Mithramycin A

Mithramycin A structure	Common Name	Mithramycin A
CAS Number	18378-89-7	Molecular Weight	1085.145
Density	1.5±0.1 g/cm3	Boiling Point	1169.8±65.0 °C at 760 mmHg
Molecular Formula	C₅₂H₇₆O₂₄	Melting Point	180-183ºC
MSDS	Chinese USA	Flash Point	327.4±27.8 °C
Symbol	GHS07	Signal Word	Warning

Name	mithramycin
Synonym	More Synonyms

Description	Plicamycin is a selective specificity protein 1 (Sp1) inhibitor. Plicamycin inhibits the growth of various cancers by decreasing Sp1 protein.
Related Catalog	Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis Research Areas >> Cancer
Target	Sp1 transcription factor[1]
In Vitro	Sp1 is a zinc-finger transcription factor that regulates multiple cellular functions and promotes tumor progression by controlling expression of genes involved in cell cycle, apoptosis and DNA damage. Sp1 binds to GC-rich motifs of promoters and interacts with components of the general transcriptional machinery and co-activator complexes of multiple signaling pathways. Plicamycin (Mith) decreases Sp1 protein by inducing proteasome-dependent degradation, thereby suppressing cervical cancer growth through a DR5/caspase-8/Bid signaling pathway. To assess the antiproliferative effects of Plicamycin on cervical cancer cells, two cervical cancer cell lines with different genetic backgrounds are grown with or without treatment with Plicamycin at different concentrations. Plicamycin inhibits HEp-2 and KB cell growth in a concentration-dependent manner after 48 h. Apoptotic cell death is qualitatively estimated by DAPI staining for nuclear condensation and fragmentation. Plicamycin leads to significant DNA fragmentation compared to untreated controls[1].
In Vivo	The antitumorigenic activity of Plicamycin (0.2 mg/kg/day) is determined in a xenograft model and observed reduction in tumor volume and weight. No significant mouse body weight loss is observed in Plicamycin-treatment groups, indicating that Plicamycin-associated toxicity is minimal. Plicamycin also increases TUNEL-positive cells in tumor xenografts. No notable intergroup differences are observed among organs, indicating no marked signs of systemic toxicity at the Plicamycin dose used in this study[1].
Cell Assay	HEp-2 cells and KB cells are cultured in DMEM 100 U/mL each of Penicillin and Streptomycin and 10% FBS for HEp-2 cells and 5% FBS for KB in a humidified atmosphere containing 5% CO2 at 37°C. Equal numbers of cells are seeded and allowed to attach. At 50-60% confluence, cells are treated with DMSO or indicated concentrations of Plicamycin (50, 100, and 200 nM for HEp-2 cells; 20, 40, and 80 nM for KB cells). Cell viability is determined using CellTiter 96 Aqueous One Solution Cell Proliferation Assay Kits. In brief, cells are seeded in 96-well plates and incubated with Plicamycin. After treatment, 30 µL MTS solution is added to each well and cells are incubated for 2 h at 37°C. MTS solution is analyzed using a microplate reader at 490 nm and 690 nm[1].
Animal Admin	Mice[1] Female nude mice are used. KB cells are suspended in sterile PBS and injected subcutaneously into the right flank of mice. Mice are randomized into two groups containing five mice each and treated with 0.2 mg/kg/day of Plicamycin (i.p.) three times per week for 29 days. Control mice receive an equal volume of vehicle. After 29 days, bodies, organs and tumors are weighed and tumor volumes determined. Tumors are measured[1].
References	[1]. Choi ES, et al. Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer. Sci Rep. 2014 Nov 24;4:7162.

Density	1.5±0.1 g/cm3
Boiling Point	1169.8±65.0 °C at 760 mmHg
Melting Point	180-183ºC
Molecular Formula	C₅₂H₇₆O₂₄
Molecular Weight	1085.145
Flash Point	327.4±27.8 °C
Exact Mass	1084.472656
PSA	358.20000
LogP	1.29
Vapour Pressure	0.0±0.3 mmHg at 25°C
Index of Refraction	1.640

Name:	Mithramycin 90% (HPLC) Material Safety Data Sheet
Synonym:	Aureolic Acid; Plicamycin
CAS:	18378-89-7

Section 1 - Chemical Product MSDS Name:Mithramycin 90% (HPLC) Material Safety Data Sheet
Synonym:Aureolic Acid; Plicamycin

Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
18378-89-7	Plicamycin	90	unlisted

Hazard Symbols: T
Risk Phrases: 23/24/25

Section 3 - HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW
Toxic by inhalation, in contact with skin and if swallowed.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation.
Ingestion:
May cause irritation of the digestive tract. Moderately toxic to humans by ingestion. The toxicological properties of this substance have not been fully investigated. May cause anemia, leukopenia (reduction in the number of white blood cells in the blood), and thrombocytopenia.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
No information found.

Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse.
Ingestion:
Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:

Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
Extinguishing Media:
Use agent most appropriate to extinguish fire. Use water spray, dry chemical, carbon dioxide, or appropriate foam.

Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Use with adequate ventilation. Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances. Keep refrigerated. (Store below 4C/39F.)

Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 18378-89-7: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use.

Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Powder
Color: yellow crystalline powder
Odor: none reported
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 180.00 - 183.00 deg C
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water: soluble in water
Specific Gravity/Density:
Molecular Formula: C52H76O24
Molecular Weight: 1085.16

Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, dust generation, excess heat, strong oxidants.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, irritating and toxic fumes and gases, carbon dioxide.
Hazardous Polymerization: Has not been reported

Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 18378-89-7: PZ2800000 LD50/LC50:
CAS# 18378-89-7: Oral, mouse: LD50 = 500 mg/kg.
TDLo -Oral, Human: 50 Carcinogenicity:
Plicamycin - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

Section 12 - ECOLOGICAL INFORMATION

Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

Section 14 - TRANSPORT INFORMATION

IATA
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.*
Hazard Class: 6.1
UN Number: 2811
Packing Group: III
IMO
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.
Hazard Class: 6.1
UN Number: 2811
Packing Group: III
RID/ADR
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.
Hazard Class: 6.1
UN Number: 2811
Packing group: III

Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: T
Risk Phrases:
R 23/24/25 Toxic by inhalation, in contact with skin
and if swallowed.
Safety Phrases:
S 28A After contact with skin, wash immediately with
plenty of water.
S 36/37/39 Wear suitable protective clothing, gloves
and eye/face protection.
S 37 Wear suitable gloves.
S 38 In case of insufficient ventilation, wear
suitable respiratory equipment.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 18378-89-7: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 18378-89-7 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 18378-89-7 is not listed on the TSCA inventory.
It is for research and development use only.

SECTION 16 - ADDITIONAL INFORMATION
N/A

CHEMICAL IDENTIFICATION

RTECS NUMBER :: PZ2800000

CHEMICAL NAME :: Mithramycin

CAS REGISTRY NUMBER :: 18378-89-7

LAST UPDATED :: 199609

DATA ITEMS CITED :: 27

MOLECULAR FORMULA :: C52-H76-O24

MOLECULAR WEIGHT :: 1085.28

WISWESSER LINE NOTATION :: L C666 DVT&&J BQ FYO1&VYQYQ1 M1 NQ LO- BT6OTJ EQ F1 DO- BT6OTJ DQ EQ F1&& EO- BT6OTJ EQ F1 DO

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 50 ug/kg/5D

TOXIC EFFECTS :: Blood - thrombocytopenia

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2500 ug/kg

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

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3100 ug/kg

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

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1741 ug/kg

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

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 500 mg/kg

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

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1090 ug/kg

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

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 2810 ug/kg

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

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 350 ug/kg

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

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 2 mg/kg

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

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 250 ug/kg

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

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 250 ug/kg

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 2400 mg/kg/4W-I

TOXIC EFFECTS :: Liver - change in gall bladder structure or function Blood - hemorrhage Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 2400 mg/kg/4W-I

TOXIC EFFECTS :: Blood - hemorrhage Blood - other changes Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 2 mg/kg

SEX/DURATION :: female 11 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

MUTATION DATA

TEST SYSTEM :: Rodent - hamster

DOSE/DURATION :: 1250 ug/kg/5D (Continuous)

REFERENCE :: ENMUDM Environmental Mutagenesis. (New York, NY) V.1-9, 1979-87. For publisher information, see EMMUEG. Volume(issue)/page/year: 4,231,1982 *** REVIEWS *** TOXICOLOGY REVIEW 32XPAD "Teratology," Berry, C.L., and D.E. Poswillo, eds., New York, Springer, 1975 Volume(issue)/page/year: -,49,1975 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3731 No. of Facilities: 290 (estimated) No. of Industries: 1 No. of Occupations: 8 No. of Employees: 6594 (estimated) No. of Female Employees: 2796 (estimated)

