521:
498:
858:(DMAPP), produced via the mevalonate pathway, to form a carbo-cation via the cleavage of the diphosphates. Once activated, the enzyme umbelliferone 6-prenyltransferase catalyzes a C-alkylation between DMAPP and umbelliferone at the activated position ortho to the phenol, yielding demethylsuberosin. This is then followed by a hydroxylation catalyzed by the enzyme marmesin synthase to yield
791:
29:
1877:
845:
688:(UVA) light from lamps or sunlight. Methoxsalen modifies the way skin cells receive the UVA radiation, allegedly clearing up the disease. Levels of individual patient PUVA exposure were originally determined using the
1224:
203:
148:
1228:
59:
598:
1121:
Marshall SR (June 2006). "Technology insight: ECP for the treatment of GvHD--can we offer selective immune control without generalized immunosuppression?".
1932:
894:
problems are at risk for inflammation and irreparable damage to both liver and skin. The eyes must be protected from UVA radiation. Side effects include
1279:
1391:
696:
after oral ingestion of methoxsalen followed by PUVA therapy. Chemically, methoxsalen belongs to a class of organic natural molecules known as
1485:
1193:
1541:
929:(1920–1980) used the chemical to darken his skin in order to investigate racial segregation in the American South. He wrote the book
1912:
870:. A third hydroxylation by the enzyme psoralen 8-monooxygenase yields xanthotoxol which is followed by a methylation via the enzyme
618:
832:
group. Finally an intramolecular attack from the hydroxyl group of C2' to the carboxylic acid group closes the ring and forms the
1907:
960:
1094:
Fahmy IR, Abu-Shady H (1947). "Ammi majus Linn.; pharmacognostical study and isolation of a crystalline constituent, ammoidin".
1068:
1042:
1922:
871:
258:
188:
77:
1867:
1272:
584:
377:
824:. The 4-coumaric acid is again hydroxylated by cinnamate/coumarate 2-hydroxylase to yield 2,4-dihydroxy-cinnamic acid (
96:
1650:
1502:
855:
848:
477:
1902:
1897:
1927:
1917:
740:
1490:
1265:
914:
817:
133:
516:
1534:
1014:"FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)"
1942:
1937:
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1834:
1013:
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141:
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41:
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917:(known to cause cancer) but is only cancerous when combined with light - UVA radiation.
520:
497:
1723:
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1496:
759:
697:
1891:
1849:
1824:
1819:
1577:
1288:
1243:
825:
813:
809:
808:, which in turn is produced via the shikimate pathway. Phenylalanine is lysated into
794:
775:
693:
509:
216:
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457:
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1401:
1396:
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1328:
721:
665:
560:
357:
719:
In 1947, methoxsalen was isolated (under the name "ammoidin") from the plant
69:
1829:
1769:
1718:
1682:
1622:
1598:
1467:
1444:
1381:
1336:
903:
771:
755:
728:
In 1970, Nielsen extracted 8-methoxypsoralen from four species of the genus
669:
63:
20:
1146:
1107:
790:
626:
InChI=1S/C12H8O4/c1-14-12-10-8(4-5-15-10)6-7-2-3-9(13)16-11(7)12/h2-6H,1H3
1854:
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Botanical
Dermatology: Plants and Plant Products Injurious to the Skin
828:) followed by a bond rotation of the unsaturated bond adjacent to the
1635:
1603:
1519:
895:
673:
437:
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891:
843:
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692:. The scale was developed after patients demonstrated symptoms of
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397:
1523:
1261:
210:
86:
1314:
1021:
1213:(3rd ed.). John Wiley & Sons. pp. 161, 164–165.
854:
The biosynthetic route then continues with the activation of
482:
197:
118:
643:
1865:
1069:"Oxsoralen-Ultra- methoxsalen capsule, liquid filled"
982:
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Medicinal
Natural Products: A Biosynthetic Approach
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35:
770:The biosynthetic pathway is a combination of the
325:
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1172:. Copenhagen: Royal Danish School of Pharmacy.
1096:Quarterly Journal of Pharmacy and Pharmacology
711:. It can also be injected and used topically.
1535:
1273:
750:. An additional 32 species of the genus
8:
465:
95:
19:
1188:. Vancouver: Greengrass. pp. 692–699.
913:Methoxsalen has also been classified as an
1708:
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1520:
1424:
1304:
1280:
1266:
1258:
519:
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365:
27:
1227:. American Cancer Society. Archived from
1043:"Uvadex- methoxsalen injection, solution"
754:were found to contain 5-methoxypsoralen (
684:in conjunction with exposing the skin to
385:
862:. Another hydroxylation is catalyzed by
1872:
944:
623:
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492:
345:
263:
1225:"Known and Probable Human Carcinogens"
992:Therapeutic Goods Administration (TGA)
510:
18:
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7:
170:
160:
1075:. U.S. National Library of Medicine
1049:. U.S. National Library of Medicine
405:
316:
1933:General cytochrome P450 inhibitors
1174:Cited by Mitchell and Rook (1979).
