midostaurin

Trade name: rydapt

Small moleculeapprovedOrphan Drug ^FDAFast Track ^FDABreakthrough Therapy ^FDA

Approved

Apr 28, 2017

Midostaurin, a derivate of staurosporine (N-benzoylstaurosporine), is a broad-spectrum inhibitor of Ser/Thr and Tyr protein kinases. Midostaurin showed broad antiproliferative activity against various tumor and normal cell lines in vitro and is able to reverse the p-glycoprotein-mediated multidrug resistance of tumor cells in vitro. Midostaurin showed in vivo antitumor activity as single agent and inhibited angiogenesis in vivo. At the end of 2016 FDA granted Priority Review to the PKC412 (midostaurin) new drug application (NDA) for the treatment of acute myeloid leukemia (AML) in newly-diagnosed adults with an FMS-like tyrosine kinase-3 (FLT3) mutation, as well as for the treatment of advanced systemic mastocytosis (SM). — NCATS

Clinical trial activity

45 trials · 40 clinical orgs · 6 marketing orgs

Phase 1

Phase 2

Phase 3

Phase 4

Earliest trial started Jan 1, 2002 (NCT00045942)

Timeline

2000s

Jan 1, 2002
Novartis — Earliest Phase 2 Sponsor(trial)
Jan 1, 2004
Novartis — Earliest Phase 1 Sponsor(trial)
Jan 1, 2008
Earliest Phase 3 Sponsor(trial)
Jul 7, 2009
Orphan Drug Designation

2010s

Apr 28, 2017
Novartis — Earliest FDA Approval
Apr 28, 2017
Novartis — NDA Secondary Org
Apr 28, 2017
Novartis — Marketing Organization
Apr 28, 2017
Novartis — NDA Organization

2020s

Aug 24, 2022
Lotus Pharmaceutical — Marketing Organization
Aug 24, 2022
Alvogen — Marketing Organization
Apr 29, 2024
Teva — Marketing Organization
May 10, 2024
Lupin — Marketing Organization
Jun 28, 2024
Dr. Reddy's Laboratories — Marketing Organization

Indications

Approved for

Studied for

Mechanism of action

Protein kinase C (PKC)INHIBITOR
Protein kinase C (PKC) inhibitor
Multi-kinase inhibitor
Platelet-derived growth factor receptorINHIBITOR
Platelet-derived growth factor receptor inhibitor
Multi-kinase inhibitor
- Platelet-derived growth factor receptor beta (PDGFRB) ↗
- Platelet-derived growth factor receptor alpha (PDGFRA) ↗
- Platelet-derived growth factor receptor beta
- Platelet-derived growth factor receptor alpha
Tyrosine-protein kinase receptor FLT3INHIBITOR
FLT3 inhibitor
Multi-kinase inhibitor
- Receptor-type tyrosine-protein kinase FLT3 (FLT3) ↗
Stem cell growth factor receptorINHIBITOR
KIT inhibitor
Multi-kinase inhibitor
- Mast/stem cell growth factor receptor Kit (KIT) ↗
Vascular endothelial growth factor receptor 2INHIBITOR
KDR inhibitor
Multi-kinase inhibitor
- Vascular endothelial growth factor receptor 2 (KDR) ↗

Approval history

approvedPriority reviewFast trackBreakthroughApr 28, 2017

Chemistry & pharmacology

Loading structure…

SMILES

CO[C@@H]1[C@@H](C[C@H]2O[C@]1(C)n3c4ccccc4c5c6CNC(=O)c6c7c8ccccc8n2c7c35)N(C)C(=O)C9=CC=CC=C9

Mol. weight: 570.6371 g/mol
Lipinski Ro5: 2 violation(s)
Rule of 3: No
Chirality: Single Stereoisomer
Inorganic: No
Polymer: No
Delivery: Oral
Availability: Prescription Only

Oral

Yes

Parenteral

Topical

First in class

Sources

Also known as

4'-n-benzoylstaurosporine
4'-n-benzoylstaurosporine
4'-n-benzoylstaurosporine
4'-n-benzoyl staurosporine
benzamide, n-(2,3,9,10,11,12-hexahydro-9-methoxy-8-methyl-1-oxo-8,12-epoxy-1h,8h-2,7b,12a-triazadibenzo(a,g)cyclonona(cde)trinden-10-yl)-n-methyl-, (8alpha,9beta,10beta,12alpha)-
benzoylstaurosporine
cgp 41251
cgp 41 251
cgp-41251
cgp-41251
cgp-41251
midostaurin
midostaurin
midostaurin
midostaurin
midostaurin
midostaurin
midostaurin
midostaurin
midostaurin
n-((9s,10r,11r,13r)-10-methoxy-9-methyl-1-oxo-2,3,10,11,12,13-hexahydro-9,13-epoxy-1h,9h-diindolo(1,2,3-gh:3',2',1'-lm)pyrrolo(3,4-j)(1,7)benzodiazonin-11-yl)-n-methylbenzamide
nvp-pkc412
nvp-pkc412
pkc412
pkc 412
pkc-412
pkc-412
pkc-412
rydapt
rydapt

