Details of the Drug

General Information of Drug (ID: DMCZPH4)

• Drug Name: K-252a analogue

Indication

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

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 455.5
  Topological Polar Surface Area (xlogp); 2.8
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 4
• Chemical Identifiers:
  Formula: C27H25N3O4
  IUPAC Name: 3-[(2R,4R)-4-hydroxy-4-(hydroxymethyl)-5,5-dimethyloxolan-2-yl]-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4,6,8,10,15,17,19,21-nonaen-12-one
  Canonical SMILES: CC1([C@@](C[C@@H](O1)N2C3=CC=CC=C3C4=C5C(=C6C7=CC=CC=C7NC6=C42)CNC5=O)(CO)O)C
  InChI: InChI=1S/C27H25N3O4/c1-26(2)27(33,13-31)11-19(34-26)30-18-10-6-4-8-15(18)21-22-16(12-28-25(22)32)20-14-7-3-5-9-17(14)29-23(20)24(21)30/h3-10,19,29,31,33H,11-13H2,1-2H3,(H,28,32)/t19-,27-/m1/s1
  InChIKey: ONSKSKMJNHEONW-XHCCPWGMSA-N
• Cross-matching ID:
  PubChem CID: 44400432
  TTD ID: D02RWK

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Tropomyosin-related kinase A (TrkA)	TTTDVOJ	NTRK1_HUMAN	Inhibitor	[1]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[1]

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
Vascular endothelial growth factor receptor 2 (KDR)	DTT	KDR	1.98E-01	0.11	0.2
Tropomyosin-related kinase A (TrkA)	DTT	NTRK1	8.72E-01	-0.04	-0.22

References

• [1] Synthesis, modeling, and in vitro activity of (3'S)-epi-K-252a analogues. Elucidating the stereochemical requirements of the 3'-sugar alcohol on tr... J Med Chem. 2005 Jun 2;48(11):3776-83.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [3] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [4] Safety and efficacy of MIM-D3 ophthalmic solutions in a randomized, placebo-controlled Phase 2 clinical trial in patients with dry eye. Clin Ophthalmol. 2013; 7: 1275-1285.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Topical TrkA Kinase Inhibitor CT327 is an Effective, Novel Therapy for the Treatment of Pruritus due to Psoriasis: Results from Experimental Studies, and Efficacy and Safety of CT327 in a Phase 2b Clinical Trial in Patients with Psoriasis. Acta Derm Venereol. 2015 May;95(5):542-8.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 - Part I.Expert Opin Ther Pat. 2017 Jun;27(6):733-751.
• [9] National Cancer Institute Drug Dictionary (drug id 747694).
• [10] National Cancer Institute Drug Dictionary (drug id 766123).
• [11] Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
• [12] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [13] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [14] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [15] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [16] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [17] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [18] Clinical pipeline report, company report or official report of Exelixis (2011).
• [19] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [20] Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.