Name: γ-Amanitin
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

(1R,4S,8R,10S,13S,16S,34S)-4-(2-Amino-2-oxoethyl)-34-[(2S)-2-butanyl]-8,22-dihydroxy-13-[(2R,3S)-3-hydroxy-2-butanyl]-2,5,11,14,30,33,36,39-octaoxo-27-thionia-3,6,12,15,25,29,32,35,38-nonaazapentacyclo[14.12.11.06,10.018,26.019,24]nonatriaconta-18(26),19,21,23-tetraen-27-olate

IUPAC Name

2-[(1R,4S,8R,10S,13S,16S,34S)-34-[(2S)-butan-2-yl]-8,22-dihydroxy-13-[(2R,3S)-3-hydroxybutan-2-yl]-2,5,11,14,27,30,33,36,39-nonaoxo-27lambda4-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

Canonical SMILES

CCC(C)C1C(=O)NCC(=O)NC2CS(=O)C3=C(CC(C(=O)NCC(=O)N1)NC(=O)C(NC(=O)C4CC(CN4C(=O)C(NC2=O)CC(=O)N)O)C(C)C(C)O)C5=C(N3)C=C(C=C5)O

InChI

InChI=1S/C39H54N10O13S/c1-5-16(2)31-36(59)42-12-29(54)43-26-15-63(62)38-22(21-7-6-19(51)8-23(21)46-38)10-24(33(56)41-13-30(55)47-31)44-37(60)32(17(3)18(4)50)48-35(58)27-9-20(52)14-49(27)39(61)25(11-28(40)53)45-34(26)57/h6-8,16-18,20,24-27,31-32,46,50-52H,5,9-15H2,1-4H3,(H2,40,53)(H,41,56)(H,42,59)(H,43,54)(H,44,60)(H,45,57)(H,47,55)(H,48,58)/t16-,17-,18-,20+,24-,25-,26-,27-,31-,32-,63?/m0/s1

InChIKey

WVHGJJRMKGDTEC-ZUROAWGWSA-N

Density

1.5±0.1 g/cm3

Solubility

Soluble in DMSO

Flash Point

901.2±34.3 °C

Index Of Refraction

1.684

PSA

405.28000

Vapor Pressure

0.0±0.3 mmHg at 25°C

Appearance

White to Off-white Powder

Shelf Life

≥ 2 years

Shipping

Room temperature, or blue ice upon request.

Storage

Store at -20°C

Boiling Point

1566.5±65.0°C (Predicted)

In Vitro

The half-maximum inhibition concentrations (IC50) of α-amanitin, β-amanitin and γ-amanitin, and limits of detection (LODs, IC15) were 66.3, 97.4, 163.1 ng/mL and 0.91, 0.98, 0.89 ng/mL, respectively. The LODs for α-amanitin, β-amanitin and γ-amanitin in mushroom samples were 4.55, 4.9, and 4.45 ng/m.

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.

γ-Amanitin is a bicyclic octapeptide and a highly potent ADC cytotoxin employed as an ADC payload in antibody-drug conjugates. Its cytotoxic mechanism involves selective and irreversible inhibition of RNA polymerase II, resulting in suppression of mRNA transcription. This disruption of gene expression leads to arrest of protein synthesis and induces apoptosis in actively proliferating tumor cells. The unique structural features of γ-Amanitin, including the tryptathionine bridge and hydroxylated residues, enable stable conjugation to monoclonal antibodies via cleavable or non-cleavable linker chemistries. These linkers are designed to maintain systemic stability while facilitating controlled intracellular payload release within targeted tumor cells.

Within antibody-drug conjugates, γ-Amanitin is covalently attached to the antibody component using linkers that provide chemical stability in circulation and enable enzymatic or chemical cleavage inside tumor cells. The ADC remains inactive during systemic circulation, preventing premature cytotoxic effects. Following internalization through receptor-mediated endocytosis, intracellular processing releases the γ-Amanitin payload, which binds to RNA polymerase II and inhibits transcription. This site-specific mechanism ensures that the cytotoxic activity is confined to antigen-expressing cells, resulting in reproducible induction of apoptosis and consistent tumor-targeted activity. The ability to control linker cleavage and payload release is critical to optimizing pharmacokinetics and minimizing off-target toxicity in ADC design.

Applications of γ-Amanitin include its integration into ADCs targeting both solid tumors and hematologic malignancies with defined antigen expression. The payload is compatible with a range of linker chemistries, allowing modulation of conjugation efficiency, intracellular release kinetics, and pharmacokinetic behavior. In preclinical models, γ-Amanitin-based ADCs demonstrate consistent cytotoxicity in RNA polymerase II-expressing tumor cells. Its defined mechanism of action, precise intracellular activity, and compatibility with diverse ADC architectures make it suitable for incorporation into mechanistically controlled tumor-targeted therapeutic constructs, supporting highly specific antitumor strategies in ADC development.

Catalog	Product Name	CAS
BADC-00604	Mal-C6-α-Amanitin	1578249-76-9
BADC-00823	ε-Amanitin	21705-02-2
BADC-00724	ALPHA-AMANITIN	23109-05-9
BADC-01363	Dideoxy-amanitin	58255-46-2
BADC-00733	MC-vc-PAB-C6-a-amanitin

What is γ-Amanitin?

γ-Amanitin is a highly potent RNA polymerase II inhibitor derived from Amanita mushrooms, frequently utilized as an ADC payload. It selectively inhibits transcription in target cells, resulting in cell cycle arrest and apoptosis when delivered via antibody conjugates.

12/2/2022

Could you explain how γ-Amanitin enhances ADC specificity?

γ-Amanitin’s potency and mechanism allow ADCs to selectively target antigen-positive cells. The antibody facilitates precise delivery, minimizing systemic exposure and maximizing cytotoxic effect within the intended tumor population.

1/12/2018

We would like to know which linkers are compatible with γ-Amanitin.

γ-Amanitin can be conjugated via cleavable linkers responsive to intracellular conditions, such as disulfide or peptide-based linkers. These linkers ensure stable circulation and controlled release within the target cell for optimal ADC performance.

15/9/2018

Can γ-Amanitin be applied in preclinical ADC studies?

Yes, γ-Amanitin is commonly employed in preclinical ADC studies to assess cytotoxicity, pharmacokinetics, and efficacy. These studies are essential for ADC optimization and to predict clinical therapeutic potential.

2/9/2019

Good morning! What laboratory safety measures are required when handling γ-Amanitin?

Due to its extreme toxicity, γ-Amanitin handling requires strict safety protocols, including PPE, containment systems, and meticulous waste management to prevent exposure during research and conjugation procedures.

27/9/2018

— Dr. David Miller, Senior ADC Researcher (USA)

γ-Amanitin delivered by BOC Sciences had exceptional purity and stability.

15/9/2018

— Dr. William Scott, Toxicology Researcher (USA)

The γ-Amanitin supplied by BOC Sciences was of top quality, with purity levels suitable for ADC payload research.

27/9/2018

— Ms. Elisa Wagner, ADC Scientist (Germany)

We appreciated the complete analytical reports provided with γ-Amanitin, ensuring confidence in our experimental outcomes.

2/9/2019

— Dr. Robert Green, R&D Lead (UK)

γ-Amanitin was delivered on time, and its stability under storage conditions was better than expected.