Details of the Drug

General Information of Drug (ID: DM1SWOY)

• Drug Name: MANUMYCIN A
• Synonyms: manumycin; Manumycin A; Ucfi-C; UNII-OIQ298X4XD; AC1O5PHE; OIQ298X4XD; CHEBI:29623; C31H38N2O7; 52665-74-4; 2,4-Decadienamide, N-(5-hydroxy-5-(7-((2-hydroxy-5-oxo-1-cyclopenten-1-yl)amino)-7-oxo-1,3,5-heptatrienyl)-2-oxo-7-oxabicyclo(4.1.0)hept-3-en-3-yl)-2,4,6-trimethyl-; (2E,4E,6R)-N-[(1S,5S,6R)-5-hydroxy-5-[(1E,3E,5E)-7-[(2-hydroxy-5-oxo-cyclopenten-1-yl)amino]-7-oxo-hepta-1,3,5-trienyl]-2-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl]-2,4,6-trimethyl-deca-2,4-dienamide; ( )-Manumycin A; BSPBio_001231; SCHEMBL12519093
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 550.6
  Logarithm of the Partition Coefficient (xlogp); 4.1
  Rotatable Bond Count (rotbonds); 12
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 7
• Chemical Identifiers:
  Formula: C31H38N2O7
  IUPAC Name: (2E,4E,6R)-N-[(1S,5S,6R)-5-hydroxy-5-[(1E,3E,5E)-7-[(2-hydroxy-5-oxocyclopenten-1-yl)amino]-7-oxohepta-1,3,5-trienyl]-2-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl]-2,4,6-trimethyldeca-2,4-dienamide
  Canonical SMILES: CCCC[C@@H](C)/C=C(\\C)/C=C(\\C)/C(=O)NC1=C[C@]([C@H]2[C@@H](C1=O)O2)(/C=C/C=C/C=C/C(=O)NC3=C(CCC3=O)O)O
  InChI: InChI=1S/C31H38N2O7/c1-5-6-11-19(2)16-20(3)17-21(4)30(38)32-22-18-31(39,29-28(40-29)27(22)37)15-10-8-7-9-12-25(36)33-26-23(34)13-14-24(26)35/h7-10,12,15-19,28-29,34,39H,5-6,11,13-14H2,1-4H3,(H,32,38)(H,33,36)/b8-7+,12-9+,15-10+,20-16+,21-17+/t19-,28-,29-,31+/m1/s1
  InChIKey: TWWQHCKLTXDWBD-MVTGTTCWSA-N
• Cross-matching ID:
  PubChem CID: 6438330
  ChEBI ID: CHEBI:29623
  CAS Number: 52665-74-4
  TTD ID: D0C2UY

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
CAAX farnesyltransferase beta (FNTB)	TT7WZIJ	FNTB_HUMAN	Inhibitor	[1]
Farnesyl protein transferase (Ftase)	TTXQKM3	FNTA_HUMAN ; FNTB_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[2]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Gene/Protein Processing	[2]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Gene/Protein Processing	[2]
GTPase HRas (HRAS)	OTWQN0DP	RASH_HUMAN	Gene/Protein Processing	[3]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Gene/Protein Processing	[2]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Post-Translational Modifications	[2]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Protein Interaction/Cellular Processes	[4]
Mitochondrial enolase superfamily member 1 (ENOSF1)	OT65D3ZK	ENOF1_HUMAN	Gene/Protein Processing	[5]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Protein Interaction/Cellular Processes	[6]
Signal transducer and activator of transcription 3 (STAT3)	OTAAGKYZ	STAT3_HUMAN	Post-Translational Modifications	[2]

Molecular Expression Atlas of This Drug

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Farnesyl protein transferase (Ftase)	DTT	FNTB; FNTA	5.43E-01	-0.1	-0.4

References

• [1] A novel metal-chelating inhibitor of protein farnesyltransferase. Bioorg Med Chem Lett. 2003 May 5;13(9):1523-6.
• [2] Manumycin inhibits STAT3, telomerase activity, and growth of glioma cells by elevating intracellular reactive oxygen species generation. Free Radic Biol Med. 2009 Aug 15;47(4):364-74.
• [3] Selective cytotoxicity of glycyrrhetinic acid against tumorigenic r/m HM-SFME-1 cells: potential involvement of H-Ras downregulation. Toxicol Lett. 2010 Feb 15;192(3):425-30. doi: 10.1016/j.toxlet.2009.11.021. Epub 2009 Dec 1.
• [4] Involvement of H-Ras and reactive oxygen species in proinflammatory cytokine-induced matrix metalloproteinase-13 expression in human articular chondrocytes. Arch Biochem Biophys. 2011 Mar 15;507(2):350-5. doi: 10.1016/j.abb.2010.12.032. Epub 2011 Jan 3.
• [5] Expression of rTSbeta as a 5-fluorouracil resistance marker in patients with primary breast cancer. Oncol Rep. 2008 Apr;19(4):881-8.
• [6] Proteomic identification of heat shock protein 70 as a candidate target for enhancing apoptosis induced by farnesyl transferase inhibitor. Proteomics. 2003 Oct;3(10):1904-11. doi: 10.1002/pmic.200300547.