In MKN45 cells, α-amanitin lowers TAF15 mRNA and protein levels and prevents RNAPII from acting on TAF15 mRNA [2]. At doses of 100, 10, 1, 0.1, and 0.01 μg/mL, α-amanitin decreased cell viability by 14%, 21%, 41%, 44%, and 50%, respectively. At 36 hours, the α-Amanitin's LD50 was determined to be 1 μg/mL. At a concentration of 1 μg/mL, α-Amanitin considerably raised the total amount of intracellular protein at 24 hours in comparison to the control [3]. The cumulus cell gap junction genes (Gja1, Gja4, and Gjc1), as well as FSHr and LHr, are much less expressed when α-amanitin is present [4].

After intravenous administration, the α-Amanitin's LD50 in BALB/c mice was 0.327 mg/kg. Serum levels of WBC, RBC, and HGB dramatically decreased twelve hours after α-Amanitin was injected into the tail vein, whereas serum levels of BUN and Crea significantly increased. Certain genes (Hsp90b1, Irx4, etc.) are inhibited by α-amanitin, and the protein it encodes controls the activity of RNA polymerase II. Certain transcription-related proteins, including as Nmi and Trpc5, are down-regulated by α-amanitin [1]. α-Amanitin exhibits strong DTC inhibition properties. Whereas the body weight of mice receiving intraperitoneal injection of MKN45 cells continued to drop, the body weight of mice injected with cells treated with α-Amanitin (0.4 mg/kg, ip) remained stable [2].

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Amatoxins are water soluble, heat stable polypeptides found in Amanita (most often Amanita phalloides ), Galerina and some Lepiota species. The main toxin from the species A. phalloides is alpha-amanitin, a cyclic octapeptide. It is a potent inhibitor of RNA polymerases that blocks the production of mRNA and protein synthesis in liver and kidney cells. In one case, an infant developed elevated liver enzymes after nursing once 11.5 hours after maternal ingestion of Amanita phalloides. However, two recent, well-documented cases found no adverse effects in breastfed infants and no amatoxin in the milk. Nevertheless, mothers suspected of having Amanita mushroom poisoning probably should not breastfeed until they have recovered or toxicologic screening of the breastmilk has ruled out toxicity.
◉ Effects in Breastfed Infants
In Germany, a 20-year-old nursing mother ate a meal of solely mushrooms identified in the report as green tuberous mushroom (Amanita phalloides). The next morning around 11.5 hours after mushroom ingestion, she nursed her 10-week-old infant who weighed 5 kg. The meal consisted of 80 to 100 mL of breastmilk and the same amount of ready-to-use infant formula (Milasan-Neu). At this time the mother already had symptoms of intoxication (vomiting and diarrhea). Because of the deterioration in her condition she was unable to continue breastfeeding the child, so the child received only formula thereafter. After the mother was admitted to the hospital for Amanita phalloides poisoning and had ASAT and ALAT values of 10,000 and 40,000, respectively (normal values about 500-550). The infant was placed under inpatient observation at children’s hospital. The infant’s relatives noticed nothing unusual about the child and the clinical admission examination revealed no visible evidence of a hepatic, cerebral or hematological disease. Six days after maternal mushroom ingestion, the infant’s laboratory values (electrolytes, serum electrophoresis, bilirubin, gamma-GT, alkaline phosphatase, creatinine, blood sugar, urine status, PTT, and PT [Quick test]) were normal except for ASAT and ALAT, which were about double the normal value. These values slowly decreased and became normal at about day 40 after ingestion.
A 32-year-old mother shared a meal of foraged mushrooms (Amanita bisporigera), and developed symptoms 15 hours post-ingestion. She presented to the emergency department 29 hours post-ingestion and was found to have markedly elevated liver enzymes. Her 4 month-old-daughter had breastfed 4 hours post-ingestion. The asymptomatic infant was evaluated 48 hours after breastfeeding and discharged from the emergency department with no evidence of hepatotoxicity.
A 33-year-old woman picked about 200 mushrooms in a forest in France. She cooked and ate some of them, and developed nausea, vomiting and diarrhea 11 hours post-ingestion. She was admitted to the hospital for treatment and had elevated liver enzymes. She had breastfed her 5-month-old daughter 3 times a day over the 36 hours after mushroom ingestion. Her daughter was hospitalized, but did not present any symptoms, nor any biological disturbance.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Interactions
...PHARMACOLOGICAL AGENTS.../HAVE/ BEEN REPORTED TO PROTECT MICE AGAINST LETHAL DOSES OF PHALLOTOXINS & AMATOXINS /INCLUDING THE AMANITINS/. THE LIST INCLUDES HIGH DOSES OF PENICILLIN, CHLORAMPHENICOL, PHENYLBUTAZONE, & MANY OTHERS... NONE OF THESE ANTIDOTES HAS RECEIVED AN ADEQUATE CLINICAL TRIAL & SO NONE CAN BE RECOMMENDED TODAY. /AMANITINS/
RNA SYNTHESIS IN HELA NUCLEI WAS STIMULATED BY METHYLMERCURY. THIS STIMULATION IS SPECIFIC FOR ALPHA-AMANITIN-SENSITIVE RNA SYNTHESIS (CATALYZED BY RNA POLYMERASE); IN CONTRAST, ALPHA-AMANITIN-RESISTANT SYNTHESIS (CATALYZED BY RNA POLYMERASES I & III) WAS INHIBITED.

