Marinobufagenin

Marinobufagenin (marinobufagin, MBG) is a cardiotonic bufadienolide steroid.^[1] It is secreted by the toad species such as Bufo marinus.^[1] It also can be found in the plasma and urine of human subjects with myocardial infarction, kidney failure, heart failure, and preeclampsia.^[2][3][4][5] MBG is a vasoconstrictor and a sodium–potassium adenosine triphosphatase (Na/K-ATPase) inhibitor with a high affinity for the alpha-1 isoform of the enzyme, the main isoform in the vascular wall and the kidney.^[6]

Quick facts Names, Identifiers ...

Marinobufagenin

Names
IUPAC name 3β,5-Dihydroxy-14,15-epoxy-5β,14β-bufa-20,22-dienolide
Systematic IUPAC name 5-[(1R,2aR,3aS,3bR,5aS,7S,9aR,9bS,11aR)-5b,7-Dihydroxy-9a,11a-dimethylhexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-1-yl]-2H-pyran-2-one
Other names Marinobufagin, Marinobufagenin
Identifiers
CAS Number	470-42-8 Y
3D model (JSmol)	Interactive image
ChemSpider	10142870 N
PubChem CID	11969465
UNII	3KBT25GV2B Y
CompTox Dashboard (EPA)	DTXSID5041063
InChI InChI=1S/C24H32O5/c1-21-8-5-15(25)12-23(21,27)10-7-17-16(21)6-9-22(2)18(11-19-24(17,22)29-19)14-3-4-20(26)28-13-14/h3-4,13,15-19,25,27H,5-12H2,1-2H3/t15-,16-,17+,18+,19+,21+,22+,23-,24+/m0/s1 N Key: JMNQTHQLNRILMH-OBBGIPBRSA-N N InChI=1/C24H32O5/c1-21-8-5-15(25)12-23(21,27)10-7-17-16(21)6-9-22(2)18(11-19-24(17,22)29-19)14-3-4-20(26)28-13-14/h3-4,13,15-19,25,27H,5-12H2,1-2H3/t15-,16-,17+,18+,19+,21+,22+,23-,24+/m0/s1 Key: JMNQTHQLNRILMH-OBBGIPBRBU
SMILES C[C@]12CC[C@@H](C[C@]1(CCC3C2CC[C@]4([C@]35[C@H](O5)C[C@@H]4C6=COC(=O)C=C6)C)O)O
Properties
Chemical formula	C24H32O5
Molar mass	400.515 g·mol−1
Hazards
Occupational safety and health (OHS/OSH):
Main hazards	Toxic
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

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It is produced by adrenal cortex and placenta via CYP27a1 pathway.^[7] MBG regulates the monovalent ions balance and cell homeostasis, and by binding to the Na/K-ATPase, it affects cell growth and differentiation, apoptosis, and proliferation.^[8] A novel effect of MBG is their ability to induce intracellular signaling, leading to a loss of elasticity and vascular fibrosis.^[9]

One of the mechanisms of the pro-fibrotic effect of MBG is the inhibition of the activity of Fli1, a nuclear transcription factor and a negative regulator of collagen 1 synthesis. Fli1 competes with another transcription factor, ETS-1, to maintain a balance between stimulation and repression of the collagen-1 gene. The Na/K ATPase/Src/EGFR complex emerges as a signal cascade, which activates phospholipase C, resulting in the phosphorylation of PKCδ and its translocation to the nucleus. In the nucleus, PKCδ phosphorylates Fli1, which withdraws the Fli1-induced inhibition of the collagen-1 promoter and increases procollagen expression and collagen production.^[10]

The antagonism of the pressor and profibrotic effects of MBG by monoclonal anti-MBG antibodies may lead to the prevention of vascular fibrosis in patients with end-stage renal disease and preeclampsia.^[11]