339:
InChI=1S/C158H249N53O47S11/c1-77(2)55-96-138(241)205-105(144(247)186-86(125(165)228)28-18-47-173-156(166)167)70-264-262-68-103-131(234)177-63-115(217)176-64-116(218)183-87(25-12-15-44-159)128(231)178-65-117(219)184-88(29-19-48-174-157(168)169)129(232)179-66-118(220)185-89(26-13-16-45-160)133(236)202-107-72-267-269-75-110-149(252)195-98(56-81-23-10-9-11-24-81)143(246)208-124(80(5)213)154(257)209-123(79(4)212)153(256)199-102(61-122(226)227)141(244)196-99(58-83-62-172-76-181-83)139(242)189-92(37-39-113(163)215)136(239)190-94(42-53-260-7)132(235)182-78(3)126(229)187-91(30-20-49-175-158(170)171)134(237)188-90(27-14-17-46-161)135(238)203-108(73-266-265-71-106(146(249)193-96)204-137(240)93(38-40-114(164)216)191-151(254)111-31-21-50-210(111)119(221)67-180-130(233)97(194-147(107)250)57-82-33-35-84(214)36-34-82)148(251)198-100(59-120(222)223)140(243)197-101(60-121(224)225)142(245)206-109(150(253)201-103)74-268-263-69-104(200-127(230)85(162)41-52-259-6)145(248)192-95(43-54-261-8)155(258)211-51-22-32-112(211)152(255)207-110/h9-11,23-24,33-36,62,76-80,85-112,123-124,212-214H,12-22,25-32,37-61,63-75,159-162H2,1-8H3,(H2,163,215)(H2,164,216)(H2,165,228)(H,172,181)(H,176,217)(H,177,234)(H,178,231)(H,179,232)(H,180,233)(H,182,235)(H,183,218)(H,184,219)(H,185,220)(H,186,247)(H,187,229)(H,188,237)(H,189,242)(H,190,239)(H,191,254)(H,192,248)(H,193,249)(H,194,250)(H,195,252)(H,196,244)(H,197,243)(H,198,251)(H,199,256)(H,200,230)(H,201,253)(H,202,236)(H,203,238)(H,204,240)(H,205,241)(H,206,245)(H,207,255)(H,208,246)(H,209,257)(H,222,223)(H,224,225)(H,226,227)(H4,166,167,173)(H4,168,169,174)(H4,170,171,175)/t78-,79+,80+,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,123-,124-/m0/s1
217:
316:
363:
C1C(=O)N(C(=O)N(C(=O)N2CSSC3C(=O)N(C(=O)N(CSSC4C(=O)NCC(=O)NCC(=O)N(C(=O)NCC(=O)N(C(=O)NCC(=O)N(C(=O)N(CSSC(C(=O)N(C(=O)N(C(=O)N(C(=O)N(C(=O)N(C(=O)N(C(=O)N(C(=O)N1)CCSC)CCC(=O)N)CC5=CNC=N5)CC(=O)O)(C)O)(C)O)CC6=CC=CC=C6)NC(=O)7CCCN7C(=O)(NC(=O)(CSSC(C(=O)N4)NC(=O)(NC(=O)(NC2=O)CC(=O)O)CC(=O)O)NC(=O)(CCSC)N)CCSC)C(=O)N(C(=O)NCC(=O)N8CCC8C(=O)N(C(=O)N3)CCC(=O)N)CC9=CC=C(C=C9)O)CCCCN)CCCNC(=N)N)CCCCN)C(=O)N(CCCNC(=N)N)C(=O)N)CC(C)C)CCCCN)CCCNC(=N)N
581:
and pincer legs that was complete about forty seconds later. Within ±90 s of injection the tail musculature was immobilized. No recovery was noted for 6 hours, at which time the crayfish were destroyed. At 0.5 μg/g, chlorotoxin induced the same progressive paralysis with a slower onset. Recovery of crayfish was noted after 2 hours. The injection on insects produced similar results to those observed in crayfish.
