Record Information
Version2.0 (beta)
Creation Date2010-05-26 10:48:09 -0600
Update Date2014-09-22 00:07:01 -0600
Accession NumberT3D3774
Identification
Common NameSecalonic Acid D
ClassSmall Molecule
DescriptionSecalonic acid D (SAD) is a mycotoxin produced by the fungus Pencillium oxalicum, which is a common contaminant in corn and other grains. Secalonic acid D is a human teratogen that induces cleft palate. (1)
Compound Type
  • Organic Compound
  • Mycotoxin
Chemical Structure
Thumb
Synonyms
  1. Secalonic acid D
  2. Secalonsaure D
  3. Secalonic acid D mycotoxin
  4. Ergochrome AA (2,2')-5-beta,6-alpha,10-beta-5',6'-alpha,10'-beta
  5. (7,7'-Bi-4aH-xanthene)-4a,4'a-dicarboxylic acid, 2,2',3,3',4,4',9,9'-octahydro-1,1',4,4',8,8'-hexahydroxy-3,3'-dimethyl-9,9'-dioxo-, dimethyl ester, (3S-(3-alpha,4-beta,4a-beta,7(3'R,4'S,4'aS)))
  6. SAD
  7. SID561521
Chemical FormulaC32H30O14
Average Molecular Mass638.5722 g/mol
Monoisotopic Mass638.163555668 g/mol
CAS Registry Number35287-69-5
IUPAC Namemethyl 4,8,9-trihydroxy-3-methyl-1-oxo-7-[4,8,9-trihydroxy-4a-(methoxycarbonyl)-3-methyl-1-oxo-2,3,4,4a-tetrahydro-1H-xanthen-7-yl]-2,3,4,4a-tetrahydro-1H-xanthene-4a-carboxylate
Traditional IUPAC Namesecalonic acid D
SMILESCOC(=O)C12OC3=C(C(O)=C(C=C3)C3=C(O)C4=C(OC5(C(O)C(C)CC(=O)C5=C4O)C(=O)OC)C=C3)C(O)=C1C(=O)CC(C)C2O
InChI IdentifierInChI=1S/C32H30O14/c1-11-9-15(33)21-25(37)19-17(45-31(21,27(11)39)29(41)43-3)7-5-13(23(19)35)14-6-8-18-20(24(14)36)26(38)22-16(34)10-12(2)28(40)32(22,46-18)30(42)44-4/h5-8,11-12,27-28,35-40H,9-10H2,1-4H3
InChI KeyInChIKey=NFZJAYYORNVZNI-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassHeterocyclic Compounds
ClassBenzopyrans
Sub Class1-Benzopyrans
Direct ParentXanthenes
Alternative Parents
  • Biphenyls and Derivatives
  • Beta-Hydroxy Acids and Derivatives
  • Alkyl Aryl Ethers
  • Cyclohexanones
  • Dicarboxylic Acids and Derivatives
  • Vinylogous Esters
  • Methyl Esters
  • Vinylogous Acids
  • Polyols
  • Cyclic Alcohols and Derivatives
  • Secondary Alcohols
  • Carboximidic Acids and Derivatives
  • Enols
  • Aromatic Alcohols
Substituents
  • carboxylic acid ester
  • alkyl aryl ether
  • cyclic alcohol
  • secondary alcohol
  • polyol
  • alcohol
  • hydroxy acid
  • enol
  • carboximidic acid derivative
  • xanthene
  • beta-hydroxy acid
  • Benzenoid
  • Ether
  • Aromatic Alcohol
  • Organooxygen Compound
  • Aromatic Heteropolycyclic Compound
  • Vinylogous Ester
  • Vinylogous Acid
  • Carbonyl Group
  • Carboxylic Acid Derivative
  • Dicarboxylic Acid or Derivative
  • Methyl Ester
  • Biphenyl
  • Cyclohexanone
External DescriptorsNot Available
Biological Properties
StatusDetected but not Quantified
OriginNot Available
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateNot Available
AppearanceNot Available
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
water solubility2.81e-01 g/lALOGPS
logP1.62ALOGPS
logP1.19ChemAxon
logS-3.4ALOGPS
pKa (strongest acidic)5.57ChemAxon
pKa (strongest basic)-3.5ChemAxon
physiological charge-2ChemAxon
hydrogen acceptor count12ChemAxon
hydrogen donor count6ChemAxon
polar surface area226.58ChemAxon
rotatable bond count5ChemAxon
refractivity156.5ChemAxon
polarizability63.29ChemAxon
Spectra
SpectraNot Available
Toxicity Profile
Route of ExposureOral, dermal, inhalation, and parenteral (contaminated drugs). (4)
Mechanism of ToxicitySecalonic acid D (SAD) is though to induce cleft palate by causing the formation of smaller palatal shelves that fail to elevate and fuse. This inhibited palatal shelf growth is a result of the of SAD causing reduced proliferation of embryonic palatal mesenchymal (HEPM) cells. SAD binds to and phosphorylates cAMP response element binding protein (CREB), an important transcription factor required for the expression of numerous genes including proliferating cell nuclear antigen (PCNA) gene. The phosphorylation of CREB by SAD prevents it from forming the necessary transcription factor-cAMP response element complex at transcription start sites, so these genes are not expressed. This leads to reduced palatal mesenchymal cell number causing reduced palatal shelf growth and thus cleft palate. (1, 2, 3)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not Available
