Details of the Drug

General Information of Drug (ID: DMB38KH)

• Drug Name: Elisidepsin
• Synonyms: Irvalec; Elisidepsin trifluoroacetate; PM-02734; Erbb3 tyrosine kinase receptor inhibitor (cancer), PharmaMar; Kahalalide therapy (solid tumor), PharmaMar

Indication

Disease Entry	ICD 11	Status	REF
Psoriasis vulgaris	EA90	Phase 2	[1]

• #Ro5 Violations (Lipinski): 5:
  Molecular Weight (mw); 1477.9
  Topological Polar Surface Area (xlogp); 7.4
  Rotatable Bond Count (rotbonds); 33
  Hydrogen Bond Donor Count (hbonddonor); 14
  Hydrogen Bond Acceptor Count (hbondacc); 17
• Chemical Identifiers:
  Formula: C75H124N14O16
  IUPAC Name: (2R)-N-[(2S)-5-amino-1-[[(2R,3S)-1-[[(3S,6Z,9S,12R,15R,18R,19R)-9-benzyl-15-[(2S)-butan-2-yl]-6-ethylidene-19-methyl-2,5,8,11,14,17-hexaoxo-3,12-di(propan-2-yl)-1-oxa-4,7,10,13,16-pentazacyclononadec-18-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]-1-[(2R)-2-[[(2S)-2-[[(2S,3R)-3-hydroxy-2-[[(2R)-3-methyl-2-[[(4S)-4-methylhexanoyl]amino]butanoyl]amino]butanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carboxamide
  Canonical SMILES: CC[C@H](C)CCC(=O)N[C@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@@H](CCCN)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]2[C@H](OC(=O)[C@@H](NC(=O)/C(=C/C)/NC(=O)[C@@H](NC(=O)[C@H](NC(=O)[C@H](NC2=O)[C@@H](C)CC)C(C)C)CC3=CC=CC=C3)C(C)C)C
  InChI: InChI=1S/C75H124N14O16/c1-20-43(15)33-34-53(91)80-54(38(5)6)68(97)87-61(46(18)90)72(101)82-56(40(9)10)69(98)83-57(41(11)12)74(103)89-36-28-32-52(89)66(95)78-50(31-27-35-76)64(93)85-59(44(16)21-2)71(100)88-62-47(19)105-75(104)58(42(13)14)84-63(92)49(23-4)77-65(94)51(37-48-29-25-24-26-30-48)79-67(96)55(39(7)8)81-70(99)60(45(17)22-3)86-73(62)102/h23-26,29-30,38-47,50-52,54-62,90H,20-22,27-28,31-37,76H2,1-19H3,(H,77,94)(H,78,95)(H,79,96)(H,80,91)(H,81,99)(H,82,101)(H,83,98)(H,84,92)(H,85,93)(H,86,102)(H,87,97)(H,88,100)/b49-23-/t43-,44-,45-,46+,47+,50-,51-,52+,54+,55+,56-,57+,58-,59+,60+,61-,62+/m0/s1
  InChIKey: ZNVCPJPCKSJWDH-UCTDCHLSSA-N
• Cross-matching ID:
  PubChem CID: 9855343
  ChEBI ID: CHEBI:83152
  TTD ID: D08GIM

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Erbb3 tyrosine kinase receptor (Erbb-3)	TTDC8N2	ERBB3_HUMAN	Inhibitor	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Psoriasis vulgaris
• ICD Disease Classification: EA90

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Erbb3 tyrosine kinase receptor (Erbb-3)	DTT	ERBB3	7.21E-05	-0.32	-0.62

References

• [1] First-in-human, phase I study of elisidepsin (PM02734) administered as a 30-min or as a 3-hour intravenous infusion every three weeks in patients with advanced solid tumors. Invest New Drugs. 2015 Aug;33(4):901-10.
• [2] Molecular pharmacodynamics of PM02734 (elisidepsin) as single agent and in combination with erlotinib; synergistic activity in human non-small cell lung cancer cell lines and xenograft models. Eur J Cancer. 2009 Jul;45(10):1855-64.
• [3] MM-141, an IGF-IR- and ErbB3-directed bispecific antibody, overcomes network adaptations that limit activity of IGF-IR inhibitors. Mol Cancer Ther. 2014 Feb;13(2):410-25.
• [4] Company report (Biooncology)
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Company report (Merrimack)
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Clinical pipeline report, company report or official report of Merus.
• [9] An antibody that locks HER3 in the inactive conformation inhibits tumor growth driven by HER2 or neuregulin. Cancer Res. 2013 Oct 1;73(19):6024-35.
• [10] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1798).