, Noecker LA, Chao TL, Feibush B, Snyder B, et al. (May 2000). "Aminosterols from the dogfish shark
Squalus acanthias".
457:
with a hydroxyl group at C-7 and sulfate group at C-24; spermine is conjugated to the steroid moiety at C-3. It is structurally similar to
858:
Takahashi N, Qi Y, Patel HR, Ahima RS (September 2004). "A novel aminosterol reverses diabetes and fatty liver disease in obese mice".
539:; Trodusquemine may exert its effects by targeting specific centers in the brain. Trodusquemine may also have anxiolytic properties.
368:
75:
1048:"PTP1B Inhibition Improves Mitochondrial Dynamics to Alleviate Calcific Aortic Valve Disease Via Regulating OPA1 Homeostasis"
1269:
177:
696:"From Marine Metabolites to the Drugs of the Future: Squalamine, Trodusquemine, Their Steroid and Triterpene Analogues"
582:
512:
Trodusquemine suppresses appetite, promotes weight loss, and rescues hyperglycemia in genetic mouse models of obesity (
1304:
237:
999:"The protein tyrosine phosphatase 1B inhibitor MSI-1436 stimulates regeneration of heart and multiple other tissues"
1309:
502:
1324:
586:
1329:
430:
1241:
536:
530:
426:
410:
226:
474:
1319:
494:
253:
1314:
1148:"Neuronal Protein Tyrosine Phosphatase 1B Hastens Amyloid β-Associated Alzheimer's Disease in Mice"
92:
1222:
1177:
1128:
1077:
1028:
976:
924:
875:
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802:
766:
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673:
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557:
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166:
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1204:
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1108:
1067:
1059:
1018:
1010:
966:
958:
914:
906:
867:
832:
794:
758:
717:
707:
663:
655:
612:
486:
274:
101:
947:"PTP1B Is an Intracellular Checkpoint that Limits T-cell and CAR T-cell Antitumor Immunity"
186:
1283:
893:
Thompson D, Morrice N, Grant L, Le Sommer S, Lees EK, Mody N, et al. (October 2017).
517:
418:
414:
257:
1123:
1172:
1147:
1146:
Ricke KM, Cruz SA, Qin Z, Farrokhi K, Sharmin F, Zhang L, et al. (February 2020).
1072:
1047:
1023:
998:
971:
946:
919:
894:
722:
1293:
544:
406:
1095:
Bourebaba L, Serwotka-Suszczak A, Pielok A, Sikora M, Mularczyk M, Marycz K (2023).
126:
1163:
562:
521:
422:
1063:
962:
555:
Trodusquemine was originally isolated from liver extracts of the spiny dogfish (
513:
450:
1208:
1113:
1096:
871:
836:
1014:
997:
Smith AM, Maguire-Nguyen KK, Rando TA, Zasloff MA, Strange KB, Yin VP (2017).
462:
458:
454:
434:
310:
157:
22:
395:
1226:
1181:
1132:
1081:
1032:
980:
928:
879:
844:
806:
798:
770:
731:
677:
624:
30:
945:
Wiede F, Lu KH, Du X, Zeissig MN, Xu R, Goh PK, et al. (March 2022).
762:
712:
695:
485:
value of 1 μmol/L. Inhibition of PTP1B prevents dephosphorylation of the
446:
137:
1217:
668:
146:
910:
659:
398:
112:
1046:
Liu F, Chen J, Hu W, Gao C, Zeng Z, Cheng S, et al. (July 2022).
616:
561:). It was discovered through a search for antimicrobial compounds in
217:
206:
478:
402:
333:
324:
787:
International
Journal of Obesity and Related Metabolic Disorders
694:
Kazakova O, Giniyatullina G, Babkov D, Wimmer Z (January 2022).