1123:Nature Clinical Practice. Oncology
14:
1170:Coumarins of Umbelliferous plants
1875:
1763:Meroterpene furanocoumarin ether
1651:Umbelliferone 7-apiosylglucoside
961:Therapeutic Goods Administration
804:and as such is synthesized from
544:
46:Oxsoralen, Uvadex, 8-mop, others
872:xanthotoxol O-methyltransferase
631:Key:QXKHYNVANLEOEG-UHFFFAOYSA-N
1244:"Death of John Howard Griffin"
935:(1961) about his experiences.
550:
538:
1:
1102:(3): 281–91, discussion 426.
1242:Mikkelson D (27 July 2003).
660:) sold under the brand name
1184:Mitchell J, Rook A (1979).
856:dimethylallyl pyrophosphate
849:Dimethylallyl pyrophosphate
606:COc1c2c(ccc(=O)o2)cc3c1occ3
1959:
1392:Calcipotriol/betamethasone
786:Synthesis of umbelliferone
528:Chemical and physical data
1747:Furanocoumarin glycosides
1480:
1250:. Snopes Media Group Inc.
639:
614:
594:
254:
70:Consumer Drug Information
26:
1913:IARC Group 1 carcinogens
1289:Drugs used for psoriasis
840:Synthesis of methoxsalen
774:pathway, which produces
741:Heracleum mantegazzianum
1908:Photosensitizing agents
915:IARC Group 1 carcinogen
818:cinnamate 4-hydroxylase
1923:O-methylated coumarins
882:Risks and side effects
878:to yield methoxsalen.
851:
797:
1231:on 30 September 2016.
988:"AusPAR: Methoxsalen"
876:S-adenosyl methionine
847:
793:
747:Heracleum sphondylium
734:in the carrot family
280:-furobenzopyran-7-one
1835:Ethyl biscoumacetate
906:, and in rare cases
1168:Nielsen BE (1970).
927:John Howard Griffin
921:Society and culture
888:high blood pressure
800:Umbelliferone is a
682:cutaneous lymphomas
664:among others, is a
206:(Prescription only)
23:
1840:4-Hydroxycoumarins
1507:Never to phase III
1209:Dewick PM (2009).
1139:10.1038/ncponc0511
994:. 12 December 2019
965:. 13 December 2019
852:
798:
780:mevalonate pathway
700:. They consist of
273:-furochromen-7-one
1903:CYP3A4 inhibitors
1898:CYP1A2 inhibitors
1863:
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1195:978-0-88978-047-7
1131:Nature Publishing
864:psoralen synthase
725:, bishop's weed.
690:Fitzpatrick scale
651:
650:
585:Interactive image
478:CompTox Dashboard
214:
201:
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16:Chemical compound
1950:
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1018:nctr-crs.fda.gov
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952:
890:or a history of
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140:Extracorporeal,
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31:
24:
22:
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1928:Catechol ethers
1918:Furanocoumarins
1888:
1887:
1886:
1876:
1874:
1866:
1864:
1859:
1808:
1784:
1758:
1738:
1707:
1668:Furanocoumarins
1655:
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1512:
1497:Clinical trials
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953:
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842:
836:umbelliferone.
830:carboxylic acid
822:4-coumaric acid
806:L-phenylalanine
802:phenylpropanoid
788:
768:
760:furanocoumarins
717:
715:Natural sources
698:furanocoumarins
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230:Pharmacokinetic
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1724:Isopimpinellin
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1005:
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886:Patients with
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812:, followed by
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668:used to treat
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1850:Phenprocoumon
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1843:
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1838:
1836:
1833:
1831:
1828:
1826:
1825:Coumatetralyl
1823:
1821:
1820:Acenocoumarol
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1607:
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1600:
1597:
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1579:
1578:Umbelliferone
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1565:
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1187:
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1128:
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934:
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932:Black Like Me
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905:
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839:
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827:
826:umbellic acid
823:
819:
815:
814:hydroxylation
811:
810:cinnamic acid
807:
803:
796:
795:Umbelliferone
792:
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781:
777:
776:umbelliferone
773:
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511:ECHA InfoCard
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36:Clinical data
34:
30:
25:
1943:Plant toxins
1938:Orphan drugs
1728:
1712:O-Methylated
1587:O-Methylated
1439:
1387:Calcipotriol
1380:
1376:Fumaric acid
1359:
1247:
1237:
1229:the original
1219:
1210:
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1079:17 September
1077:. Retrieved
1072:
1063:
1053:17 September
1051:. Retrieved
1046:
1037:
1025:. Retrieved
1017:
1008:
998:17 September
996:. Retrieved
991:
967:. Retrieved
959:
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885:
853:
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769:
766:Biosynthesis
751:
745:
739:
738:, including
729:
727:
720:
718:
661:
657:
653:
652:
641:
458:NIAID ChemDB
277:
270:
238:Elimination
189:Legal status
183:Legal status
78:License data
1845:Hymecromone
1780:Imperatorin
1775:Bergamottin
1729:Methoxsalen
1703:Xanthotoxol
1660:Derivatives
1493:from market
1440:Methoxsalen
1435:Trioxysalen
1360:Methoxsalen
1355:Trioxysalen
1133:: 302–314.
