Details of the Drug

General Information of Drug (ID: DMGTAWC)

• Drug Name: RKI-1447
• Synonyms: RKI1447; compound 5g [PMID 23275831]

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); 326.4
  Topological Polar Surface Area (xlogp); 2
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C16H14N4O2S
  IUPAC Name: 1-[(3-hydroxyphenyl)methyl]-3-(4-pyridin-4-yl-1,3-thiazol-2-yl)urea
  Canonical SMILES: C1=CC(=CC(=C1)O)CNC(=O)NC2=NC(=CS2)C3=CC=NC=C3
  InChI: InChI=1S/C16H14N4O2S/c21-13-3-1-2-11(8-13)9-18-15(22)20-16-19-14(10-23-16)12-4-6-17-7-5-12/h1-8,10,21H,9H2,(H2,18,19,20,22)
  InChIKey: GDVRVPIXWXOKQO-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 60138149
  TTD ID: D03CPB

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
CDC42 binding protein kinase alpha (DMPK-like alpha)	TT5Z0EF	MRCKA_HUMAN	Inhibitor	[1]
DMPK messenger RNA (DMPK mRNA)	TTZQTY2	DMPK_HUMAN	Inhibitor	[1]
LIM domain kinase-1 (LIMK-1)	TTWL9TY	LIMK1_HUMAN	Inhibitor	[1]
Myosin light kinase (MYLK)	TT18ETS	MYLK_HUMAN	Inhibitor	[1]
PAK-1 protein kinase (PAK1)	TTFN95D	PAK1_HUMAN	Inhibitor	[1]
Protein kinase N1 (PKN1)	TTSL41O	PKN1_HUMAN	Inhibitor	[1]
Rho-associated protein kinase 1 (ROCK1)	TTZN7RP	ROCK1_HUMAN	Inhibitor	[1]
Rho-associated protein kinase 2 (ROCK2)	TTGWKQJ	ROCK2_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
Rho-associated protein kinase 2 (ROCK2)	DTT	ROCK2	1.55E-01	0.12	0.71

References

• [1] Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2). Medchemcomm. 2012 Jun 1;3(6):699-709.
• [2] Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism. Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16814-9.
• [3] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [4] Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. 2007 Jan;320(1):89-98.
• [5] Rho kinase inhibitors: a patent review (2014 - 2016).Expert Opin Ther Pat. 2017 Apr;27(4):507-515.
• [6] 2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles. Bioorg Med Chem Lett. 2010 Jan 15;20(2):679-83.
• [7] PAK1: A Therapeutic Target for Cancer Treatment. ACS Med Chem Lett. 2013 Mar 19;4(5):431-2.
• [8] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [9] The Rho kinase inhibitor SAR407899 potently inhibits endothelin-1-induced constriction of renal resistance arteries. J Hypertens. 2012 May;30(5):980-9.
• [10] Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19.
• [11] 7,8-dichloro-1-oxo-beta-carbolines as a versatile scaffold for the development of potent and selective kinase inhibitors with unusual binding modes. J Med Chem. 2012 Jan 12;55(1):403-13.
• [12] Clinical pipeline report, company report or official report of ISIS Pharmaceuticals.
• [13] 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: 1505).
• [14] Modulation of cofilin phosphorylation by inhibition of the Lim family kinases. Bioorg Med Chem Lett. 2012 Sep 15;22(18):5995-8.
• [15] Novel class of LIM-kinase 2 inhibitors for the treatment of ocular hypertension and associated glaucoma. J Med Chem. 2009 Nov 12;52(21):6515-8.
• [16] ME-3407, a new antiulcer agent, inhibits acid secretion by interfering with redistribution of H(+)-K(+)-ATPase. Am J Physiol. 1997 May;272(5 Pt 1):G1122-34.