446:
24:
580:
Chlorotoxin immobilizes the envenomated prey. Duration of paralysis depends on the amount of chlorotoxin injected. In crayfish, chlorotoxin at 1.23-2.23 μg/g body wt produced a loss of motor control beginning about 20 seconds after injection which progressed to a rigid paralysis of the walking
608:
TM-601 which is the synthetic version of chlorotoxin is under phase II clinical trial. Iodine-131-TM-601 is used to treat malignant glioma. TM-601 is also a candidate for targeting gliomas because it crosses blood-brain and tissue barriers and binds to malignant brain tumor cells without affecting
632:
spectrum and hence can be visualized in the operating room with the aid of infrared glasses. Studies in mouse models have shown that CTX:Cy5.5 can identify tumors with as few as 2000 cancer cells, making it 500 times more sensitive than MRI. Treated animals exhibited no neurologic or behavioral
604:
A report showed the anti-invasive effect of chlorotoxin on glioma cells mediated by its interaction with MMP-2, which allows the penetration of normal and tumor cells through tissue barriers. Chlorotoxin exerts a dual effect on MMP-2: it inhibits the enzymatic activity of MMP-2 and causes a
571:
Using a recombinant chlorotoxin it was demonstrated that chlorotoxin specifically and selectively interacts with MMP-2 isoforms which are specifically upregulated in gliomas and related cancers, but are not normally expressed in brain.
627:
to distinguish cancer cells from the surrounding normal cells. This could enable surgeons to remove cancerous cells without injuring the surrounding healthy tissue. CTX:Cy5.5 is a fluorescent molecule emitting photons in the near
589:
The fact that chlorotoxin binds preferentially to glioma cells compared with non-neoplastic cells or normal brain has allowed the development of new methods for the treatment and diagnosis of several types of cancer.
605:
reduction in the surface expression of MMP-2. This result implies the use of chlorotoxin as a highly effective drug of therapeutic potential for diseases that involve the activity of MMP-2.
991:
Mamelak AN, Rosenfeld S, Bucholz R, et al. (August 2006). "Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma".
831:
Lippens G, Najib J, Wodak SJ, Tartar A (January 1995). "NMR sequential assignments and solution structure of chlorotoxin, a small scorpion toxin that blocks chloride channels".
1142:
Fidel, J.; Kennedy, K. C.; Dernell, W. S.; Hansen, S.; Wiss, V.; Stroud, M. R.; Molho, J. I.; Knoblaugh, S. E.; Meganck, J.; Olson, J. M.; Rice, B.; Parrish-Novak, J. (2015).
459:
948:
Lyons SA, O'Neal J, Sontheimer H (August 2002). "Chlorotoxin, a scorpion-derived peptide, specifically binds to gliomas and tumors of neuroectodermal origin".
355:
1116:
624:
601:
chloride fluxes but this interaction does not happen for the neurons and normal glial cells. This suggests a potential treatment for cancer.
655:
suggests using a scorpion derived toxin to paint the pancreas and view it under infrared light to look for tumors too small to detect by
868:"Isolation and characterization of a novel lepidopteran-selective toxin from the venom of South Indian red scorpion, Mesobuthus tamulus"
1237:
1227:
633:
deficits, and postmortem studies revealed no evidence of neuropathy. In 2015, clinical trials were beginning for this "Tumor Paint."
568:
for Cl channels and it blocks small conductance chloride channels. Each chloride channel can be closed by only one ligand molecule.
330:
676:
1144:"Preclinical validation of the utility of BLZ-100 in providing fluorescence contrast for imaging canine spontaneous solid tumors"
273:
1232:
294:
704:
DeBin JA, Strichartz GR (1991). "Chloride channel inhibition by the venom of the scorpion
Leiurus quinquestriatus".
466:
1222:
918:
793:
794:"Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion"
642:
521:
508:
cells has allowed the development of methods for the treatment and diagnosis of several types of cancer.
36:
612:
Phase II trials are being conducted on the use of chlorotoxin for imaging and radio therapy in glioma.
1120:
311:
183:
1191:
973:
1077:"Tumor paint: a chlorotoxin:Cy5.5 bioconjugate for intraoperative visualization of cancer foci"
1173:
1098:
1057:
1008:
965:
930:
899:
848:
813:
767:
721:
647:
549:
237:
1163:
1155:
1088:
1047:
1039:
1000:
957:
889:
879:
840:
805:
757:
713:
501:
378:
193:
282:
315:
1168:
1143:
1052:
1027:
545:
517:
437:
593:
Chlorotoxin has the ability to interact with chloride channels in membrane protein in
1216:
894:
867:
717:
652:
598:
262:
809:
977:
553:
493:
1159:
1093:
1076:
866:
Wudayagiri R, Inceoglu B, Herrmann R, Derbel M, Choudary PV, Hammock BD (2001).