[1]. Pathological effects of the mushroom toxin alpha-amanitin on BALB/c mice. Peptides. 2006 Dec;27(12):3047-3052.

[2]. α-Amanitin Restrains Cancer Relapse from Drug-Tolerant Cell Subpopulations via TAF15. Sci Rep. 2016 May 16;6:25895.

[3]. Evaluation and comparison of alpha- and beta-amanitin toxicity on MCF-7 cell line. Turk J Med Sci. 2014;44(5):728-32.

[4]. RNA Polymerase II Inhibitor, α-Amanitin, Affects Gene Expression for Gap Junctions and Metabolic Capabilities of Cumulus Cells, but Not Oocyte, during in vitro Mouse Oocyte Maturation. Dev Reprod. 2013 Mar;17(1):63-72.

alpha-Amanitin has been reported in Amanita suballiacea, Amanita phalloides, and other organisms with data available.
A cyclic octapeptide with a thioether bridge between the cystine and tryptophan. It inhibits RNA POLYMERASE II. Poisoning may require LIVER TRANSPLANTATION.

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Mechanism of Action
/IN COMPARISON WITH THE PHALLOTOXINS/...THE LONG DELAYED HEPATOTOXIC RESPONSE SEEN IN HUMAN POISONINGS...IS MORE LIKELY DUE TO...ALPHA-, BETA-, & GAMMA-AMANITIN, ESPECIALLY THE ALPHA COMPONENT. THESE SO-CALLED AMATOXINS...ARE MORE TOXIC THAN THE PHALLOTOXINS, &, UNLIKE THE LATTER, THEY DAMAGE THE NUCLEOLUS & LATER THE NUCLEUS OF LIVER CELLS.

C₃₉H₅₄N₁₀O₁₄S

918.97

918.354

23109-05-9

441541

White to yellow solid powder

1.57 g/cm3

1622.2ºC at 760 mmHg

254-255ºC(lit.)

934.9ºC

1.694

-4.4

13

15

7

64

1840

10

CC[C@H](C)[C@H]1C(=O)NCC(=O)N[C@H]2CS(=O)C3=C(C[C@@H](C(=O)NCC(=O)N1)NC(=O)[C@@H](NC(=O)[C@@H]4C[C@H](CN4C(=O)[C@@H](NC2=O)CC(=O)N)O)[C@@H](C)[C@H](CO)O)C5=C(N3)C=C(C=C5)O

CIORWBWIBBPXCG-JAXJKTSHSA-N

InChI=1S/C39H54N10O14S/c1-4-16(2)31-36(60)42-11-29(55)43-25-15-64(63)38-21(20-6-5-18(51)7-22(20)46-38)9-23(33(57)41-12-30(56)47-31)44-37(61)32(17(3)27(53)14-50)48-35(59)26-8-19(52)13-49(26)39(62)24(10-28(40)54)45-34(25)58/h5-7,16-17,19,23-27,31-32,46,50-53H,4,8-15H2,1-3H3,(H2,40,54)(H,41,57)(H,42,60)(H,43,55)(H,44,61)(H,45,58)(H,47,56)(H,48,59)/t16-,17-,19+,23-,24-,25-,26-,27-,31-,32-,64?/m0/s1

2-[(1R,4S,8R,10S,13S,16S,34S)-34-[(2S)-butan-2-yl]-13-[(2R,3R)-3,4-dihydroxybutan-2-yl]-8,22-dihydroxy-2,5,11,14,27,30,33,36,39-nonaoxo-27λ4-thia-3,6,12,15,25,29,32,35,38-nonazapentacyclo[14.12.11.06,10.018,26.019,24]nonatriaconta-18(26),19(24),20,22-tetraen-4-yl]acetamide

α-Amanitin α-Amatoxin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). This product is not stable in solution, please use freshly prepared working solution for optimal results.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~100 mg/mL (~108.82 mM)

Solubility in Formulation 1: 25 mg/mL (27.20 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)