CAS 4449-51-8|Cyclopamine

Introduction：Basic information about CAS 4449-51-8|Cyclopamine, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Cyclopamine BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
5. Safety Information
6. Synonyms

Common Name	Cyclopamine
CAS Number	4449-51-8	Molecular Weight	411.620
Density	1.1±0.1 g/cm3	Boiling Point	550.8±50.0 °C at 760 mmHg
Molecular Formula	C₂₇H₄₁NO₂	Melting Point	236-238ºC
MSDS	/	Flash Point	286.9±30.1 °C

Names

Name	Cyclopamine
Synonym	More Synonyms

Cyclopamine BiologicalActivity

Description	Cyclopamine is a Hedgehog (Hh) pathway antagonist with an IC50 of 46 nM in the Hh cell assay.
Related Catalog	Signaling Pathways >>Stem Cell/Wnt >>HedgehogNatural Products >>SteroidsResearch Areas >>Cancer
Target	IC50: 46 nM (Hedgehog, in Hh cell assay)[1]
In Vitro	Treatment with small molecule Hh inhibitors such as HhAntag and the natural product Cyclopamine, both binding to Smo, induces tumor remission in a genetic mouse model of medulloblastoma[1]. Cyclopamine is a Hedgehog (Hh) pathway antagonist. Cyclopamine suppresses cell growth. Cyclopamine (3 μM) suppression of Hh pathway activity and growth in digestive tract tumour cell lines correlates with expression of PTCHmRNA[2]. Cyclopamine is a steroidal alkaloid that inhibits Hh signalling through direct interaction with Smo[3].
In Vivo	Cyclopamine causes durable regression of xenograft tumors. Tumors in Cyclopamine-treated animals, regress completely by 12 days[2]. Cyclopamine (1.2 mg) treatment blocks tumour formation of human pancreatic adenocarcinoma cells after transplantation into nude mice[3].
Cell Assay	Cells are cultured in triplicate in 96-well plates in assay media to which 5E1 monoclonal antibody, ShhNp and/or Cyclopamine (3 μM) are added at 0 h at concentrations indicated in the main text. Viable cell mass is determined by optical density measurements at 490 nm (OD490) at 2 and 4 days using the CellTiter96 colorimetric assay. Relative growth is calculated as OD (day 4)-OD (day 2)/OD (day 2)[2].
Animal Admin	Mice[3] A total of 0.1 mL Hanks’ balanced salt solution and matrigel (1:1) containing 2×106 cells is injected subcutaneously into CD-1 nude mice. Tumors are grown for 4 days to a minimum volume of 125 mm3; treatment is initiated simultaneously for all subjects. Mice are injected subcutaneously with vector alone (triolein:ethanol 4:1 v/v) or a Cyclopamine suspension (1.2 mg per mouse in triolein:ethanol 4:1 v/v) daily for 7 days. At the end of the treatment period, tumours are excised from mice, weighed and then fixed for 3 h at 4°C with 4% paraformaldehyde, embedded in paraffin wax and sectioned (6 µm). Apoptotic cells are identified by TUNEL using recombinant Tdt. Sections are then counterstained with eosin. Eight ×20-magnified fields from regions corresponding to the exterior, middle and interior of two control and two cyclopamine-treated tumours are chosen at random. We counted the number of TUNEL-positive nuclei manually. Haematoxylin/eosin staining is done.
References	[1]. Peukert S, et al. Identification and structure-activity relationships of ortho-biphenyl carboxamides as potent Smoothened antagonists inhibiting the Hedgehog signaling pathway. Bioorg Med Chem Lett, 2009, 19(2), 328-331. [2]. Berman DM, et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature, 2003, 425(6960), 846-851. [3]. Thayer SP, et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature, 2003, 425(6960), 851-856. [4]. Ma W, et al. Reduced Smoothened level rescued Aβ-induced memory deficits and neuronal inflammation in animal models of Alzheimer's disease. J Genet Genomics. 2018 May 20;45(5):237-246.