Uses/SourcesSecalonic acid D (SAD) is a mycotoxin produced by the fungus Pencillium oxalicum, which is a common contaminant in corn and other grains. (1)
Minimum Risk LevelNot Available
Health EffectsSecalonic acid D is a human teratogen that induces cleft palate. (1)
SymptomsCleft palate is a congenital deformity characterized by a gap on the roof of the mouth that is present at birth. (3)
TreatmentCleft palate can be treated with corrective surgery. (3)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID73431
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDNot Available
OMIM IDNot Available
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Dhulipala VC, Maddali KK, Welshons WV, Reddy CS: Secalonic acid D blocks embryonic palatal mesenchymal cell-cycle by altering the activity of CDK2 and the expression of p21 and cyclin E. Birth Defects Res B Dev Reprod Toxicol. 2005 Jun;74(3):233-42. [15880679 ]
  2. Hanumegowda UM, Dhulipala VC, Reddy CS: Mechanism of secalonic acid D-induced inhibition of transcription factor binding to cyclic AMP response element in the developing murine palate. Toxicol Sci. 2002 Nov;70(1):55-62. [12388835 ]
  3. Hanumegowda UM, Judy BM, Welshons WV, Reddy CS: Selective inhibition of murine palatal mesenchymal cell proliferation in vitro by secalonic acid D. Toxicol Sci. 2002 Mar;66(1):159-65. [11861983 ]
  4. Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General function:
Involved in transcription factor activity
Specific function:
This protein binds the cAMP response element (CRE), a sequence present in many viral and cellular promoters. CREB stimulates transcription on binding to the CRE
Gene Name:
CREB1
Uniprot ID:
P16220
Molecular weight:
36688.0
References
  1. Dhulipala VC, Maddali KK, Welshons WV, Reddy CS: Secalonic acid D blocks embryonic palatal mesenchymal cell-cycle by altering the activity of CDK2 and the expression of p21 and cyclin E. Birth Defects Res B Dev Reprod Toxicol. 2005 Jun;74(3):233-42. [15880679 ]
  2. Hanumegowda UM, Dhulipala VC, Reddy CS: Mechanism of secalonic acid D-induced inhibition of transcription factor binding to cyclic AMP response element in the developing murine palate. Toxicol Sci. 2002 Nov;70(1):55-62. [12388835 ]
  3. Hanumegowda UM, Judy BM, Welshons WV, Reddy CS: Selective inhibition of murine palatal mesenchymal cell proliferation in vitro by secalonic acid D. Toxicol Sci. 2002 Mar;66(1):159-65. [11861983 ]
General function:
Involved in viral process
Specific function:
Endoplasmic reticulum (ER)-bound transcription factor that plays a role in the unfolded protein response (UPR). Involved in cell proliferation and migration, tumor suppression and inflammatory gene expression. Plays also a role in the human immunodeficiency virus type 1 (HIV-1) virus protein expression and in the herpes simplex virus-1 (HSV-1) latent infection and reactivation from latency. Isoform 2 plays a role in the unfolded protein response (UPR). Isoform 2 acts as a positive regulator of LKN-1/CCL15-induced chemotaxis signaling of leukocyte cell migration. Isoform 2 may play a role as a cellular tumor suppressor that is targeted by the hepatitis C virus (HSV) core protein. Isoform 2 represses the VP16-mediated transactivation of immediate early genes of the HSV-1 virus by sequestring host cell factor-1 HCFC1 in the ER membrane of sensory neurons, thereby preventing the initiation of the replicative cascade leading to latent infection. Isoform 3 functions as a