758:) or other
686:ultraviolet
680:, and some
658:xanthotoxin
654:Methoxsalen
568: g·mol
517:100.005.516
427:CHEBI:18358
276:9-methoxy-7
269:9-methoxy-7
250:Identifiers
97:Methoxsalen
54:xanthotoxin
51:Other names
42:Trade names
21:Methoxsalen
1892:Categories
1804:Dicoumarol
1734:Trioxsalen
1623:Glycosides
1609:Scopoletin
1568:Aesculetin
1463:Etretinate
1408:Tazarotene
1402:Tacalcitol
1397:Calcitriol
1248:snopes.com
939:References
778:, and the
722:Ammi majus
666:medication
573:3D model (
561:Molar mass
387:U4VJ29L7BQ
358:ChemSpider
293:CAS Number
259:IUPAC name
1830:Ensaculin
1813:Synthetic
1797:Oligomers
1770:Auraptene
1719:Bergapten
1683:Angelicin
1676:Aglycones
1599:Herniarin
1560:Aglycones
1552:coumarins
1550:Types of
1503:Phase III
1491:Withdrawn
1468:Acitretin
1455:Retinoids
1445:Bergapten
1428:Psoralens
1382:vitamin D
1347:Psoralens
1337:Dithranol
1329:Antracens
969:25 August
904:dizziness
900:headaches
866:to yield
820:to yield
772:shikimate
756:bergapten
752:Heracleum
731:Heracleum
705:annulated
670:psoriasis
662:Oxsoralen
447:ChEMBL416
240:half-life
134:Routes of
108:Pregnancy
64:Drugs.com
1882:Medicine
1855:Warfarin
1693:Psoralen
1688:Marmesin
1646:Scopolin
1631:Aesculin
1594:Fraxetin
1421:Systemic
1319:Coal tar
1147:16757968
1108:20273299
1073:DailyMed
1047:DailyMed
956:"Uvadex"
908:insomnia
868:psoralen
860:marmesin
736:Apiaceae
702:coumarin
678:vitiligo
644:(verify)
338:DrugBank
302:298-81-7
245:~2 hours
149:ATC code
142:By mouth
110:category
92:DailyMed
1754:Apterin
1698:Vaginol
1641:Skimmin
1573:Ferujol
1301:Topical
1155:8441159
925:Author
834:lactone
566:216.192
534:Formula
347:DB00553
313:PubChem
221:Rx-only
218:WARNING
169: (
167:D05BA02
165:)
159: (
157:D05AD02
123: D
94::
1868:Portal
1636:Fraxin
1604:Osthol
1486:WHO-EM
1192:
1153:
1145:
1106:
1027:22 Oct
896:nausea
674:eczema
599:SMILES
467:001590
438:ChEMBL
407:D00139
215:
202:
90:
1369:Other
1151:S2CID
1129:(6).
963:(TGA)
892:liver
709:furan
707:with
619:InChI
575:JSmol
418:ChEBI
1308:Tars
1190:ISBN
1143:PMID
1104:PMID
1081:2021
1055:2021
1029:2023
1000:2021
971:2020
874:and
744:and
656:(or
398:KEGG
378:UNII
367:3971
327:4114
232:data
60:AHFS
1315:Tar
1293:D05
1135:doi
1022:FDA
816:by
483:EPA
317:CID
172:WHO
162:WHO
1894::
1499::
1317:/
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898:,
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672:,
542:12
211:US
204:S4
198:AU
119:AU
87:US
1870::
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1529:v
1404:)
1385:(
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1291:(
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1137::
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973:.
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554:4
551:O
548:8
545:H
539:C
485:)
481:(
278:H
271:H
213::
200::
175:)
121::
62:/
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