Chemical & Physical Properties

Density	1.1±0.1 g/cm3
Boiling Point	550.8±50.0 °C at 760 mmHg
Melting Point	236-238ºC
Molecular Formula	C₂₇H₄₁NO₂
Molecular Weight	411.620
Flash Point	286.9±30.1 °C
Exact Mass	411.313721
PSA	41.49000
LogP	5.44
Vapour Pressure	0.0±3.4 mmHg at 25°C
Index of Refraction	1.583
InChIKey	QASFUMOKHFSJGL-LAFRSMQTSA-N
SMILES	CC1=C2CC3C(CC=C4CC(O)CCC43C)C2CCC12OC1CC(C)CNC1C2C
Storage condition	2-8°C
Stability	Store in Freezer at - 20°C
Water Solubility	DMSO: soluble

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: GY0750000

CHEMICAL NAME :: Cyclopamine

CAS REGISTRY NUMBER :: 4449-51-8

LAST UPDATED :: 199712

DATA ITEMS CITED :: 11

MOLECULAR FORMULA :: C27-H41-N-O2

MOLECULAR WEIGHT :: 411.69

WISWESSER LINE NOTATION :: L D6 B566 FX DU LUTJ A1 E1 OQ F-& CT56 BOX FMTJ D1 H1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 180 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 149,302,1975

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - hamster

DOSE/DURATION :: 170 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 149,302,1975 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 120 mg/kg

SEX/DURATION :: female 6-9 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :: LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 1,1187,1973

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 300 mg/kg

SEX/DURATION :: female 10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 29(2),22A,1984

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 44500 ug/kg

SEX/DURATION :: female 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 136,1174,1971

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 116 mg/kg

SEX/DURATION :: female 7-8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - eye/ear

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 136,1174,1971

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 250 mg/kg

SEX/DURATION :: female 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 149,302,1975

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 170 mg/kg

SEX/DURATION :: female 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 149,302,1975

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 54546 ug/kg

SEX/DURATION :: female 30-31 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 142,1287,1973

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 30 mg/kg

SEX/DURATION :: female 14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 192,153,1989 *** REVIEWS *** TOXICOLOGY REVIEW AEMBAP Advances in Experimental Medicine and Biology. (Plenum Pub. Corp., 233 Spring St., New York, NY 10013) V.1- 1967- Volume(issue)/page/year: 27,107,1972

Safety Information

Hazard Codes	Xi: Irritant;
Safety Phrases	22-24/25
WGK Germany	3
RTECS	GY0750000

Synonyms

11-DEOXYJERVINE

alkaloidv

Spiro[9H-benzo[a]fluorene-9,2'(3'H)-furo[3,2-b]pyridin]-3-ol, 1,2,3,3'a,4,4',5',6,6',6a,6b,7,7',7'a,8,11,11a,11b-octadecahydro-3',6',10,11b-tetramethyl-, (3S,3'R,3a'S,6'S,6aS,6bS,7a'R,9R,11aS,11bR)-

deoxojervine

11-Desoxo-jervin

Veratraman-3-ol, 17,23-epoxy-, (3β,23β)-

Cyclopamine

(3β,22S,23R)-17,23-Epoxyveratraman-3-ol

Spiro(9H-benzo(a)fluorene-9,2'(3'H)-furo(3,2-b)pyridin)-3-ol, 1,2,3,3'a,4,4',5',6,6',6a,6b,7,7',7'a,8,11,11a,11b-octadecahydro-3',6',10,11b-tetramethyl-, (2'R,3S,3'R,3'aS,6'S,6aS,6bS,7'aR,11aS,11bR)-

11-deoxojervine

MFCD01735266

(3β,17β,22S,23R)-17,23-Epoxyveratraman-3-ol

11-deoxo-jervin

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