Midostaurin

Summary

Midostaurin (CHEMBL608533) is an approved small-molecule EC 2.7.11.13 (protein kinase C) inhibitor (ATC L01EX10) targeting LATS1, LATS2, and FLT3; indicated across 10 conditions including acute myeloid leukemia and neoplasm.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01EX10
• Targets: 3 (LATS1, LATS2, FLT3)
• Indications: 10 conditions
• Clinical trials: 46
• Chemistry: 570.6 Da · C35H30N4O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL608533
Name	Midostaurin
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	9829523
ChEBI	CHEBI:63452
ATC	L01EX10
Molecular formula	C35H30N4O4
Molecular weight	570.6
InChIKey	BMGQWWVMWDBQGC-IIFHNQTCSA-N

SMILES: C[C@@]12[C@@H]([C@@H](C[C@@H](O1)N3C4=CC=CC=C4C5=C6C(=C7C8=CC=CC=C8N2C7=C53)CNC6=O)N(C)C(=O)C9=CC=CC=C9)OC

IUPAC name: N-[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-N-methylbenzamide

ChEBI definition: An organic heterooctacyclic compound that is the N-benzoyl derivative of staurosporine.

Pharmacological roles (ChEBI): EC 2.7.11.13 (protein kinase C) inhibitor, antineoplastic agent.

Also known as: CGP 41251, CGP-41251, Midostaurin, Midostaurina, Midostaurine, N-benzoylstaurosporine, NSC-656576, NVP-PKC412, PKC 412, Pkc-412, PKC-412, Rydapt

Patent coverage: 3,040 distinct patent families (7,259 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 7,068 (97%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
LATS1	large tumor suppressor kinase 1	Inhibition	5.96	0.1%	O95835
LATS2	large tumor suppressor kinase 2	Inhibition	5.66	0.6%	Q9NRM7
FLT3	fms related receptor tyrosine kinase 3	Inhibition	6.28	0.9%	P36888

Broader ChEMBL bioactivity targets: 213 (assay-derived). Sample: Leucine-rich repeat serine/threonine-protein kinase 2, Rhodopsin kinase GRK7, Homeodomain-interacting protein kinase 4, Serine/threonine-protein kinase/endoribonuclease IRE1, Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma, Mitogen-activated protein kinase kinase kinase 13, Serine/threonine-protein kinase ICK, Microtubule-associated serine/threonine-protein kinase 1, Hormonally up-regulated neu tumor-associated kinase, Tyrosine-protein kinase Fyn.

Bioactivity

ChEMBL activities: 684 potent at pChembl ≥ 5 of 687 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
FLT3	9	IC50	1	nM	CHEMBL_ACT_24992747
FLT3	8.7	Kd	2	nM	CHEMBL_ACT_3448935
FLT3	8.7	Kd	2	nM	CHEMBL_ACT_7574226
FLT3	8.22	Kd	6	nM	CHEMBL_ACT_2890868
FLT3	8.22	Kd	6	nM	CHEMBL_ACT_3448936
FLT3	8.22	Kd	6	nM	CHEMBL_ACT_7574227
FLT3	8.17	Kd	6.8	nM	CHEMBL_ACT_19250401
FLT3	8.17	Kd	6.8	nM	CHEMBL_ACT_2907440
FLT3	8.17	Kd	6.8	nM	CHEMBL_ACT_3448932
FLT3	8.17	Kd	6.8	nM	CHEMBL_ACT_7574223
KIT	8.11	Kd	7.7	nM	CHEMBL_ACT_2896932
KIT	8.11	Kd	7.7	nM	CHEMBL_ACT_3448961
KIT	8.11	Kd	7.7	nM	CHEMBL_ACT_6220413
KIT	8.11	Kd	7.7	nM	CHEMBL_ACT_7574073
EGFR	8.06	Kd	8.8	nM	CHEMBL_ACT_7574292
PKN1	8.03	Kd	9.3	nM	CHEMBL_ACT_2905175
PKN1	8.03	Kd	9.3	nM	CHEMBL_ACT_3449015
TBK1	8.03	Kd	9.3	nM	CHEMBL_ACT_3449059
TBK1	8.03	Kd	9.3	nM	CHEMBL_ACT_7574362
PKN1	8.03	Kd	9.3	nM	CHEMBL_ACT_7576015
EGFR	8.01	Kd	9.8	nM	CHEMBL_ACT_7574295
FLT3	7.96	Kd	11	nM	CHEMBL_ACT_13476450
FLT3	7.96	Kd	11	nM	CHEMBL_ACT_19067237
FLT3	7.96	Kd	11	nM	CHEMBL_ACT_19250407
FLT3	7.96	Kd	11	nM	CHEMBL_ACT_19250425
FLT3	7.96	Kd	11	nM	CHEMBL_ACT_2890830
FLT3	7.96	Kd	11	nM	CHEMBL_ACT_2907402
FLT3	7.96	Kd	11	nM	CHEMBL_ACT_3446531
FLT3	7.96	Kd	11	nM	CHEMBL_ACT_3448931
FLT3	7.96	Kd	11	nM	CHEMBL_ACT_7574222

Target pathways

Aggregated over 3 target gene(s): LATS1, LATS2, FLT3.