negative transcriptional regulator in ligand-induced transcriptional activation of the glucocorticoid receptor NR3C1 by recruiting and activating histone deacetylases (HDAC1, HDAC2 and HDAC6). Isoform 3 decreases the acetylation level of histone H4. Isoform 3 does not promote the chemotactic activity of leukocyte cells.Processed cyclic AMP-responsive element-binding protein 3: acts as a transcription factor that activates unfolded protein response (UPR) target genes during endoplasmic reticulum (ER) stress response. Promotes cell survival against ER stress-induced apoptotic cell death during UPR. Activates transcription from CRE and C/EBP-containing reporter genes. Induces transcriptional activation of chemokine receptors. Activates transcription of genes required for reactivation of the latent HSV-1 virus. Down-regulates Tat-dependent transcription of the HIV-1 LTR by interacting with HIV-1 Tat. It's transcriptional activity is inhibited by CREBZF in a HCFC1-dependent manner, by the viral transactivator protein VP16 and by the HCV core protein. Binds DNA to the cAMP response element (CRE) (consensus: 5'-GTGACGT[AG][AG]-3') and C/EBP sequences present in many viral and cellular promoters. Binds to the unfolded protein respons element (UPRE) consensus sequences sites. Binds DNA to the 5'-CCAC[GA]-3'half of ERSE II (5'-ATTGG-N-CCACG-3'). Associates with chromatin to the HERPUD1 promoter.
Gene Name:
CREB3
Uniprot ID:
O43889
Molecular weight:
43916.65
References
  1. Dhulipala VC, Maddali KK, Welshons WV, Reddy CS: Secalonic acid D blocks embryonic palatal mesenchymal cell-cycle by altering the activity of CDK2 and the expression of p21 and cyclin E. Birth Defects Res B Dev Reprod Toxicol. 2005 Jun;74(3):233-42. [15880679 ]
  2. Hanumegowda UM, Dhulipala VC, Reddy CS: Mechanism of secalonic acid D-induced inhibition of transcription factor binding to cyclic AMP response element in the developing murine palate. Toxicol Sci. 2002 Nov;70(1):55-62. [12388835 ]
  3. Hanumegowda UM, Judy BM, Welshons WV, Reddy CS: Selective inhibition of murine palatal mesenchymal cell proliferation in vitro by secalonic acid D. Toxicol Sci. 2002 Mar;66(1):159-65. [11861983 ]
General function:
Involved in transcription from RNA polymerase II promoter
Specific function:
Binds to the cAMP response element and activates transcription.
Gene Name:
CREB5
Uniprot ID:
Q02930
Molecular weight:
56918.115
References
  1. Dhulipala VC, Maddali KK, Welshons WV, Reddy CS: Secalonic acid D blocks embryonic palatal mesenchymal cell-cycle by altering the activity of CDK2 and the expression of p21 and cyclin E. Birth Defects Res B Dev Reprod Toxicol. 2005 Jun;74(3):233-42. [15880679 ]
  2. Hanumegowda UM, Dhulipala VC, Reddy CS: Mechanism of secalonic acid D-induced inhibition of transcription factor binding to cyclic AMP response element in the developing murine palate. Toxicol Sci. 2002 Nov;70(1):55-62. [12388835 ]
  3. Hanumegowda UM, Judy BM, Welshons WV, Reddy CS: Selective inhibition of murine palatal mesenchymal cell proliferation in vitro by secalonic acid D. Toxicol Sci. 2002 Mar;66(1):159-65. [11861983 ]
4. activator protein 1
References
  1. Dhulipala VC, Maddali KK, Welshons WV, Reddy CS: Secalonic acid D blocks embryonic palatal mesenchymal cell-cycle by altering the activity of CDK2 and the expression of p21 and cyclin E. Birth Defects Res B Dev Reprod Toxicol. 2005 Jun;74(3):233-42. [15880679 ]
  2. Hanumegowda UM, Dhulipala VC, Reddy CS: Mechanism of secalonic acid D-induced inhibition of transcription factor binding to cyclic AMP response element in the developing murine palate. Toxicol Sci. 2002 Nov;70(1):55-62. [12388835 ]
  3. Hanumegowda UM, Judy BM, Welshons WV, Reddy CS: Selective inhibition of murine palatal mesenchymal cell proliferation in vitro by secalonic acid D. Toxicol Sci. 2002 Mar;66(1):159-65. [11861983 ]