Details of the Drug

General Information of Drug (ID: DMCJXWK)

• Drug Name: URMC-099
• Synonyms: compound 1 [PMID 24044867]

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); 421.5
  Topological Polar Surface Area (xlogp); 4.3
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 3
• Chemical Identifiers:
  Formula: C27H27N5
  IUPAC Name: 3-(1H-indol-5-yl)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridine
  Canonical SMILES: CN1CCN(CC1)CC2=CC=C(C=C2)C3=CC4=C(NC=C4C5=CC6=C(C=C5)NC=C6)N=C3
  InChI: InChI=1S/C27H27N5/c1-31-10-12-32(13-11-31)18-19-2-4-20(5-3-19)23-15-24-25(17-30-27(24)29-16-23)21-6-7-26-22(14-21)8-9-28-26/h2-9,14-17,28H,10-13,18H2,1H3,(H,29,30)
  InChIKey: QKKIWEILHCXECO-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 54764565
  TTD ID: D07ADX

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cyclin-dependent kinase-like 2 (CDKL2)	TTMO45N	CDKL2_HUMAN	Inhibitor	[1]
Death-associated protein kinase 3 (DAPK3)	TTERVQN	DAPK3_HUMAN	Inhibitor	[1]
Fms-like tyrosine kinase 3 (FLT-3)	TTGJCWZ	FLT3_HUMAN	Inhibitor	[1]
Leucine-rich repeat kinase 2 (LRRK2)	TTK0FEA	LRRK2_HUMAN	Inhibitor	[1]
MAPK/ERK kinase kinase 2 (MAP3K2)	TTK1N5G	M3K2_HUMAN	Inhibitor	[1]
Mixed lineage kinase 1 (MAP3K9)	TTUNSIX	M3K9_HUMAN	Inhibitor	[1]
Mixed lineage kinase 2 (MAP3K10)	TT9FN4J	M3K10_HUMAN	Inhibitor	[1]
Mixed lineage kinase 3 (MAP3K11)	TTETX6Q	M3K11_HUMAN	Inhibitor	[1]
SRSF protein kinase 2 (SRPK2)	TTCZEJ9	SRPK2_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
Fms-like tyrosine kinase 3 (FLT-3)	DTT	FLT3	2.11E-01	-0.05	-0.16

References

• [1] Discovery, synthesis, and characterization of an orally bioavailable, brain penetrant inhibitor of mixed lineage kinase 3. J Med Chem. 2013 Oct 24;56(20):8032-48.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Leucine-rich repeat kinase 2 inhibitors: a patent review (2014-2016).Expert Opin Ther Pat. 2017 Jun;27(6):667-676.
• [4] Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-linea... J Med Chem. 2008 Sep 25;51(18):5680-9.
• [5] Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
• [6] 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: 1807).
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [8] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [9] 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.
• [10] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [12] Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with ... Blood. 2008 Jun 15;111(12):5663-71.
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.