Clinical trials

NCT ID	Phase	Start date	Sponsor(s)
NCT06313437	Phase 1	Sep 30, 2024	Harvard University, Syndax Pharmaceuticals
NCT04982354	Phase 1/Phase 2 (Phase 2)	Dec 15, 2021	Baptist Health, Jazz Pharmaceuticals
NCT04496999	Phase 1	Nov 16, 2020	University of Bern
NCT04385290	Phase 1/Phase 2 (Phase 2)	Jun 30, 2020	Novartis, Pfizer, Technical University of Dresden
NCT04174612	Phase 3	Feb 1, 2020	Gruppo Italiano Malattie EMatologiche dell'Adulto
NCT04075747	Phase 1	Oct 31, 2019	Jazz Pharmaceuticals
NCT04027309	Phase 3	Sep 30, 2019	Astellas, Deutsch-Österreichische Studiengruppe Akute Myeloische Leukämie (AMLSG), Erasmus University Rotterdam, HOVON - Dutch Haemato-Oncology Association
NCT04097470	Phase 2	Sep 16, 2019	HOVON - Dutch Haemato-Oncology Association, Swiss Group for Clinical Cancer Research, University of Groningen
NCT03836209	Phase 2	Jul 31, 2019	Astellas, PrECOG, LLC., University of Pennsylvania
NCT03951961	Phase 2	Jul 1, 2019	Friedrich Schiller University, Ludwig Maximilians University, University of Jena
NCT03760445	Phase 1/Phase 2 (Phase 2)	May 31, 2019	Novartis
NCT03900949	Phase 1	Mar 21, 2019	OHSU Knight Cancer Institute, Oregon Health and Science University, Pfizer, University of Washington
NCT03591510	Phase 2	Oct 12, 2018	Novartis
NCT03207334	Phase 2	Sep 30, 2018	Novartis, University of Florida
NCT03258931	Phase 3	Aug 15, 2018	Arog Pharmaceuticals, Inc.
NCT03512197	Phase 3	Jul 20, 2018	Novartis
NCT03686345	Phase 2	Jul 1, 2018	University of Milan
NCT03280030	Phase 2	Apr 6, 2018	Novartis
NCT03379727	Phase 3	Feb 13, 2018	Novartis
NCT03092674	Phase 2/Phase 3 (Phase 3)	Dec 20, 2017	National Cancer Institute (NCI), Southwest Oncology Group

Showing 20 of 45 trials

Page 1 / 3

Organizations

Research & Development (40)

Organization	Org type	Trials	As lead sponsor	Phases	Earliest year
Novartis	For profit	25	15	4	2002
Harvard University	Academic/Hospital	5	3	3	2002
National Cancer Institute (NCI)	Government	5	2	2	2008
Stanford University	Academic/Hospital	3	3	1	2005
Astellas	For profit	2	0	2	2019
HOVON - Dutch Haemato-Oncology Association	Academic/Hospital	2	2	2	2019
Jazz Pharmaceuticals	For profit	2	1	2	2019
Pfizer	For profit	2	0	2	2019
Technical University of Dresden	Academic/Hospital	2	2	1	2012
University of Groningen	Academic/Hospital	2	1	1	2013
Arog Pharmaceuticals, Inc.	For profit	1	1	1	2018
Baptist Health	Academic/Hospital	1	1	1	2021
Case Western Reserve University	Academic/Hospital	1	1	1	2009
Celgene	For profit	1	0	1	2011
Cornell University	Academic/Hospital	1	0	1	2002
Deutsch-Österreichische Studiengruppe Akute Myeloische Leukämie (AMLSG)	Academic/Hospital	1	0	1	2019
Erasmus University Rotterdam	Academic/Hospital	1	0	1	2019
Friedrich Schiller University	Academic/Hospital	1	1	1	2019
Gruppo Italiano Malattie EMatologiche dell'Adulto	Academic/Hospital	1	1	1	2020
Ludwig Maximilians University	Academic/Hospital	1	0	1	2019

40 organizations

Page 1 / 2

Marketing (8)

Organization	Org type	Relationship	Date
Alvogen	For profit	MKTG	Aug 24, 2022
Dr. Reddy's Laboratories	For profit	MKTG	Jun 28, 2024
Lotus Pharmaceutical	For profit	MKTG	Aug 24, 2022
Lupin	For profit	MKTG	May 10, 2024
Novartis	For profit	NDA2	Apr 28, 2017
Novartis	For profit	MKTG	Apr 28, 2017
Novartis	For profit	NDA	Apr 28, 2017
Teva	For profit	MKTG	Apr 29, 2024