Top Reactome pathways

29 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	2	LATS1, LATS2
Signaling by Hippo	2	LATS1, LATS2
PI3K Cascade	1	FLT3
PIP3 activates AKT signaling	1	FLT3
Constitutive Signaling by Aberrant PI3K in Cancer	1	FLT3
RAF/MAP kinase cascade	1	FLT3
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	FLT3
FLT3 Signaling	1	FLT3
STAT5 Activation	1	FLT3
FLT3 mutants bind TKIs	1	FLT3
STAT5 activation downstream of FLT3 ITD mutants	1	FLT3
KW2449-resistant FLT3 mutants	1	FLT3
semaxanib-resistant FLT3 mutants	1	FLT3
crenolanib-resistant FLT3 mutants	1	FLT3
gilteritinib-resistant FLT3 mutants	1	FLT3
lestaurtinib-resistant FLT3 mutants	1	FLT3
midostaurin-resistant FLT3 mutants	1	FLT3
pexidartinib-resistant FLT3 mutants	1	FLT3
ponatinib-resistant FLT3 mutants	1	FLT3
quizartinib-resistant FLT3 mutants	1	FLT3
sorafenib-resistant FLT3 mutants	1	FLT3
sunitinib-resistant FLT3 mutants	1	FLT3
tandutinib-resistant FLT3 mutants	1	FLT3
linifanib-resistant FLT3 mutants	1	FLT3
tamatinib-resistant FLT3 mutants	1	FLT3
Signaling by FLT3 ITD and TKD mutants	1	FLT3
Negative regulation of FLT3	1	FLT3
FLT3 signaling through SRC family kinases	1	FLT3
FLT3 signaling by CBL mutants	1	FLT3

Dominant GO biological processes

GO term	Targets
protein phosphorylation	3
G1/S transition of mitotic cell cycle	2
inner cell mass cell fate commitment	2
inner cell mass cellular morphogenesis	2
intracellular protein localization	2
hormone-mediated signaling pathway	2
regulation of transforming growth factor beta receptor signaling pathway	2
keratinocyte differentiation	2
hippo signaling	2
positive regulation of apoptotic process	2
negative regulation of cyclin-dependent protein serine/threonine kinase activity	2
regulation of organ growth	2
cell division	2
negative regulation of canonical Wnt signaling pathway	2
negative regulation of protein localization to nucleus	2

Indications & clinical

Indications

10 indications (5 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
acute myeloid leukemia	4	MONDO:0018874	EFO:0000222
neoplasm	4	MONDO:0005070	EFO:0000616
mast cell leukemia	4	MONDO:0020334	EFO:0007359
mastocytosis	4	MONDO:0007950	EFO:0009001
leukemia	3	MONDO:0005059	EFO:0000565
myelodysplastic syndrome	2	MONDO:0018881	EFO:0000198
liver disorder	1	MONDO:0005154	EFO:0001421
rectal cancer	1	MONDO:0006519	EFO:1000657
acute lymphoblastic leukemia	1	MONDO:0004967	EFO:0000220

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 46.