482:
356:
C(CC(C(C)C)OS(=O)(=O)O)1CC21(CC32(C43(CC(C4)NCCCNCCCCNCCCN)C)O)C
197:
242:
543:
Trodusquemine represents a novel endogenous vertebrate
405:(PTP1B) activity. The compound exhibits broad-spectrum
1267:
489:, thereby increasing insulin signaling and lowering
493:. Trodusquemine also demonstrates affinity for the
322:
309:
273:
268:
236:
216:
196:
176:
156:
136:
111:
91:
66:
50:
42:
37:
125:
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940:
938:
100:
818:
816:
743:
741:
689:
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640:
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598:
596:
8:
21:
700:International Journal of Molecular Sciences
256:
165:
29:
1216:
1171:
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1112:
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1022:
970:
918:
721:
711:
667:
185:
1274:
574:
373:
353:
252:
145:
80:
20:
583:"Molecule of the Week: Trodusquemine"
225:
7:
1052:JACC. Basic to Translational Science
473:Trodusquemine is a non-competitive
205:
116:
14:
453:. The steroid ring consists of a
1277:
1242:"Helping Brains Relieve Anxiety"
291:
285:
1246:Chemical & Engineering News
479:protein tyrosine phosphatase 1B
403:protein tyrosine phosphatase 1B
381:Key:WUJVPODXELZABP-FWJXURDUSA-N
1300:Drugs not assigned an ATC code
1164:10.1523/JNEUROSCI.2120-19.2019
303:
297:
279:
1:
1064:10.1016/j.jacbts.2022.03.002
963:10.1158/2159-8290.CD-21-0694
465:moiety instead of spermine.
1152:The Journal of Neuroscience
605:Journal of Natural Products
1346:
1240:Torrice M (6 March 2015).
1209:10.1021/acschembio.8b00466
1114:10.3389/fendo.2023.1149610
1101:Frontiers in Endocrinology
872:10.1016/j.jhep.2004.05.006
837:10.2337/diabetes.51.7.2099
503:norepinephrine transporter
269:Chemical and physical data
1015:10.1038/s41536-017-0008-1
1003:npj Regenerative Medicine
899:Clinical Science (London)
587:American Chemical Society
401:conjugate) that inhibits
364:
344:
71:
28:
751:Obesity (Silver Spring)
648:Natural Product Reports
799:10.1038/sj.ijo.0801599
409:activity and numerous
860:Journal of Hepatology
1197:ACS Chemical Biology
763:10.1038/oby.2009.444
713:10.3390/ijms23031075
495:dopamine transporter
537:Parkinson's disease
461:, which features a
445:Trodusquemine is a
394:is an aminosterol (
25:
1305:Experimental drugs
911:10.1042/CS20171066
660:10.1039/d1np00042j
529:and lifespan in a
1310:Enzyme inhibitors
905:(20): 2489–2501.
617:10.1021/np990514f
558:Squalus acanthias
389:
388:
335:Interactive image
238:CompTox Dashboard
16:Chemical compound
1337:
1325:Secondary amines
1282:
1281:
1280:
1273:
1262:
1261:
1259:
1257:
1237:
1231:
1230:
1220:
1203:(8): 2308–2319.
1192:
1186:
1185:
1175:
1158:(7): 1581–1593.
1143:
1137:
1136:
1126:
1116:
1092:
1086:
1085:
1075:
1043:
1037:
1036:
1026:
994:
985:
984:
974:
951:Cancer Discovery
942:
933:
932:
922:
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884:
883:
855:
849:
848:
820:
811:
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781:
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736:
735:
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715:
691:
682:
681:
671:
642:
629:
628:
600:
591:
590:
589:. 13 April 2015.
579:
516:) and diabetes (
501:0.4 μmol/L) and
487:insulin receptor
481:(PTP1B) with an
337:
317:
305:
299:
293:
287:
281:
261:
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246:
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33:
26:
24:
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1253:
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1234:
1194:
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1189:
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1144:
1140:
1094:
1093:
1089:
1045:
1044:
1040:
996:
995:
988:
944:
943:
936:
892:
891:
887:
857:
856:
852:
831:(7): 2099–104.
822:
821:
814:
783:
782:
778:
747:
746:
739:
693:
692:
685:
644:
643:
632:
602:
601:
594:
581:
580:
576:
571:
553:
508:
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471:
443:
419:atherosclerotic
415:neuroprotective
385:
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377:
372:
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360:
357:
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254:DTXSID701317590
240:
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132:
115:
107:
87:
84:
79:
78:
62:
17:
12:
11:
5:
1343:
1341:
1333:
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1330:Sulfate esters
1327:
1322:
1317:
1312:
1307:
1302:
1292:
1291:
1287:
1286:
1264:
1263:
1232:
1187:
1138:
1087:
1058:(7): 697–712.
1038:
986:
957:(3): 752–773.
934:
885:
850:
812:
776:
757:(8): 1516–23.
737:
683:
654:(4): 742–753.
630:
592:
573:
572:
570:
567:
552:
549:
506:
498:
470:
467:
449:metabolite of
442:
439:
427:antiangiogenic
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13:
10:
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842:
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834:
830:
826:
819:
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796:
793:(5): 689–97.
