Details of the Drug

General Information of Drug (ID: DM9FB2T)

• Drug Name: TPX-0005
• Synonyms: FIKPXCOQUIZNHB-RRKGBCIJSA-N; SCHEMBL20438940; TPX 0005; BCP19778

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[1]

• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 355.4
  Topological Polar Surface Area (xlogp); 2.1
  Rotatable Bond Count (rotbonds); 0
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 6
• Chemical Identifiers:
  Formula: C18H18FN5O2
  IUPAC Name: (3R,11S)-6-fluoro-3,11-dimethyl-10-oxa-2,13,17,18,21-pentazatetracyclo[13.5.2.04,9.018,22]docosa-1(21),4(9),5,7,15(22),16,19-heptaen-14-one
  Canonical SMILES: C[C@H]1CNC(=O)C2=C3N=C(C=CN3N=C2)N[C@@H](C4=C(O1)C=CC(=C4)F)C
  InChI: InChI=1S/C18H18FN5O2/c1-10-8-20-18(25)14-9-21-24-6-5-16(23-17(14)24)22-11(2)13-7-12(19)3-4-15(13)26-10/h3-7,9-11H,8H2,1-2H3,(H,20,25)(H,22,23)/t10-,11+/m0/s1
  InChIKey: FIKPXCOQUIZNHB-WDEREUQCSA-N
• Cross-matching ID:
  PubChem CID: 135565923
  CAS Number: 1802220-02-5
  TTD ID: D05NFR

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
ALK tyrosine kinase receptor (ALK)	TTPMQSO	ALK_HUMAN	Inhibitor	[1]
Proto-oncogene c-Ros (ROS1)	TTSZ6Y3	ROS1_HUMAN	Inhibitor	[1]
Tropomyosin-related kinase A (TrkA)	TTTDVOJ	NTRK1_HUMAN	Inhibitor	[1]

Molecular Expression Atlas of This Drug

• The Studied Disease: Solid tumour/cancer
• ICD Disease Classification: 2A00-2F9Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Tropomyosin-related kinase A (TrkA)	DTT	NTRK1	8.72E-01	-0.04	-0.22

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [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] Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 - Part I.Expert Opin Ther Pat. 2017 Jun;27(6):733-751.
• [8] National Cancer Institute Drug Dictionary (drug id 747694).
• [9] National Cancer Institute Drug Dictionary (drug id 766123).
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [11] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [12] 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. (Ligand id: 7397).
• [13] CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011 May 17;19(5):679-90.
• [14] PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models. Cancer Cell. 2015 Jul 13;28(1):70-81.
• [15] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [16] Treatment of ALK-positive non-small cell lung cancer. Arch Pathol Lab Med. 2012 Oct;136(10):1201-4.
• [17] Clinical pipeline report, company report or official report of AnHeart Therapeutics.
• [18] RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.