Phase distribution

Phase	Trials
PHASE2	16
PHASE1	12
PHASE1/PHASE2	7
PHASE3	6
Not specified	4
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04027309	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Gilteritinib Versus Midostaurin in Combination With Induction and Consolidation Therapy Followed by One-year Maintenance in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndromes With Excess Blasts-2 With FLT3 Mutations Eligible for Intensive Chemotherapy
NCT00651261	PHASE3	UNKNOWN	Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT03092674	PHASE2/PHASE3	COMPLETED	Azacitidine With or Without Nivolumab or Midostaurin, or Decitabine and Cytarabine Alone in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
NCT03258931	PHASE3	COMPLETED	Study of Crenolanib vs Midostaurin Following Induction Chemotherapy and Consolidation Therapy in Newly Diagnosed FLT3 Mutated AML
NCT03379727	PHASE3	COMPLETED	Study to Assess the Safety and Efficacy of Midostaurin (PKC412) in Combination With Standard Chemotherapy During Induction and Consolidation Followed by 12 Months of Maintenance Monotherapy in Patients With Newly-diagnosed FMS-like Tyrosine 3 (FLT3) Kinase Receptor-mutated Acute Myeloid Leukemia.
NCT03512197	PHASE3	COMPLETED	A Global Study of the Efficacy and Safety of Midostaurin + Chemotherapy in Newly Diagnosed Patients With FLT3 Mutation Negative (FLT3-MN) Acute Myeloid Leukemia (AML)
NCT04174612	PHASE3	UNKNOWN	AML Patients Bearing FLT3 Mutations Based on Peripheral Blast Clearance
NCT02115295	PHASE2	RECRUITING	Cladribine, Idarubicin, Cytarabine, and Venetoclax in Treating Patients With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome, or Blastic Phase Chronic Myeloid Leukemia
NCT03591510	PHASE2	ACTIVE_NOT_RECRUITING	A Global Study of Midostaurin in Combination With Chemotherapy to Evaluate Safety, Efficacy and Pharmacokinetics in Newly Diagnosed Pediatric Patients With FLT3 Mutated AML
NCT03836209	PHASE2	ACTIVE_NOT_RECRUITING	Gilteritinib vs Midostaurin in FLT3 Mutated Acute Myeloid Leukemia
NCT04097470	PHASE2	ACTIVE_NOT_RECRUITING	Tolerability and Efficacy of Midostaurin to 10-day Decitabine in Unfit Adult AML and High Risk MDS Patients
NCT04385290	PHASE1/PHASE2	RECRUITING	Combination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)
NCT00045942	PHASE1/PHASE2	COMPLETED	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)
NCT00233454	PHASE2	COMPLETED	Phase 2 Midostaurin in Aggressive Systemic Mastocytosis and Mast Cell Leukemia
NCT00782067	PHASE2	COMPLETED	Efficacy and Safety of Midostaurin in Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia
NCT00866281	PHASE1/PHASE2	TERMINATED	A Study of the Safety and Preliminary Efficacy of Oral Midostaurin (PKC412) in Relapsed or Refractory Pediatric Leukemia
NCT01093573	PHASE1/PHASE2	COMPLETED	Midostaurin and Azacitidine in Treating Elderly Patients With Acute Myelogenous Leukemia
NCT01202877	PHASE1/PHASE2	COMPLETED	PKC412 and 5-Azacytidine
NCT01477606	PHASE2	COMPLETED	Protocol in Acute Myeloid Leukemia With FLT3-ITD
NCT01830361	PHASE2	COMPLETED	Trial to Assess the Efficacy of Midostaurin (PKC412) in Patients With c-KIT or FLT3-ITD Mutated t(8;21) AML
NCT01846624	PHASE2	TERMINATED	Decitabine and Midostaurin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT01883362	PHASE2	COMPLETED	Standard of Care +/- Midostaurin to Prevent Relapse Post Stem Cell Transplant in Patients With FLT3-ITD Mutated AML
NCT02634827	PHASE2	TERMINATED	Midostaurin and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia and FLT3 Mutation
NCT02723435	PHASE2	WITHDRAWN	Midostaurin in Treating Older Patients With Mutated Acute Myeloid Leukemia Post-Transplant
NCT03207334	PHASE2	WITHDRAWN	iCare4: Genomic Signatures With Midostaurin in Acute Myeloid Leukemia (UF-HEM-004)
NCT03280030	PHASE2	COMPLETED	A Study of Midostaurin Efficacy and Safety in Newly Diagnosed Patients With FLT3-mutated AML
NCT03686345	PHASE2	TERMINATED	Midostaurin Associated With Standard Chemotherapy in Patients With Core-binding Factor Leukemia
NCT03760445	PHASE1/PHASE2	WITHDRAWN	HDM201 Added to CT in R/R or Newly Diagnosed AML
NCT03951961	PHASE2	TERMINATED	Midostaurin in MRD (Minimal Residual Disease) Positive Acute Myeloid Leukemia After Allogeneic Stem Cell Transplantation
NCT04982354	PHASE1/PHASE2	WITHDRAWN	Induction Therapy for Patients With FLT3 Mutated Acute Myeloid Leukemia
NCT00819546	PHASE1	ACTIVE_NOT_RECRUITING	RAD001 in Combination With PKC412 in Patients With Relapsed, Refractory or Poor Prognosis AML or MDS
NCT06313437	PHASE1	RECRUITING	Revumenib in Combination With 7+3 + Midostaurin in AML
NCT00093600	PHASE1	COMPLETED	PKC412, Daunorubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT01130662	PHASE1	COMPLETED	Combination of Decitabine and Midostaurin in Patients Older Than 60 With Newly Diagnosed or Relapsed Refractory Acute Myeloid Leukemia
NCT01161550	PHASE1	COMPLETED	Cladribine Based Induction Therapy With All-Trans Retinoic Acid and Midostaurin in Relapsed/Refractory AML
NCT01174888	PHASE1	COMPLETED	Phase I Combination of Midostaurin, Bortezomib, and Chemo in Relapsed/Refractory Acute Myeloid Leukemia
NCT01282502	PHASE1	COMPLETED	Midostaurin (PKC412) for Locally Advanced Rectal Cancer
NCT01429337	PHASE1	COMPLETED	PK and Safety of Midostaurin in Subjects With Impaired Hepatic Function and Subjects With Normal Hepatic Function
NCT02078609	PHASE1	COMPLETED	A Safety and Efficacy Study of LGH447 in Patients With Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)
NCT03900949	PHASE1	COMPLETED	Gentuzumab Ozogamicin and Midostaurin Combination With Standard Cytarabine and Danunorubi Midostaurin as a Novel Approach to Treating Patients With Newly Diagnosed FLT-3 Mutated Acute Myeloid Leukemia