Symbol	GHS07
Signal Word	Warning
Hazard Statements	H302
Personal Protective Equipment	dust mask type N95 (US);Eyeshields;Faceshields;Gloves
Hazard Codes	Xn: Harmful;
Risk Phrases	R22
Safety Phrases	45-38-36/37/39-28A-22
RIDADR	UN 3249
WGK Germany	3
RTECS	PZ2800000
Packaging Group	III
Hazard Class	6.1(b)

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Antibiotic LA-7017

D-threo-2-Pentulose, 5-deoxy-1-C-[(2S,3S)-7-[[2,6-dideoxy-3-O-(2,6-dideoxy-β-D-arabino-hexopyranosyl)-β-D-lyxo-hexopyranosyl]oxy]-3-[[O-2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl-(1->3)-O-2,6-dideoxy-β-D-arabino-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl]oxy]-1,2,3,4-tetrahydro-5,10-dihydroxy-6-methyl-4-oxo-2-anthracenyl]-1-O-methyl-, (1S)-

aurlelicacid

MFCD00135618

EINECS 232-455-8

MITHRAMYCIN

Mithramycin A From Streptomyces Argillaceus

aurelicacid

(1S)-5-Deoxy-1-C-[(2S,3S)-7-{[2,6-dideoxy-3-O-(2,6-dideoxy-β-D-arabino-hexopyranosyl)-β-D-lyxo-hexopyranosyl]oxy}-3-{[2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl]oxy}-5,10-dihydroxy-6-methyl-4-oxo-1,2,3,4-tetrahydroanthracen-2-yl]-1-O-methyl-D-xylulose

(1S)-5-Deoxy-1-C-[(2R,3S)-7-{[2,6-dideoxy-3-O-(2,6-dideoxy-β-D-arabino-hexopyranosyl)-β-D-lyxo-hexopyranosyl]oxy}-3-{[2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl]oxy}-5,10-dihydroxy-6-methyl-4-oxo-1,2,3,4-tetrahydroanthracen-2-yl]-1-O-methyl-D-xylulose

PlicatoMycin

a-2371

D-threo-2-Pentulose, 5-deoxy-1-C-[(3S)-7-[[2,6-dideoxy-3-O-(2,6-dideoxy-β-D-arabino-hexopyranosyl)-β-D-lyxo-hexopyranosyl]oxy]-3-[[O-2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl-(1->3)-O-2,6 -dideoxy-β-D-arabino-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl]oxy]-1,2,3,4-tetrahydro-5,10-dihydroxy-6-methyl-4-oxo-2-anthracenyl]-1-O-methyl-, (1S)-

mitramycin

(1S)-5-Deoxy-1-C-[(3S)-7-{[2,6-dideoxy-3-O-(2,6-dideoxy-β-D-arabino-hexopyranosyl)-β-D-lyxo-hexopyranosyl]oxy}-3-{[2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arab ino-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl]oxy}-5,10-dihydroxy-6-methyl-4-oxo-1,2,3,4-tetrahydro-2-anthracenyl]-1-O-methyl-D-xylulose

(1S)-5-Deoxy-1-C-[(2R,3S)-7-{[2,6-dideoxy-3-O-(2,6-dideoxy-β-D-arabino-hexopyranosyl)-β-D-lyxo-hexopyranosyl]oxy}-3-{[2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl]oxy}-5,10-dihydroxy-6-methyl-4-oxo-1,2,3,4-tetrahydro-2-anthracenyl]-1-O-methyl-D-xylulose

pa144

AURLELIC ACID

Aurelic acid

PLICAMYCIN

MITHRACIN

Mithramycin A,(1S)-5-Deoxy-1-C-[(2S,3S)-7-[[2,6-dideoxy-3-O-(2,6-dideoxy-β-D-arabino-hexopyranosyl)-β-D-arabino-hexopyranosyl]oxy]-3-[(O-2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl-(1.fwdarw.3)-O-2,6-dideoxy-β-D-lyxo-hexopyranosyl-(1.fwdarw.3)-2,6-dideo

aureolic acid

Mithramycin A

Mithramycin A

Use of Mithramycin A

Names

Mithramycin A Biological Activity

Chemical & Physical Properties

MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

MUTATION DATA

Safety Information

Articles27

Synonyms