Details of the Drug

General Information of Drug (ID: DMI8217)

• Drug Name: PMID22136433C20
• Synonyms: NSC748497; NSC-748497; KH-CARB13; GTPL8156; BDBM50363167

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); 363.2
  Topological Polar Surface Area (xlogp); 2.3
  Rotatable Bond Count (rotbonds); 0
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 3
• Chemical Identifiers:
  Formula: C17H16Cl2N4O
  IUPAC Name: 7,8-dichloro-9-methyl-1-oxospiro[2,4-dihydropyrido[3,4-b]indole-3,4'-piperidine]-4-carbonitrile
  Canonical SMILES: CN1C2=C(C=CC(=C2Cl)Cl)C3=C1C(=O)NC4(C3C#N)CCNCC4
  InChI: InChI=1S/C17H16Cl2N4O/c1-23-14-9(2-3-11(18)13(14)19)12-10(8-20)17(4-6-21-7-5-17)22-16(24)15(12)23/h2-3,10,21H,4-7H2,1H3,(H,22,24)
  InChIKey: OWAWOKKHZNRHGV-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 54613583
  TTD ID: D06HVH

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Calmodulin-dependent kinase II (CAMKK2)	TTV298Y	KKCC2_HUMAN	Inhibitor	[1]
PIM-3 protein kinase (PIM3)	TTCGOIN	PIM3_HUMAN	Inhibitor	[1]
Protein kinase N1 (PKN1)	TTSL41O	PKN1_HUMAN	Inhibitor	[1]
Serine/threonine-protein kinase pim-1 (PIM1)	TTTN5QW	PIM1_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
Serine/threonine-protein kinase pim-1 (PIM1)	DTT	PIM1	4.83E-01	0.06	0.2
PIM-3 protein kinase (PIM3)	DTT	PIM3	7.86E-06	0.78	3.44

References

• [1] 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.
• [2] Tricyclic compounds for use as kinase inhibitors. US9682991.
• [3] Substituted pyrido[2,3-d]pyrimidin-7(8H)-ones and therapeutic uses thereof. US8889696.
• [4] PIM kinase inhibitors and methods of their use. US8829193.
• [5] Azole compounds as PIM inhibitors. US9321756.
• [6] Bicyclic aromatic carboxamide compounds useful as Pim kinase inhibitors. US9580418.
• [7] Pyrrolo[2,3-a] carbazoles and use thereof as PIM kinase inhibitors. US8481586.
• [8] 5-azaindazole compounds and methods of use. US9434725.
• [9] Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use. US9573943.
• [10] 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: 2158).
• [11] 123 Antitumor activity of CXR1002, a novel anti-cancer clinical phase compound that induces ER stress and inhibits PIM kinases: Human tumor xenograft efficacy and in vitro mode of action. EJC Supplements, 2010; 8(7):45-46.
• [12] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [13] Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing. J Med Chem. 2011 Jun 23;54(12):4172-86.
• [14] 7-(4H-1,2,4-Triazol-3-yl)benzo[c][2,6]naphthyridines: a novel class of Pim kinase inhibitors with potent cell antiproliferative activity. Bioorg Med Chem Lett. 2011 Nov 15;21(22):6687-92.
• [15] Pim-1 inhibitor SMI-4a suppresses tumor growth in non-small cell lung cancer via PI3K/AKT/mTOR pathway. Onco Targets Ther. 2019 Apr 23;12:3043-3050.
• [16] Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2). Medchemcomm. 2012 Jun 1;3(6):699-709.
• [17] Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof. US9623028.
• [18] STO-609, a specific inhibitor of the Ca(2+)/calmodulin-dependent protein kinase kinase. J Biol Chem. 2002 May 3;277(18):15813-8.