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

145 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
Afatinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1, LATS2
Axitinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1, LATS2
Bosutinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1, LATS2
Crizotinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1, LATS2
Erlotinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1, LATS2
Fedratinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1, LATS2
Gefitinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1, LATS2
Imatinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1, LATS2
Neratinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1, LATS2
Nilotinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1, LATS2
Pazopanib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1, LATS2
Quizartinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1, LATS2
Sorafenib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1, LATS2
SUNITINIB	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1, LATS2
Vandetanib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1, LATS2
NINTEDANIB	ChEMBL	Phase 4 (approved)	FLT3, LATS1, LATS2
DOVITINIB	ChEMBL	Phase 3	FLT3, LATS1, LATS2
LESTAURTINIB	ChEMBL	Phase 3	FLT3, LATS1, LATS2
LINIFANIB	ChEMBL	Phase 3	FLT3, LATS1, LATS2
RUBOXISTAURIN	ChEMBL	Phase 3	FLT3, LATS1, LATS2
SU-014813	ChEMBL	Phase 2	FLT3, LATS1, LATS2
TG100-115	ChEMBL	Phase 2	FLT3, LATS1, LATS2
TOZASERTIB	ChEMBL	Phase 2	FLT3, LATS1, LATS2
Idelalisib	PubChem	Approved	FLT3, LATS1, LATS2
Selumetinib	PubChem	Approved	FLT3, LATS1, LATS2
Abemaciclib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1
Cabozantinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1
Ceritinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1
Entrectinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1
FOSTAMATINIB	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1
GILTERITINIB	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1
IBRUTINIB	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1
Pacritinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1
Palbociclib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1
Pexidartinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1
Ponatinib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1
Tivozanib	ChEMBL + PubChem	Phase 4 (approved)	FLT3, LATS1
CRENOLANIB	ChEMBL	Phase 3	FLT3, LATS1
DEFACTINIB	ChEMBL	Phase 3	FLT3, LATS1
LINSITINIB	ChEMBL	Phase 3	FLT3, LATS1
ORANTINIB	ChEMBL	Phase 3	FLT3, LATS1
AT-9283	ChEMBL	Phase 2	FLT3, LATS1
MILCICLIB	ChEMBL	Phase 2	FLT3, LATS1
R-406	ChEMBL	Phase 2	FLT3, LATS2
Acalabrutinib	PubChem	Approved	LATS1, LATS2
Binimetinib	PubChem	Approved	FLT3, LATS1
dacomitinib	PubChem	Approved	FLT3, LATS1
Duvelisib	PubChem	Approved	LATS1, LATS2
Lapatinib	PubChem	Approved	LATS1, LATS2
Ruxolitinib	PubChem	Approved	LATS1, LATS2
Tofacitinib	PubChem	Approved	LATS1, LATS2
Trametinib	PubChem	Approved	FLT3, LATS1
CAPIVASERTIB	ChEMBL + PubChem	Phase 4 (approved)	LATS1
BRIGATINIB	ChEMBL	Phase 4 (approved)	FLT3
DASATINIB	ChEMBL	Phase 4 (approved)	FLT3
FILGOTINIB	ChEMBL	Phase 4 (approved)	FLT3
INFIGRATINIB	ChEMBL	Phase 4 (approved)	FLT3
PRALSETINIB	ChEMBL	Phase 4 (approved)	FLT3
ALVOCIDIB	ChEMBL	Phase 3	FLT3