Details of the Drug Combination

General Information of Drug Combination (ID: DCA8G0K)

• Drug Combination Name: K-134 + ML323
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  K-134 (DMD4OK0): Small molecular drug
  ML323 (DMY91A3): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 57.79
  Bliss Independence Score: 57.79
  Loewe Additivity Score: 70.65
  LHighest Single Agent (HSA) Score: 70.65

Molecular Interaction Atlas of This Drug Combination

Indication(s) of K-134

Disease Entry	ICD 11	Status	REF
Arteriosclerosis	BD40	Phase 2	[2]

K-134 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Phosphodiesterase 3 (PDE3)	TTZCG4L	NOUNIPROTAC	Modulator	[4]

Indication(s) of ML323

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Preclinical	[3]

ML323 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Deubiquitinating enzyme 1 (USP1)	TTG9MT5	UBP1_HUMAN	Inhibitor	[5]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] ClinicalTrials.gov (NCT00783081) Safety and Efficacy of K-134 for the Treatment of Intermittent Claudication. U.S. National Institutes of Health.
• [3] Deubiquitylating enzymes and drug discovery: emerging opportunities. Nat Rev Drug Discov. 2018 Jan;17(1):57-78.
• [4] A phase II dose-ranging study of the phosphodiesterase inhibitor K-134 in patients with peripheral artery disease and claudication. J Vasc Surg. 2012 Feb;55(2):381-389.e1.
• [5] Synthesis and structure-activity relationship studies of N-benzyl-2-phenylpyrimidin-4-amine derivatives as potent USP1/UAF1 deubiquitinase inhibitors with anticancer activity against nonsmall cell lung cancer. J Med Chem. 2014 Oct 9;57(19):8099-110.