Midostaurin
Identification
- Summary
Midostaurin is an antineoplastic agent used to treat high-risk acute myeloid leukemia (AML) with specific mutations, aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematologic neoplasm (SM-AHN), or mast cell leukemia (MCL).
- Brand Names
- Rydapt
- Generic Name
- Midostaurin
- DrugBank Accession Number
- DB06595
- Background
Midostaurin (as Rydapt) is a multitarget kinase inhibitor for the treatment for adult patients with newly diagnosed acute myeloid leukemia (AML) who have a specific genetic mutation called FLT3. It was initially characterized as a potential broad-spectrum antineoplastic agent, with activity toward diverse solid and hematopoietic tumors 4. It was approved on April 28, 2017 and has shown to increase the overall survival rate in patients with AML as an adjunct therapy along with chemotherapeutic agents.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 570.649
Monoisotopic: 570.226705462 - Chemical Formula
- C35H30N4O4
- Synonyms
- 4'-N-benzoylstaurosporine
- Midostaurin
- External IDs
- CGP 41251
- CGP-41251
- NVP-PKC412
- PKC 412
- PKC-412
Pharmacology
- Indication
Investigated for use/treatment in adult patients with high-risk acute myeloid leukemia (AML) who are FLT3 mutation-positive, agressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Acute myeloid leukemia Regimen in combination with: Daunorubicin (DB00694), Cytarabine (DB00987) •••••••••••• Treatment of Aggressive systemic mastocytosis •••••••••••• Treatment of Mast cell leukemia •••••••••••• Treatment of Systemic mastocytosis •••••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
It targets multiple WT and mutated kinases that, when activated, constitutively stimulate aberrant signalling cascades that lead to malignancies such as AML and ASM. Alternative pharmacodynamic effect of midostaurin in prolonging QTc intervals was not clinically significant in patients with advanced SM or AML when compared to placebo. Midostaurin is therapeutically beneficial as a combination therapy for patients undergoing chemotherapy.
- Mechanism of action
It potently inhibits multiple receptor tyrosine kinases. Midostaurin and its major active metabolites CGP62221 and CGP52421 inhibit the activity of protein kinase C alpha (PKCalpha), VEGFR2, KIT, PDGFR and WT and/or mutant FLT3 tyrosine kinases. Inhibition of FLT3 receptor signalling cascades induces apoptosis of target leukemia cells expressing target receptors and mast cells, in addition to its antiproliferative activity toward multiple cancer cell lines 4. Midostaurin also interacts with organic anion transporter (OATP) 1A1 and multidrug resistance protein (MRP)-2 according to preliminary in vitro studies.
Target Actions Organism AProtein kinase C alpha type antagonistinhibitorHumans AVascular endothelial growth factor receptor 2 antagonistinhibitorHumans APlatelet-derived growth factor receptor alpha antagonistinhibitorHumans APlatelet-derived growth factor receptor beta antagonistinhibitorHumans AReceptor-type tyrosine-protein kinase FLT3 antagonistinhibitorHumans UMast/stem cell growth factor receptor Kit antagonistinhibitorHumans - Absorption
The time to reach maximum concentration ranges from 1-3 hrs in fasting patients. The maximum concentration and the time it takes to reach this concentration is reduced up to 20% in presence of a standard meal.
- Volume of distribution
The Vd of midostaurin is 95.2L. The parent drug and its main metabolites (CGP62221, CGP52421) are distributed in plasma in vitro.
- Protein binding
Midostaurin predominantly binds to α1-acid glycoprotein in vitro. The parent drug and its metabolites are >99.8% bound to plasma proteins in vitro.
- Metabolism
Midostaurin is primarily metabolized into CGP62221 and CGP52421 via hepatic CYP3A4 enzymatic activity. The metabolism of CGP62221 takes place initially in a linear relationship whereas CGP52421 formation is an inducible process 5.
Hover over products below to view reaction partners
- Route of elimination
Accounting for 95% of recovered dose eliminated through fecal excretion, 91% was determined as metabolites and 4% as unchanged parent drug. Remaining 5% of the recovered dose is eliminated via renal excretion.
- Half-life
Elimination half life is approximately 21 hrs for midostaurin, 32 hrs for CGP62221 and 482 hrs for CGP52421.
- Clearance
The clearance values of during the initial formation of metabolites are 1.47 L/h for CGP62221 metabolite and 0.501 L/h for CGP52421. 28 days following the oral administration of midostaurin, the clearance of CGP52421 may increase up to 5.2 fold in a recommended dose of 25 mg, resulting in a 2.1- to 2.5-fold increase in total clearance of midostaurin 5.
