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Jervine

Jervine structure

CAS No:
469-59-0
Formula:
C27H39NO3
Chemical Name:
Jervine
Synonyms:
Spiro[9H-benzo[a]fluorene-9,2′(3′H)-furo[3,2-b]pyridin]-11(1H)-one,2,3,3′a,4,4′,5′,6,6′,6a,6b,7,7′,7′a,8,11a,11b-hexadecahydro-3-hydroxy-3′,6′,10,11b-tetramethyl-,(2′R,3S,3′R,3′aS,6′S,6aS,6bS,7′aR,11aS,11bR)-;Jervine;Veratraman-11-one,17,23-epoxy-3-hydroxy-,(3β,23β)-;(2′R,3S,3′R,3′aS,6′S,6aS,6bS,7′aR,11aS,11bR)-2,3,3′a,4,4′,5′,6,6′,6a,6b,7,7′,7′a,8,11a,11b-Hexadecahydro-3-hydroxy-3′,6′,10,11b-tetramethylspiro[9H-benzo[a]fluorene-9,2′(3′H)-furo[3,2-b]pyridin]-11(1H)-one;Jervin;Spiro[9H-benzo[a]fluorene-9,2′(3′H)-furo[3,2-b]pyridin]-11(1H)-one,2,3,3′a,4,4′,5′,6,6′,6a,6b,7,7′,7′a,8,11a,11b-hexadecahydro-3-hydroxy-3′,6′,10,11b-tetramethyl-,[3S-(3α,6aα,6bβ,9α(3′S*,3′aR*,6′R*,7′aS*),11aβ,11bα)]-;NSC 23898;NSC 7520;30937-13-4
Categories:
Pharmaceutical Intermediates > Bulk Drug Intermediates

Description

Jervine(11-Ketocyclopamine) is a naturally occuring steroidal alkaloid that causes cyclopia by blocking sonic hedgehog(Shh) signaling; Jervine is an inhibitor of Smo.IC50 value:Target: sonic hedgehog is derived from the Veratrum plant species. It is a close structural analog of cyclopamine which specifically inhibits the hedgehog (Hh) pathway by interaction with the hedgehog signaling protein Smo. Jervine can be used to induce abnormal morphogenesis in a number of experimental models. Je

Jervine is a member of piperidines.

Jervine Basic Attributes

Molecular Weight：

425.613

Exact Mass：

425.60

EC Number：

207-417-9

UNII：

19V3ECX465

NSC Number：

23898|7520

Color/Form：

NEEDLES FROM METHANOL + WATER

HScode：

29349990

Characteristics

PSA：

58.6

XLogP3：

2.9

Density：

1.2±0.1 g/cm3

Melting Point：

243.5-244.5 °C

Boiling Point：

592°C at 760 mmHg

Flash Point：

311.8±30.1 °C

Refractive Index：

1.591

Water Solubility：

SOL IN ALCOHOL, ACETONE, CHLOROFORM

Storage Conditions：

-20ºC

Vapor Pressure：

1.75E-16mmHg at 25°C

Toxicity：

LD50 i.v. in mice: 9.3 mg/kg (Krayer); LD50 s.c. in male mice: 29 mg/kg (Tanaka)

Specific rotation：

SPECIFIC OPTICAL ROTATION (ETHANOL): -150 DEG @ 20 °C/D; -167.6 DEG @ 20 °C/D (CHLOROFORM); MAX ABSORPTION: 250, 360 NM (E= 15,000, 60)

Safety Information

Packing level：

Ⅲ

Transport codes：

2811

wgk germany：

hazard class code：

6.1

RTECS Number：

WG9700000

Marks：

Xn: Harmful;

Stability/Shelf Life：

Store in Freezer at - 20°C

Precautionary statement(s)：

P301 + P310

Hazard Statements：

H301

Toxicity

Natural Pollution Sources：

STEROIDAL ALKALOID FOUND IN VERATRUM GRANDIFLORUM (MAXIM) LOES F, V ALBUM L, V VIRIDE SOL, LILIACEAE: SAITO BULL CHEM SOC JAPAN 9, 15 (1934), CA 28, 2463 (1934); POETHKE, ARCH PHARM 275, 357, 571 (1937); 276, 170 (1938); 282, 56 (1944); SEIFERLE ET AL, J ECON ENTOMOL 35, 35 (1942); JACOBS, CRAIG, J BIOL CHEM 160, 555 (1945).

