Details of the Drug Combination

General Information of Drug Combination (ID: DCIZZQS)

• Drug Combination Name: ABT-199 + Abexinostat
• Indication: Diffuse intrinsic pontine glioma; Status: Investigative [1]
• Component Drugs:
  ABT-199 (DM2BLMT): N.A.
  Abexinostat (DM91LGU): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DIPG25
  Zero Interaction Potency (ZIP) Score: 32.521
  Bliss Independence Score: 28.347
  Loewe Additivity Score: 13.782
  LHighest Single Agent (HSA) Score: 29.691

Molecular Interaction Atlas of This Drug Combination

Indication(s) of ABT-199

Disease Entry	ICD 11	Status	REF
Chronic lymphocytic leukaemia	2A82.0	Phase 3	[2]

Indication(s) of Abexinostat

Disease Entry	ICD 11	Status	REF
Follicular lymphoma	2A80	Phase 3	[3]
Renal cell carcinoma	2C90	Phase 3	[4]
Acute myeloid leukaemia	2A60	Phase 2	[3]
Breast cancer	2C60-2C65	Phase 2	[3]
Diffuse large B-cell lymphoma	2A81	Phase 2	[3]
Gynecologic cancer	2F33-2F76	Phase 2	[3]
Peripheral T-cell lymphoma	2A90.C	Phase 2	[3]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]

Abexinostat Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Histone deacetylase (HDAC)	TTBH0VX	NOUNIPROTAC	Modulator	[6]

Abexinostat Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB)	OT9RDS3H	IKKB_HUMAN	Decreases Expression	[5]
Growth arrest and DNA damage-inducible protein GADD45 gamma (GADD45G)	OT8V1J4M	GA45G_HUMAN	Increases Expression	[7]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[5]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[5]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[7]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Decreases Expression	[5]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[5]
Heme oxygenase 2 (HMOX2)	OTG40XBT	HMOX2_HUMAN	Decreases Expression	[5]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[5]
Breast cancer type 2 susceptibility protein (BRCA2)	OTF1XSV1	BRCA2_HUMAN	Decreases Expression	[7]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[5]
C-C motif chemokine 7 (CCL7)	OTDIS99H	CCL7_HUMAN	Decreases Expression	[5]
Transcription factor RelB (RELB)	OTU3QYEF	RELB_HUMAN	Decreases Expression	[5]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Decreases Expression	[7]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Cleavage	[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] Clinical pipeline report, company report or official report of Abbott Laboratories.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] ClinicalTrials.gov (NCT03592472) A Study of Pazopanib With or Without Abexinostat in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma (RENAVIV). U.S. National Institutes of Health.
• [5] PCI-24781 induces caspase and reactive oxygen species-dependent apoptosis through NF-kappaB mechanisms and is synergistic with bortezomib in lymphoma cells. Clin Cancer Res. 2009 May 15;15(10):3354-65. doi: 10.1158/1078-0432.CCR-08-2365. Epub 2009 May 5.
• [6] Phase 1 study of the oral histone deacetylase inhibitor abexinostat in patients with Hodgkin lymphoma, non-Hodgkin lymphoma, or chronic lymphocytic leukaemia. Invest New Drugs. 2015 Apr;33(2):423-31.
• [7] HDAC inhibitor PCI-24781 decreases RAD51 expression and inhibits homologous recombination. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19482-7. doi: 10.1073/pnas.0707828104. Epub 2007 Nov 27.