Details of the Drug

General Information of Drug (ID: DMNB4XK)

• Drug Name: BVD-523

Indication

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Phase 2	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[2]
Pancreatic cancer	2C10	Phase 1	[3]

• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 433.3
  Topological Polar Surface Area (xlogp); 4.1
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 4
• Chemical Identifiers:
  Formula: C21H22Cl2N4O2
  IUPAC Name: N-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-4-[5-chloro-2-(propan-2-ylamino)pyridin-4-yl]-1H-pyrrole-2-carboxamide
  Canonical SMILES: CC(C)NC1=NC=C(C(=C1)C2=CNC(=C2)C(=O)N[C@H](CO)C3=CC(=CC=C3)Cl)Cl
  InChI: InChI=1S/C21H22Cl2N4O2/c1-12(2)26-20-8-16(17(23)10-25-20)14-7-18(24-9-14)21(29)27-19(11-28)13-4-3-5-15(22)6-13/h3-10,12,19,24,28H,11H2,1-2H3,(H,25,26)(H,27,29)/t19-/m1/s1
  InChIKey: KSERXGMCDHOLSS-LJQANCHMSA-N
• Cross-matching ID:
  PubChem CID: 11719003
  CAS Number: 869886-67-9
  TTD ID: D01IED

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Ephrin type-B receptor 2 (EPHB2)	TTKPV6O	EPHB2_HUMAN	Inhibitor	[3]
Extracellular signal-regulated kinase 1 (ERK1)	TT1MG9E	MK03_HUMAN	Modulator	[4]
Extracellular signal-regulated kinase 2 (ERK2)	TT4TQBX	MK01_HUMAN	Modulator	[4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Melanoma
• ICD Disease Classification: 2C30

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Extracellular signal-regulated kinase 2 (ERK2)	DTT	MAPK1	6.78E-05	1.12	2.73

References

• [1] ClinicalTrials.gov (NCT03417739) A Phase II Study of BVD-523 in Metastatic Uveal Melanoma. U.S. National Institutes of Health.
• [2] ClinicalTrials.gov (NCT01781429) Phase I Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients With Advanced Malignancies. U.S. National Institutes of Health.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] DOI: 10.1158/1538-7445.AM2015-4693
• [5] Clinical pipeline report, company report or official report of HaiHe Biopharma.
• [6] Clinical pipeline report, company report or official report of Astex Pharmaceuticals.
• [7] WO patent application no. 2013,1850,32, Nanotherapeutics for drug targeting.
• [8] ERK Mutations Confer Resistance to Mitogen-Activated Protein Kinase Pathway Inhibitors
• [9] National Cancer Institute Drug Dictionary (drug name JSI1187).
• [10] Corchorusin-D directed apoptosis of K562 cells occurs through activation of mitochondrial and death receptor pathways and suppression of AKT/PKB pathway. Cell Physiol Biochem. 2012;30(4):915-26.
• [11] Synthesis and biological testing of purine derivatives as potential ATP-competitive kinase inhibitors. J Med Chem. 2005 Feb 10;48(3):710-22.
• [12] Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.
• [13] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [14] Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
• [15] National Cancer Institute Drug Dictionary (drug name SEphB4-HSA).
• [16] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [17] Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J Med Chem. 2013 Apr 11;56(7):2936-47.
• [18] Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4). J Med Chem. 2009 Oct 22;52(20):6433-46.
• [19] Three-dimensional structure of the EphB2 receptor in complex with an antagonistic peptide reveals a novel mode of inhibition. J Biol Chem. 2007 Dec 14;282(50):36505-13.