Drug Information

Metabolism/Metabolites：

Malformations in hatched chicks were produced by direct application of 1-2 mg of cyclopamine to the embryonic shield of windowed chicken eggs. This showed that maternal metabolic alteration of cyclopamine was not necessary. /PRC: Cyclopamine is a member of the jerveratum group as is jervine/. /CYCLOPAMINE/|INCORPORATION OF ACETATE-1-(14)C, CHOLESTEROL-4-(14)C, & OF CHOLESTEROL-26-(14)C INTO JERVINE & VERATRAMINE GAVE A LABELING PATTERN CONSISTENT WITH THE HYPOTHESIS THAT A KEY INTERMEDIATE DERIVED FROM EPIRUBIJERVINE WAS CONVERTED INTO THE C-NOR-D-HOMOSTEROIDAL ALKALOIDS (JERVINE & VERATRAMINE) BY SEPARATE PATHWAYS IN VERATRUM GRANDIFLORUM.

Mechanism of Action：

Cyclopamine (1) and jervine (2) are potent teratogens that inhibit Sonic hedgehog (Shh) signaling during gastrulation-stage embryonic development, producing cyclopia and holoprosencephaly.|A NUMBER OF VERATRUM ALKALOIDS WERE TESTED IN PREGNANT SHEEP FOR TERATOGENICITY. THE COMPOUNDS JERVINE, CYCLOPAMINE...AND CYCLOPOSINE...PRODUCED DEFORMITIES SIMILAR TO NATURAL CASES. THE 3 TERATOGENIC COMPOUNDS ARE CLOSELY RELATED STEROIDAL FURANOPIPERIDINES, BUT CYCLOPAMINE IS THE TERATOGEN OF NATURAL IMPORTANCE BECAUSE OF PLANT CONCN. CLOSELY RELATED COMPD DEVOID OF THE FURAN RING DID NOT PRODUCE CYCLOPIA IN SHEEP, SUGGESTING THAT AN INTACT FURAN RING WAS REQUIRED FOR ACTIVITY, PERHAPS CONFERRING SOME ESSENTIAL CONFIGURATION ON THE MOLECULE.

Human Toxicity Excerpts：

Several species of the Veratrum genus are associated with toxicity in humans and animals. The principal toxins are steroid alkaloids; some have a modified steroid template, whereas others differ in their esterified acid moieties. These alkaloids act by increasing the permeability of the sodium channels of nerve cells, causing them to fire continuously. Increased stimulation, associated with the vagal nerve results in a reflex that causes the triad of responses known as the Bezold-Jarisch reflex: hypotension, bradycardia and apnea. Clinically, various Veratrum extracts were marketed for use as antihypertensive drugs, but because of their narrow therapeutic index were withdrawn from the market. Following the ingestion of Veratrum alkaloids, expected signs and symptoms include vomiting and abdominal pain, followed by cardiovascular effects such as bradycardia, hypotension and cardiac conduction abnormalities and death. Similar symptoms arise in other mammalian species ingesting these alkaloids; teratogenic effects may occur to the fetuses of animals that have grazed on Veratrum californicum. Treatment consists of supportive care, with an emphasis on hemodynamic stability with fluid replacement, atropine and vasopressors. The onset of symptoms occurs between 30 minutes and 4 hours, and the duration of the illness can range from 1 to 10 days; however, with prompt supportive care, patients typically make a full recovery within 24 hours.

MeSH Entry Terms：

jervine

Jervine Use and Manufacturing

Methods of Manufacturing

TOTAL SYNTHESIS: KUTNEY ET AL, CAN J CHEM 53, 1796 (1975).

Uses

Has antibacterial properties. Jervine demonstrates teratogenic properties. It is the starting material for C-nor-D-homosteroids. Jervine induces holoprosencephaly and blocks endogenous Sonic hedgehog signaling

Manufacturing Info：

An alkamine isolated from Veratrum album.

Analytic Methods：

A competitive inhibition enzyme-linked immunosorbent assay (ELISA) to detect and measure cyclopamine (1) and jervine (2) was developed using polyclonal antibodies produced in ewes. The limits of detection of the assay were 90.0 and 22.7 pg for cyclopamine (1) and jervine (2), respectively. This assay was used for the detection and measurement of cyclopamine (1) spiked into sheep blood. The simple extraction-ELISA methods developed in this study demonstrate the potential of using these techniques for the rapid screening of biological samples to detect the presence and concentration of cyclopamine (1) and jervine (2) and will be beneficial to pharmacological studies and livestock diagnostics.|High-pressure liquid chromatography of steroidal alkaloids including jervine.|Thin layer chromatography of steroidal alkaloids including jervine.

Computed Properties

Molecular Weight:425.6
XLogP3:2.9
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Exact Mass:425.29299411
Monoisotopic Mass:425.29299411
Topological Polar Surface Area:58.6
Heavy Atom Count:31
Complexity:876
Defined Atom Stereocenter Count:10
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes

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