623:, was used by researchers at Seattle Children's Hospital Research Institute and
616:
1043:
532:
Chlorotoxin is a small toxin and at pH 7 is highly positively charged. It is a
537:
482:
418:
228:
1004:
615:
Chlorotoxin:Cy5.5 (CTX:Cy5.5), which is a bioconjugate of chlorotoxin and a
1177:
1102:
1061:
1012:
969:
903:
884:
771:
762:
745:
934:
852:
817:
746:"Chlorotoxin inhibits glioma cell invasion via matrix metalloproteinase-2"
725:
629:
541:
844:
23:
961:
620:
533:
485:
249:
917:
Soroceanu L, Gillespie Y, Khazaeli MB, Sontheimer H (November 1998).
594:
565:
516:
Chlorotoxin can be purified from crude leiurus, which belongs to the
505:
436:
Except where otherwise noted, data are given for materials in their
163:-argininamide, cyclic (219),(528),(1633),(2035)-tetrakis(disulfide)
1026:
Mark R. Stroud; Stacey J. Hansen; James M. Olson (December 2011).
489:
216:
206:
656:
299:
1075:
Veiseh M, Gabikian P, Bahrami SB, et al. (July 2007).
919:"Use of chlorotoxin for targeting of primary brain tumors"
677:"Chlorotoxin from Leiurus quinquestriatus (north Africa)"
1028:"In Vivo Bio Imaging Using Chlorotoxin Based Conjugates"
564:
Chlorotoxin is the first reported high-affinity peptide
454:
1117:"Tumor Painting Revolutionizes Fight Against Cancer"
792:
DeBin JA, Maggio JE, Strichartz GR (February 1993).
744:
Deshane J, Garner CC, Sontheimer H (February 2003).
504:. The fact that chlorotoxin binds preferentially to
261:
192:
739:
737:
735:
787:
785:
783:
781:
699:
697:
8:
314:
236:
15:
1167:
1092:
1051:
893:
883:
761:
281:
668:
360:
335:
310:
625:Fred Hutchinson Cancer Research Center
342:Key: QPAKKWCQMHUHNI-GQIQPHNSSA-N
7:
171:MCMPCFTTDHQMARKCDDCCGGKGRGKCYGPQCLCR
252:
14:
548:. Chlorotoxin has a considerable
500:) which blocks small-conductance
444:
396:
390:
22:
810:10.1152/ajpcell.1993.264.2.C361
440:(at 25 °C , 100 kPa).
1119:. 15 July 2007. Archived from
408:
402:
384:
1:
1160:10.1158/0008-5472.CAN-15-0471
1094:10.1158/0008-5472.CAN-06-3948
1032:Current Pharmaceutical Design
718:10.1016/0041-0101(91)90128-E
1254:
1044:10.2174/138161211798999375
1238:Chloride channel blockers
1228:Experimental cancer drugs
1192:"Both Sides Now synopsis"
434:
371:
351:
326:
176:
168:
35:
30:
21:
1005:10.1200/JCO.2005.05.4569
597:cells, so this prevents
585:Possible therapeutic use
498:Leiurus quinquestriatus
119:-cysteinylglycylglycyl-
885:10.1186/1471-2091-2-16
763:10.1074/jbc.M205662200
552:to the class of small
494:deathstalker scorpion
845:10.1021/bi00001a003
645:" of medical drama
430: g·mol
18:
1233:Ion channel toxins
962:10.1002/glia.10083
804:(2 Pt 1): C361–9.
637:In popular culture
467:Infobox references
75:-.alpha.-aspartyl-
16:
1154:(20): 4283–4291.
550:sequence homology
536:consisting of 36
502:chloride channels
475:Chemical compound
473:
472:
295:CompTox Dashboard
218:Interactive image
162:
158:
154:
150:
146:
142:
138:
134:
130:
126:
122:
118:
114:
110:
106:
102:
98:
94:
90:
86:
82:
78:
74:
70:
66:
62:
58:
54:
50:
46:
42:
1245:
1207:
1206:
1204:
1202:
1188:
1182:
1181:
1171:
1139:
1133:
1132:
1130:
1128:
1113:
1107:
1106:
1096:
1072:
1066:
1065:
1055:
1023:
1017:
1016:
988:
982:
981:
945:
939:
938:
914:
908:
907:
897:
887:
863:
857:
856:
828:
822:
821:
789:
776:
775:
765:
741:
730:
729:
701:
692:
691:
689:
687:
681:Sigmaaldrich.com
673:
641:In the episode "
609:healthy tissue.
