Details of the Drug

General Information of Drug (ID: DMD51RN)

• Drug Name: TAK-448

Indication

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Phase 2	[1]

• #Ro5 Violations (Lipinski): 4:
  Molecular Weight (mw); 1225.4
  Logarithm of the Partition Coefficient (xlogp); -1.2
  Rotatable Bond Count (rotbonds); 31
  Hydrogen Bond Donor Count (hbonddonor); 17
  Hydrogen Bond Acceptor Count (hbondacc); 15
• Chemical Identifiers:
  Formula: C58H80N16O14
  IUPAC Name: (2S)-2-[[(2S,4R)-1-[(2R)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]-4-hydroxypyrrolidine-2-carbonyl]amino]-N-[(2S,3R)-1-[[(2S)-1-[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-[(N'-methylcarbamimidoyl)amino]-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]hydrazinyl]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]butanediamide
  Canonical SMILES: C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NNC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=NC)N)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N)NC(=O)[C@H](CC(=O)N)NC(=O)[C@@H]4C[C@H](CN4C(=O)[C@@H](CC5=CC=C(C=C5)O)NC(=O)C)O)O
  InChI: InChI=1S/C58H80N16O14/c1-30(2)22-42(51(82)66-40(16-11-21-63-57(61)62-5)50(81)67-41(49(60)80)25-35-28-64-39-15-10-9-14-38(35)39)70-58(88)73-72-53(84)43(23-33-12-7-6-8-13-33)69-55(86)48(31(3)75)71-52(83)44(27-47(59)79)68-54(85)46-26-37(78)29-74(46)56(87)45(65-32(4)76)24-34-17-19-36(77)20-18-34/h6-10,12-15,17-20,28,30-31,37,40-46,48,64,75,77-78H,11,16,21-27,29H2,1-5H3,(H2,59,79)(H2,60,80)(H,65,76)(H,66,82)(H,67,81)(H,68,85)(H,69,86)(H,71,83)(H,72,84)(H3,61,62,63)(H2,70,73,88)/t31-,37-,40+,41+,42+,43+,44+,45-,46+,48+/m1/s1
  InChIKey: MWXWMWSUUYXMRA-GRKBUMBKSA-N
• Cross-matching ID:
  PubChem CID: 46700761
  CAS Number: 1234319-68-6
  DrugBank ID: DB11975
  TTD ID: D04GEI

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Metastasis-suppressor KiSS-1 (KISS1)	TTU2O6T	KISS1_HUMAN	Modulator	[2]

Molecular Expression Atlas of This Drug

• ICD Disease Classification: 02 Neoplasm
• Disease Class: ICD-11: 2C82 Prostate cancer
• The Studied Tissue: Prostate
• The Studied Disease: Prostate cancer [ICD-11:2C82]

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Metastasis-suppressor KiSS-1 (KISS1)	DTT	KISS1	6.40E-01	-0.01	-0.04

References

• [1] ClinicalTrials.gov (NCT02381288) Effects of TAK-448 in Middle-aged and Older Men With Low Testosterone. U.S. National Institutes of Health.
• [2] Pharmacologic profiles of investigational kisspeptin/metastin analogues, TAK-448 and TAK-683, in adult male rats in comparison to the GnRH analogue leuprolide.Eur J Pharmacol.2014 Jul 15;735:77-85.