Details of the Drug

General Information of Drug (ID: DM8MXS6)

• Drug Name: ZD-6021
• Synonyms: 255049-08-2

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 632.6
  Topological Polar Surface Area (xlogp); 7.1
  Rotatable Bond Count (rotbonds); 9
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C35H35Cl2N3O2S
  IUPAC Name: 3-cyano-N-[(2S)-2-(3,4-dichlorophenyl)-4-[4-[2-[(S)-methylsulfinyl]phenyl]piperidin-1-yl]butyl]-N-methylnaphthalene-1-carboxamide
  Canonical SMILES: CN(C[C@@H](CCN1CCC(CC1)C2=CC=CC=C2[S@@](=O)C)C3=CC(=C(C=C3)Cl)Cl)C(=O)C4=CC(=CC5=CC=CC=C54)C#N
  InChI: InChI=1S/C35H35Cl2N3O2S/c1-39(35(41)31-20-24(22-38)19-27-7-3-4-8-29(27)31)23-28(26-11-12-32(36)33(37)21-26)15-18-40-16-13-25(14-17-40)30-9-5-6-10-34(30)43(2)42/h3-12,19-21,25,28H,13-18,23H2,1-2H3/t28-,43+/m1/s1
  InChIKey: SJHZTGDJTIZMSK-KPRDSAADSA-N
• Cross-matching ID:
  PubChem CID: 9852253
  TTD ID: D0Z6TG

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Substance-K receptor (TACR2)	TTYO0A3	NK2R_HUMAN	Modulator	[1], [1], [2]
Substance-P receptor (TACR1)	TTZPO1L	NK1R_HUMAN	Modulator	[1], [1], [2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Discovery agent
• ICD Disease Classification: N.A.

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Substance-P receptor (TACR1)	DTT	TACR1	7.40E-01	0.02	0.07
Substance-P receptor (TACR1)	DTT	TACR1	8.57E-01	-0.02	-0.18

References

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• [2] Molecular cloning, mutations and effects of NK1 receptor antagonists reveal the human-like pharmacology of gerbil NK1 receptors.Biochem Pharmacol.2007 Jan 15;73(2):259-69.
• [3] Potent, brain-penetrant, hydroisoindoline-based human neurokinin-1 receptor antagonists. J Med Chem. 2009 May 14;52(9):3039-46.
• [4] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [5] Netupitant and palonosetron trigger NK1 receptor internalization in NG108-15 cells. Exp Brain Res. 2014 Aug;232(8):2637-44.
• [6] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Stress-related neuropeptides and alcoholism: CRH, NPY and beyond. Alcohol. 2009 November; 43(7): 491-498.
• [9] A review of drug options in age-related macular degeneration therapy and potential new agents. Expert Opin Pharmacother. 2006 Dec;7(17):2355-68.
• [10] Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenicchemotherapy: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jun;10(6):549-58.
• [11] Antagonist profile of ibodutant at the tachykinin NK2 receptor in guinea pig isolated bronchi. Eur J Pharmacol. 2013 Nov 15;720(1-3):180-5.
• [12] Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5088-92.
• [13] Pharmacology of an original and selective nonpeptide antagonist ligand for the human tachykinin NK2 receptor. Eur J Pharmacol. 2005 Jun 1;516(2):104-11.
• [14] Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26.
• [15] Characterization of species-related differences in the pharmacology of tachykinin NK receptors 1, 2 and 3. Biochem Pharmacol. 2009 May 1;77(9):1522-30.
• [16] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [17] Effects of FK224, a novel compound NK1 and NK2 receptor antagonist, on airway constriction and airway edema induced by neurokinins and sensory nerv... J Pharmacol Exp Ther. 1992 Jul;262(1):403-8.
• [18] Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients. Eur Respir J. 2004 Jan;23(1):76-81.
• [19] Effect of an NK1/NK2 receptor antagonist on airway responses and inflammation to allergen in asthma. Am J Respir Crit Care Med. 2007 Mar 1;175(5):450-7.
• [20] Pharmacokinetics and metabolism of a sulphamide NK2 antagonist in rat, dog and human. Xenobiotica. 2000 Jun;30(6):627-42.