Details of the Drug Combinations

General Information of This Drug (ID: DMI6E0R)

• Drug Name: Midostaurin (DMI6E0R)
• Synonyms: PKC412; 120685-11-2; Cgp 41251; 4'-N-Benzoylstaurosporine; CGP-41251; Benzoylstaurosporine; PKC-412; RYDAPT; PKC 412; UNII-ID912S5VON; N-Benzoylstaurosporine; ID912S5VON; CHEMBL608533; CHEBI:63452; Cgp 41 251; N-[(5S,6R,7R,9R)-6-methoxy-5-methyl-14-oxo-6,7,8,9,15,16-hexahydro-5H,14H-5,9-epoxy-4b,9a,15-triazadibenzo[b,h]cyclonona[1,2,3,4-jkl]cyclopenta[e]-as-indacen-7-yl]-N-methylbenzamide; PKC-412(Midostaurin); Midostaurin (PKC412); Midostaurin (USAN/INN); Midostaurin [USAN:INN]; CGP 41231; Rydapt (TN); CPG 41251

Indication

Acute myeloid leukaemia; ICD 11: 2A60; Status: Approved [1]; Systemic mastocytosis; ICD 11: 2A21.0; Status: Approved [2]; Chronic myelomonocytic leukaemia; ICD 11: 2A40; Status: Phase 2 [3]; Colorectal cancer; ICD 11: 2B91.Z; Status: Phase 1 [3]

• Therapeutic Class: Anticancer Agents
• Drug Type: Small molecular drug

List of Combinatorial Drugs (CBD) Containing This Drug

20 Investigative Drug Combination(s) Consisting of This drug

Normalized Drug Combination Synergy Score

Synergy scores were normalized using Min-Max Scaling to facilitate visual comparisons.

DrugCom Name	DrugCom ID	Component Drug	Indication	REF
Gentian violet + Midostaurin	DCNQOVD	Gentian violet	Hepatoblastoma (Cell Line: HB3)	[4]
Midostaurin + Ruxolitinib	DCP5M72	Ruxolitinib	T-cell leukemia/lymphoma (Cell Line: ED-40515)	[5]
Midostaurin + Artemether	DCI262X	Artemether	DD2 (Cell Line: DD2)	[5]
Midostaurin + Panobinostat	DCKAZ65	Panobinostat	DD2 (Cell Line: DD2)	[5]
Midostaurin + Panobinostat	DCIOGMC	Panobinostat	Diffuse intrinsic pontine glioma (Cell Line: DIPG25)	[5]
Midostaurin + Methylene blue	DCTLN8G	Methylene blue	DD2 (Cell Line: DD2)	[5]
Midostaurin + NITD609	DCK0CRB	NITD609	DD2 (Cell Line: DD2)	[5]
Midostaurin + Naltrexone	DCUVUAP	Naltrexone	DD2 (Cell Line: DD2)	[5]
Midostaurin + Piperaquine	DCJ3LJ7	Piperaquine	DD2 (Cell Line: DD2)	[5]
Midostaurin + Mefloquine	DCVVVOY	Mefloquine	DD2 (Cell Line: DD2)	[5]
Midostaurin + Atovaquone	DCNZBXO	Atovaquone	DD2 (Cell Line: DD2)	[5]
Midostaurin + Ibrutinib	DCZHSVE	Ibrutinib	Diffuse large B cell lymphoma (Cell Line: TMD8)	[5]
Midostaurin + Lumefantrine	DCQWNLF	Lumefantrine	Hepatoblastoma (Cell Line: HB3)	[4]
Midostaurin + Methylene blue	DC5LGQO	Methylene blue	Hepatoblastoma (Cell Line: HB3)	[4]
Midostaurin + Piperaquine	DCSFOHC	Piperaquine	Hepatoblastoma (Cell Line: HB3)	[4]
Midostaurin + Mefloquine	DC40MCL	Mefloquine	Hepatoblastoma (Cell Line: HB3)	[4]
Midostaurin + GDC-0077	DC98PXJ	GDC-0077	Hepatoblastoma (Cell Line: HB3)	[4]
Sitosterol + Midostaurin	DC0A0SI	Sitosterol	Hepatoblastoma (Cell Line: HB3)	[4]
Tranylcypromine + Midostaurin	DC6P5L0	Tranylcypromine	Hepatoblastoma (Cell Line: HB3)	[5]
Trichostatin A + Midostaurin	DCGZBDC	Trichostatin A	DD2 (Cell Line: DD2)	[5]

10 Clinical Trial Drug Combination(s) Consisting of This drug

DrugCom Name	DrugCom ID	Component Drug	Indication	REF
Everolimus + Midostaurin	DCP8Q16	Everolimus	Acute Myeloid Leukemia	[6]
Itraconazole + Midostaurin	DC69NA5	Itraconazole	Acute Myeloid Leukemia	[7]
Midostaurin + Bortezomib	DC0QYJM	Bortezomib	Acute Myeloid Leukemia	[8]
Midostaurin + Azacitidine	DCT8IBJ	Azacitidine	Untreated Adult Acute Myeloid Leukemia	[9]
Midostaurin + Daunorubicin	DCGGLSN	Daunorubicin	Acute Myeloid Leukemia	[10]
Midostaurin + Decitabine	DC5R3WF	Decitabine	Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in Adults	[11]
Midostaurin + Cytarabine	DC88VKZ	Cytarabine	Acute Myeloid Leukemia	[12]
Midostaurin + Decitabine	DCSY7P4	Decitabine	AML/MDS	[13]
Dexamethasone + Midostaurin	DCFH041	Dexamethasone	Leukemia	[14]
Midostaurin + Daunorubicin	DCAV7KA	Daunorubicin	Acute Myeloid Leukemia With FLT3/ITD Mutation	[15]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2018
• [2] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5702).
• [4] 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.
• [5] 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.
• [6] ClinicalTrials.gov (NCT00819546) RAD001 in Combination With PKC412 in Patients With Relapsed, Refractory or Poor Prognosis AML or MDS
• [7] ClinicalTrials.gov (NCT00045942) PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinase 3 (FLT3) (CPKC412A2104E1 and CPKC412A2104E2)
• [8] ClinicalTrials.gov (NCT01174888) Phase I Combination of Midostaurin, Bortezomib, and Chemo in Relapsed/Refractory Acute Myeloid Leukemia
• [9] ClinicalTrials.gov (NCT01093573) Midostaurin and Azacitidine in Treating Elderly Patients With Acute Myelogenous Leukemia
• [10] ClinicalTrials.gov (NCT03836209) Gilteritinib vs Midostaurin in FLT3 Mutated Acute Myeloid Leukemia
• [11] ClinicalTrials.gov (NCT01846624) Decitabine and Midostaurin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia
• [12] ClinicalTrials.gov (NCT03207334) iCare4: Genomic Signatures With Midostaurin in Acute Myeloid Leukemia (UF-HEM-004)
• [13] ClinicalTrials.gov (NCT04097470) Tolerability and Efficacy of Midostaurin to 10-day Decitabine in Unfit Adult AML and High Risk MDS Patients
• [14] ClinicalTrials.gov (NCT00651261) Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
• [15] ClinicalTrials.gov (NCT04174612) AML Patients Bearing FLT3 Mutations Based on Peripheral Blast Clearance