Details of the Drug Combination

General Information of Drug Combination (ID: DCMYOIZ)

• Drug Combination Name: BIO-300 + Bendamustine hydrochloride
• Indication: Adult T acute lymphoblastic leukemia; Status: Investigative [1]
• Component Drugs:
  BIO-300 (DMJ7NVI): N.A.
  Bendamustine hydrochloride (DMFH15Z): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: MOLT-4
  Zero Interaction Potency (ZIP) Score: 3.74
  Bliss Independence Score: 3.02
  Loewe Additivity Score: 1.75
  LHighest Single Agent (HSA) Score: 4.45

Molecular Interaction Atlas of This Drug Combination

Indication(s) of BIO-300

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[2]
Rheumatoid arthritis	FA20	Phase 1	[3]

Indication(s) of Bendamustine hydrochloride

Disease Entry	ICD 11	Status	REF
leukaemia	2A60-2B33	Approved	[4]

Bendamustine hydrochloride Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[4]

Bendamustine hydrochloride Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[6]

Bendamustine hydrochloride Interacts with 13 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[5]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[5]
Beta-galactosidase (GLB1)	OTB0TKAG	BGAL_HUMAN	Increases Expression	[7]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[5]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[5]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[5]
Caspase-6 (CASP6)	OTXLD3EC	CASP6_HUMAN	Increases Activity	[5]
Baculoviral IAP repeat-containing protein 3 (BIRC3)	OT3E95KB	BIRC3_HUMAN	Decreases Expression	[5]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Expression	[8]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[5]
PRKC apoptosis WT1 regulator protein (PAWR)	OTKY7W52	PAWR_HUMAN	Decreases Expression	[5]
Diablo IAP-binding mitochondrial protein (DIABLO)	OTHJ9MCZ	DBLOH_HUMAN	Increases Localization	[5]
Death domain-associated protein 6 (DAXX)	OTX6O7PL	DAXX_HUMAN	Decreases Expression	[5]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Anaplastic large cell lymphoma	DC8J3L7	SR	Investigative	[1]
Astrocytoma	DC03HBQ	SNB-19	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCD71RM	CCRF-CEM	Investigative	[1]
Chronic myelogenous leukemia	DCT6R7A	K-562	Investigative	[1]
Glioma	DC7RL2B	SF-539	Investigative	[1]
Glioma	DCPD8LK	SF-268	Investigative	[1]
Papillary renal cell carcinoma	DCLWPYT	ACHN	Investigative	[1]
Plasma cell myeloma	DCDD94C	RPMI-8226	Investigative	[1]
Renal cell carcinoma	DCZBXNF	UO-31	Investigative	[1]
Breast adenocarcinoma	DC6LYSZ	MDA-MB-468	Investigative	[9]
Carcinoma	DCKAVL0	RXF 393	Investigative	[9]
Colon adenocarcinoma	DC695SI	COLO 205	Investigative	[9]
Invasive ductal carcinoma	DCWD8MG	HS 578T	Investigative	[9]
Invasive ductal carcinoma	DCTPF96	BT-549	Investigative	[9]
Adenocarcinoma	DCUUA2Q	DU-145	Investigative	[10]
Adenocarcinoma	DCPSVKC	OVCAR3	Investigative	[10]
Adenocarcinoma	DCTI5RQ	NCIH23	Investigative	[10]
Adenocarcinoma	DC6BYV9	A549	Investigative	[10]
Adenocarcinoma	DCP9C07	SW-620	Investigative	[10]
Adenocarcinoma	DCRXGG7	HCT116	Investigative	[10]
Adenocarcinoma	DCCIQPG	HCC-2998	Investigative	[10]
Adenocarcinoma	DC9PG7A	HCT-15	Investigative	[10]
Adenocarcinoma	DCYUDI0	HT29	Investigative	[10]
Cutaneous melanoma	DCZGLTG	SK-MEL-28	Investigative	[10]
High grade ovarian serous adenocarcinoma	DCEHGSK	OVCAR-5	Investigative	[10]
High grade ovarian serous adenocarcinoma	DC7UDR7	OVCAR-4	Investigative	[10]
High grade ovarian serous adenocarcinoma	DCR1YRN	OVCAR-8	Investigative	[10]
Large cell lung carcinoma	DCBZVS8	NCI-H460	Investigative	[10]
Lung adenocarcinoma	DCZIBN3	NCI-H522	Investigative	[10]
Melanoma	DCKW0CO	MALME-3M	Investigative	[10]
Minimally invasive lung adenocarcinoma	DCIADZT	NCI-H322M	Investigative	[10]
Prostate carcinoma	DCNSDSE	PC-3	Investigative	[10]

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 Humanetics.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [5] Synergistic effects of chemotherapeutic drugs in lymphoma cells are associated with down-regulation of inhibitor of apoptosis proteins (IAPs), prostate-apoptosis-response-gene 4 (Par-4), death-associated protein (Daxx) and with enforced caspase activation. Biochem Pharmacol. 2003 Sep 1;66(5):711-24. doi: 10.1016/s0006-2952(03)00410-6.
• [6] Pharmacokinetic and pharmacodynamic profile of bendamustine and its metabolites. Cancer Chemother Pharmacol. 2015 Jun;75(6):1143-54.
• [7] Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard. Arch Toxicol. 2021 Feb;95(2):727-747. doi: 10.1007/s00204-020-02946-5. Epub 2021 Jan 25.
• [8] Upon drug-induced apoptosis in lymphoma cells X-linked inhibitor of apoptosis (XIAP) translocates from the cytosol to the nucleus. Leuk Lymphoma. 2004 Jul;45(7):1429-36. doi: 10.1080/1042819042000198858.
• [9] Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
• [10] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.