Details of the Drug

General Information of Drug (ID: DMGCX7E)

• Drug Name: 9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione
• Synonyms: CHEMBL209907; 9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione; SCHEMBL5829446; IJHAYZZOYYQESB-UHFFFAOYSA-N; BDBM50192426

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); 252.22
  Topological Polar Surface Area (xlogp); 1.8
  Rotatable Bond Count (rotbonds); 0
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 3
• Chemical Identifiers:
  Formula: C14H8N2O3
  IUPAC Name: 9-hydroxy-6H-pyrrolo[3,4-c]carbazole-1,3-dione
  Canonical SMILES: C1=CC2=C(C=C1O)C3=C(N2)C=CC4=C3C(=O)NC4=O
  InChI: InChI=1S/C14H8N2O3/c17-6-1-3-9-8(5-6)11-10(15-9)4-2-7-12(11)14(19)16-13(7)18/h1-5,15,17H,(H,16,18,19)
  InChIKey: IJHAYZZOYYQESB-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 11844342
  TTD ID: D0Y3PH

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Checkpoint kinase-1 (CHK1)	TTTU902	CHK1_HUMAN	Inhibitor	[2]
Wee1-like protein kinase (WEE1)	TTJFOAL	WEE1_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
Checkpoint kinase-1 (CHK1)	DTT	CHEK1	7.22E-191	1.43	4.74

References

• [1] Receptor-based 3D-QSAR studies of checkpoint Wee1 kinase inhibitors. Eur J Med Chem. 2009 Apr;44(4):1383-95.
• [2] 4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione inhibitors of the checkpoint kinase Wee1. Structure-activity relationships for chromophore modific... J Med Chem. 2006 Aug 10;49(16):4896-911.
• [3] Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs. 2014 Apr;32(2):213-26.
• [4] Characterization of an inhibitory dynamic pharmacophore for the ERCC1-XPA interaction using a combined molecular dynamics and virtual screening app... J Mol Graph Model. 2009 Sep;28(2):113-30.
• [5] Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. Mol Cancer Ther. 2011 Apr;10(4):591-602.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] A phase Ib study of oral Chk1 inhibitor LY2880070 in combination with gemcitabine in patients with advanced or metastatic cancer. Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 3581-3581.
• [8] National Cancer Institute Drug Dictionary (drug id 730054).
• [9] Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199).
• [10] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [11] Chk1 Inhibitor MK-8776 Restores the Sensitivity of Chemotherapeutics in P-glycoprotein Overexpressing Cancer Cells. Int J Mol Sci. 2019 Aug 22;20(17):4095.
• [12] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [13] A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
• [14] Clinical pipeline report, company report or official report of Zentalis Pharmaceuticals.