792:
788:
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772:
768:
764:
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752:
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742:
738:
733:
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550:
548:
546:
545:geroprotector
540:
538:
534:
533:
526:
523:
519:
515:
510:
509:0.7 μmol/L).
504:
496:
492:
491:blood glucose
488:
484:
480:
477:inhibitor of
476:
468:
466:
464:
460:
456:
452:
448:
440:
438:
436:
432:
428:
424:
420:
416:
412:
408:
407:antimicrobial
404:
400:
397:
393:
392:Trodusquemine
379:
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354:
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343:
336:
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55:
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49:
45:
41:
38:Clinical data
36:
32:
27:
23:Trodusquemine
19:
1254:. Retrieved
1249:
1245:
1235:
1218:10261/253531
1200:
1196:
1190:
1155:
1151:
1141:
1104:
1100:
1090:
1055:
1051:
1041:
1006:
1002:
954:
950:
902:
898:
888:
866:(3): 391–8.
863:
859:
853:
828:
824:
790:
786:
779:
754:
750:
703:
699:
669:2158/1284768
651:
647:
611:(5): 631–5.
608:
604:
577:
563:Squaliformes
556:
554:
541:
531:
527:
511:
472:
469:Pharmacology
444:
411:regenerative
391:
390:
227:ChEMBL508583
18:
1320:Cholestanes
1107:: 1149610.
706:(3): 1075.
451:cholesterol
431:antiobesity
318: g·mol
102:186139-09-3
67:Identifiers
43:Other names
1315:Polyamines
1294:Categories
569:References
475:allosteric
463:spermidine
459:squalamine
455:cholestane
435:anxiolytic
323:3D model (
311:Molar mass
187:KKC12PIF16
158:ChemSpider
93:CAS Number
76:IUPAC name
535:model of
532:C.elegans
441:Chemistry
423:antitumor
396:polyamine
1284:Medicine
1227:29953201
1182:31915254
1133:37020593
1124:10067883
1082:35958694
1033:29302341
981:34794959
929:28899902
880:15336441
845:12086938
825:Diabetes
807:11360152
771:20075852
732:35162998
678:34698757
625:10843574
447:spermine
138:DrugBank
52:ATC code
46:MSI-1436
1173:7044730
1073:9357565
1024:5677970
972:8904293
920:6365594
723:8834734
551:History
417:, anti-
399:steroid
275:Formula
167:8093615
147:DB06333
127:9917968
113:PubChem
1270:Portal
1256:30 May
1225:
1180:
1170:
1131:
1121:
1080:
1070:
1031:
1021:
979:
969:
927:
917:
878:
843:
805:
769:
730:
720:
676:
623:
433:, and
349:SMILES
316:685.07
218:ChEMBL
207:D06252
1009:: 4.
518:db/db
514:ob/ob
369:InChI
325:JSmol
1258:2024
1252:(10)
1223:PMID
1178:PMID
1129:PMID
1078:PMID
1029:PMID
977:PMID
925:PMID
876:PMID
841:PMID
803:PMID
767:PMID
728:PMID
674:PMID
621:PMID
522:LDLR
483:IC50
198:KEGG
178:UNII
59:None
1213:hdl
1205:doi
1168:PMC
1160:doi
1119:PMC
1109:doi
1068:PMC
1060:doi
1019:PMC
1011:doi
967:PMC
959:doi
915:PMC
907:doi
903:131
868:doi
833:doi
795:doi
759:doi
718:PMC
708:doi
664:hdl
656:doi
613:doi
505:(IC
497:(IC
243:EPA
117:CID
1296::
1250:93
1248:.
1244:.
1221:.
1211:.
1201:13
1199:.
1176:.
1166:.
1156:40
1154:.
1150:.
1127:.
1117:.
1105:14
1103:.
1099:.
1076:.
1066:.
1054:.
1050:.
1027:.
1017:.
1005:.
1001:.
989:^
975:.
965:.
955:12
953:.
949:.
937:^
923:.
913:.
901:.
897:.
874:.
864:41
862:.
839:.
829:51
827:.
815:^
801:.
791:25
789:.
765:.
755:18
753:.
740:^
726:.
716:.
704:23
702:.
698:.
686:^
672:.
662:.
652:39
650:.
633:^
619:.
609:63
607:.
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304:S
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295:4
292:N
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