457:
451:
448:
447:
429:
427:
410:
404:
398:
392:
386:
379:Chemical formula
319:
318:
303:
301:
285:
265:
254:
240:
220:
196:
160:
156:
152:
148:
144:
140:
136:
132:
128:
124:
120:
116:
112:
108:
104:
100:
96:
92:
88:
84:
80:
76:
72:
68:
64:
60:
56:
52:
48:
44:
40:
26:
19:
1253:
1252:
1248:
1247:
1246:
1244:
1243:
1242:
1223:Scorpion toxins
1213:
1212:
1211:
1210:
1200:
1198:
1190:
1189:
1185:
1148:Cancer Research
1141:
1140:
1136:
1126:
1124:
1115:
1114:
1110:
1074:
1073:
1069:
1038:(38): 4362–71.
1025:
1024:
1020:
999:(22): 3644–50.
990:
989:
985:
947:
946:
942:
916:
915:
911:
865:
864:
860:
830:
829:
825:
791:
790:
779:
743:
742:
733:
703:
702:
695:
685:
683:
675:
674:
670:
665:
639:
587:
578:
562:
546:disulfide bonds
530:
514:
476:
469:
464:
463:
462: ?)
453:
449:
445:
441:
425:
423:
413:
407:
401:
395:
389:
381:
367:
364:
359:
358:
347:
344:
343:
340:
334:
333:
322:
304:
297:
288:
268:
255:
243:
223:
210:
199:
186:
172:
164:
139:-tyrosylglycyl-
127:-arginylglycyl-
12:
11:
5:
1251:
1249:
1241:
1240:
1235:
1230:
1225:
1215:
1214:
1209:
1208:
1183:
1134:
1123:on 4 June 2016
1108:
1087:(14): 6882–8.
1067:
1018:
993:J. Clin. Oncol
983:
940:
929:(21): 4871–9.
909:
858:
823:
798:Am. J. Physiol
777:
756:(6): 4135–44.
731:
712:(11): 1403–8.
693:
667:
666:
664:
661:
643:Both Sides Now
638:
635:
586:
583:
577:
574:
561:
558:
529:
526:
518:scorpion toxin
513:
510:
474:
471:
470:
465:
443:
442:
438:standard state
435:
432:
431:
421:
415:
414:
411:
405:
399:
393:
387:
382:
377:
374:
373:
369:
368:
366:
365:
362:
354:
353:
352:
349:
348:
346:
345:
341:
338:
337:
329:
328:
327:
324:
323:
321:
320:
312:DTXSID70897247
307:
305:
293:
290:
289:
287:
286:
278:
276:
270:
269:
267:
266:
258:
256:
248:
245:
244:
242:
241:
233:
231:
225:
224:
222:
221:
213:
211:
204:
201:
200:
198:
197:
189:
187:
182:
179:
178:
174:
173:
170:
166:
165:
63:-phenylalanyl-
39:
33:
32:
28:
27:
13:
10:
9:
6:
4:
3:
2:
1250:
1239:
1236:
1234:
1231:
1229:
1226:
1224:
1221:
1220:
1218:
1197:
1193:
1187:
1184:
1179:
1175:
1170:
1165:
1161:
1157:
1153:
1149:
1145:
1138:
1135:
1122:
1118:
1112:
1109:
1104:
1100:
1095:
1090:
1086:
1082:
1078:
1071:
1068:
1063:
1059:
1054:
1049:
1045:
1041:
1037:
1033:
1029:
1022:
1019:
1014:
1010:
1006:
1002:
998:
994:
987:
984:
979:
975:
971:
967:
963:
959:
956:(2): 162–73.
955:
951:
944:
941:
936:
932:
928:
924:
920:
913:
910:
905:
901:
896:
891:
886:
881:
877:
873:
869:
862:
859:
854:
850:
846:
842:
838:
834:
827:
824:
819:
815:
811:
807:
803:
799:
795:
788:
786:
784:
782:
778:
773:
769:
764:
759:
755:
751:
750:J. Biol. Chem
747:
740:
738:
736:
732:
727:
723:
719:
715:
711:
707:
700:
698:
694:
682:
678:
672:
669:
662:
660:
658:
654:
650:
649:
644:
636:
634:
631:
626:
622:
618:
613:
610:
606:
602:
600:
599:transmembrane
596:
591:
584:
582:
575:
573:
569:
567:
559:
557:
555:
554:insectotoxins
551:
547:
543:
539:
535:
527:
525:
523:
519:
511:
509:
507:
503:
499:
495:
491:
488:found in the
487:
484:
480:
468:
461:
456:
439:
433:
422:
420:
417:
416:
383:
380:
376:
375:
370:
361:
357:
350:
336:
332:
325:
317:
313:
309:
308:
306:
296:
292:
291:
284:
280:
279:
277:
275:
272:
271:
264:
260:
259:
257:
251:
247:
246:
239:
235:
234:
232:
230:
227:
226:
219:
215:
214:
212:
208:
203:
202:
195:
191:
190:
188:
185:
181:
180:
175:
167:
123:-lysylglycyl-
38:
34:
29:
25:
20:
1199:. Retrieved
1195:
1186:
1151:
1147:
1137:
1127:11 September
1125:. Retrieved
1121:the original
1111:
1084:
1080:
1070:
1035:
1031:
1021:
996:
992:
986:
953:
949:
943:
926:
922:
912:
875:
871:
861:
839:(1): 13–21.
