Midostaurin is a small molecule that inhibits multiple receptor tyrosine kinases. In vitro biochemical or cellular assays have shown that midostaurin or its major human active metabolites CGP62221 and CGP52421 inhibit the activity of wild type FLT3, FLT3 mutant kinases (ITD and TKD), KIT (wild type and D816V mutant), PDGFR-alfa/beta, VEGFR2, as well as members of the serine/threonine kinase PKC (protein kinase C) family. Midostaurin demonstrated the ability to inhibit FLT3 receptor signaling and cell proliferation, and it induced apoptosis in leukemic cells expressing ITD and TKD mutant FLT3 receptors or overexpressing wild type FLT3 and PDGF receptors. Midostaurin also demonstrated the ability to inhibit KIT signaling, cell proliferation and histamine release and induce apoptosis in mast cells.
Molecular weight: 570.65
Formula: C35H30N4O4
CLOGP: 5.49
LIPINSKI: 2
HAC: 8
HDO: 1
TPSA: 77.73
ALOGS: -4.56
ROTB: 3
Status: ONP
Legend: OFP - off patent OFM - off market ONP - on patent
Drug dosage:
None
ADMET properties:
None
Approvals:
Date
Agency
Company
Orphan
Sept. 18, 2017
EMA
Novartis Europharm Ltd
April 28, 2017
FDA
NOVARTIS PHARMS CORP
FDA Adverse Event Reporting System (Female)
MedDRA adverse event term
Likelihood ratio
Likelihood ratio threshold
Patients taking drug having adverse event
Patients taking drug not having adverse event
Patients not taking drug having adverse event
Patients not taking drug not having adverse event
Acute myeloid leukaemia recurrent
116.77
35.40
22
1332
1374
46683334
Minimal residual disease
58.49
35.40
8
1346
60
46684648
Febrile neutropenia
54.68
35.40
34
1320
94593
46590115
Abdominal wall wound
50.89
35.40
7
1347
55
46684653
Neutropenic colitis
50.79
35.40
12
1342
2220
46682488
Sepsis
47.93
35.40
36
1318
135978
46548730
Thrombocytopenia
45.69
35.40
34
1320
126547
46558161
Myeloblast percentage decreased
44.35
35.40
6
1348
41
46684667
Systemic mastocytosis
44.13
35.40
7
1347
156
46684552
Electrocardiogram QT prolonged
36.21
35.40
21
1333
51304
46633404
FDA Adverse Event Reporting System (Male)
MedDRA adverse event term
Likelihood ratio
Likelihood ratio threshold
Patients taking drug having adverse event
Patients taking drug not having adverse event
Patients not taking drug having adverse event
Patients not taking drug not having adverse event
Acute myeloid leukaemia recurrent
112.66
37.94
23
1210
1529
29949716
Tryptase increased
66.89
37.94
11
1222
215
29951030
Neutropenic colitis
56.55
37.94
14
1219
2216
29949029
Systemic mastocytosis
43.05
37.94
7
1226
127
29951118
Pharmacologic Action:
Source
Code
Description
ATC
L01EX10
ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS Other protein kinase inhibitors
Acid dissociation constants calculated using MoKa v3.0.0
Dissociation level
Dissociation constant
Type (acidic/basic)
pKa1
9.7
acidic
Orange Book patent data (new drug applications)
None
Orange Book exclusivity data (new drug applications)
Formulation strength
Trade name
Applicant
Application number
Approval date
Type
Dose form
Route
Exclusivity date
Description
25MG
RYDAPT
NOVARTIS
N207997
April 28, 2017
RX
CAPSULE
ORAL
April 28, 2022
NEW CHEMICAL ENTITY
25MG
RYDAPT
NOVARTIS
N207997
April 28, 2017
RX
CAPSULE
ORAL
April 28, 2024
TREATMENT OF ADULT PATIENTS WITH AGGRESSIVE SYSTEMIC MASTOCYTOSIS (ASM), SYSTEMIC MASTOCYTOSIS WITH ASSOCIATED HEMATOLOGICAL NEOPLASM (SM-AHN), OR MAST CELL LEUKEMIA (MCL)
25MG
RYDAPT
NOVARTIS
N207997
April 28, 2017
RX
CAPSULE
ORAL
April 28, 2024
TREATMENT OF ADULT PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA (AML) THAT IS FLT3 MUTATION-POSITIVE AS DETECTED BY AN FDA APPROVED TEST, IN COMBINULLTION WITH STANDARD CYTARABINE AND DAUNORUBICIN INDUCTION AND CYTARABINE CONSOLIDATION