836:
833:Biochemistry
832:
826:
801:
797:
753:
749:
709:
705:
686:November 30,
684:. Retrieved
680:
671:
646:
640:
614:
611:
607:
603:
592:
588:
579:
570:
563:
531:
515:
497:
478:
477:
177:Identifiers
169:Other names
147:-glutaminyl-
111:-α-aspartyl-
107:-α-aspartyl-
83:-glutaminyl-
17:Chlorotoxin
1201:30 November
872:BMC Biochem
617:fluorescent
538:amino acids
522:superfamily
479:Chlorotoxin
372:Properties
194:163515-35-3
159:-cysteinyl-
151:-cysteinyl-
135:-cysteinyl-
115:-cysteinyl-
103:-cysteinyl-
87:-methionyl-
59:-cysteinyl-
51:-methionyl-
47:-cysteinyl-
43:-methionyl-
1217:Categories
1081:Cancer Res
923:Cancer Res
663:References
619:dye named
544:forming 4
483:amino acid
419:Molar mass
283:06UV5RFW57
229:ChemSpider
205:3D model (
184:CAS Number
79:-histidyl-
71:-threonyl-
67:-threonyl-
37:IUPAC name
542:cysteines
540:, with 8
528:Chemistry
95:-arginyl-
1196:IMDb.com
1178:26471914
1103:17638899
1062:22204434
1013:16877732
970:12112367
904:11782289
772:12454020
630:infrared
576:Toxicity
520:protein
481:is a 36-
263:86278273
238:57582614
155:-leucyl-
143:-prolyl-
91:-alanyl-
55:-prolyl-
1169:4610180
1053:3272502
978:8513870
935:9809993
853:7819188
818:8383429
726:1726031
706:Toxicon
534:peptide
512:Sources
492:of the
486:peptide
460:what is
458: (
250:PubChem
131:-lysyl-
99:-lysyl-
1176:
1166:
1101:
1060:
1050:
1011:
976:
968:
933:
902:
892:
878:: 16.
851:
816:
770:
724:
595:glioma
566:ligand
560:Target
506:glioma
455:verify
452:
356:SMILES
31:Names
974:S2CID
895:64496
653:House
648:House
621:Cy5.5
490:venom
331:InChI
207:JSmol
1203:2015
1174:PMID
1129:2015
1099:PMID
1058:PMID
1009:PMID
966:PMID
950:Glia
931:PMID
900:PMID
849:PMID
814:PMID
768:PMID
722:PMID
688:2021
274:UNII
1164:PMC
1156:doi
1089:doi
1048:PMC
1040:doi
1001:doi
958:doi
890:PMC
880:doi
841:doi
806:doi
802:264
758:doi
754:278
714:doi
657:MRI
428:.71
426:995
394:249
388:158
300:EPA
253:CID
1219::
1194:.
1172:.
1162:.
1152:75
1150:.
1146:.
1097:.
1085:67
1083:.
1079:.
1056:.
1046:.
1036:17
1034:.
1030:.
1007:.
997:24
995:.
972:.
964:.
954:39
952:.
927:58
925:.
921:.
898:.
888:.
874:.
870:.
847:.
837:34
835:.
812:.
800:.
796:.
780:^
766:.
752:.
748:.
734:^
720:.
710:29
708:.
696:^
679:.
659:.
651:,
556:.
524:.
412:11
406:47
400:53
1205:.
1180:.
1158::
1131:.
1105:.
1091::
1064:.
1042::
1015:.
1003::
980:.
960::
937:.
906:.
882::
876:2
855:.
843::
820:.
808::
774:.
760::
728:.
716::
690:.
496:(
450:N
424:3
409:S
403:O
397:N
391:H
385:C
302:)
298:(
209:)
161:L
157:L
153:L
149:L
145:L
141:L
137:L
133:L
129:L
125:L
121:L
117:L
113:L
109:L
105:L
101:L
97:L
93:L
89:L
85:L
81:L
77:L
73:L
69:L
65:L
61:L
57:L
53:L
49:L
45:L
41:L
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