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
In a fertility study involving female and male rats, there is evidence of reproductive toxicity including reduced sperm count and decline pregnancy rates when administering 0.01 to 0.1 times the recommended dose in humans. LD50 for oral midostaurin for mouse, rat and rabbit are 300mg/kg, 980mg/kg and 3200mg/kg, respectively 8. Incidences of pulmonary toxicities including interstitial lung disease and pneumonitis have occured in few patients undergoing midostaurin monotherapy or combination therapy.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The metabolism of 1,2-Benzodiazepine can be decreased when combined with Midostaurin. Abametapir The serum concentration of Midostaurin can be increased when it is combined with Abametapir. Abatacept The metabolism of Midostaurin can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Midostaurin. Abiraterone The metabolism of Abiraterone can be increased when combined with Midostaurin. - Food Interactions
- Avoid St. John's Wort. This herb induces the CYP3A4 metabolism of midostaurin and may reduce its serum concentration.
- Exercise caution with grapefruit products. Grapefruit inhibits the CYP3A4 metabolism of midostaurin, which may increase its serum concentration.
- Take with food. Taking midostaurin with food increases the AUC, but it also prolongs the Tmax and reduces Cmax.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Rydapt Capsule, liquid filled 25 mg/1 Oral Novartis Pharmaceuticals Corporation 2017-04-28 Not applicable US Rydapt Capsule 25 mg Oral Novartis Europharm Limited 2020-12-16 Not applicable EU Rydapt Capsule 25 mg Oral Novartis Europharm Limited 2020-12-16 Not applicable EU Rydapt Capsule 25 mg Oral Novartis 2017-09-08 Not applicable Canada
Categories
- ATC Codes
- L01EX10 — Midostaurin
- Drug Categories
- Alkaloids
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Carbazoles
- Cytochrome P-450 CYP1A2 Inducers
- Cytochrome P-450 CYP1A2 Inducers (strength unknown)
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strong)
- Cytochrome P-450 CYP2B6 Inducers
- Cytochrome P-450 CYP2B6 Inducers (strength unknown)
- Cytochrome P-450 CYP2C19 Inducers
- Cytochrome P-450 CYP2C19 Inducers (strength unknown)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (weak)
- Cytochrome P-450 CYP2C8 Inducers
- Cytochrome P-450 CYP2C8 Inducers (strength unknown)
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Inducers
- Cytochrome P-450 CYP2C9 Inducers (strength unknown)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strong)
- Cytochrome P-450 CYP2E1 Inhibitors
- Cytochrome P-450 CYP2E1 Inhibitors (strong)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inducers (strong)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Inducers (strong)
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strong)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A5 Inducers
- Cytochrome P-450 CYP3A5 Inducers (strength unknown)
- Cytochrome P-450 CYP3A7 Inducers
- Cytochrome P-450 CYP3A7 Inducers (strength unknown)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Indole Alkaloids
- Indoles
- Indolizidines
- Indolizines
- Kinase Inhibitor
- Narrow Therapeutic Index Drugs
- Protein Kinase C, antagonists & inhibitors
- Protein Kinase Inhibitors
- Receptor Tyrosine Kinase Inhibitors
- Tyrosine Kinase Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as indolocarbazoles. These are polycyclic aromatic compounds containing an indole fused to a carbazole.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- Carbazoles
- Direct Parent
- Indolocarbazoles
- Alternative Parents
- Pyrrolo[2,3-a]carbazoles / Pyrroloindoles / Isoindolones / Benzamides / Indoles / Benzoyl derivatives / Oxanes / Tertiary carboxylic acid amides / Heteroaromatic compounds / Pyrroles show 9 more
- Substituents
- Aromatic heteropolycyclic compound / Azacycle / Benzamide / Benzenoid / Benzoic acid or derivatives / Benzoyl / Carboxamide group / Carboxylic acid derivative / Dialkyl ether / Ether show 22 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- benzamides, gamma-lactam, organic heterooctacyclic compound, indolocarbazole (CHEBI:63452)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- ID912S5VON
- CAS number
- 120685-11-2
- InChI Key
- BMGQWWVMWDBQGC-IIFHNQTCSA-N
- InChI
- InChI=1S/C35H30N4O4/c1-35-32(42-3)25(37(2)34(41)19-11-5-4-6-12-19)17-26(43-35)38-23-15-9-7-13-20(23)28-29-22(18-36-33(29)40)27-21-14-8-10-16-24(21)39(35)31(27)30(28)38/h4-16,25-26,32H,17-18H2,1-3H3,(H,36,40)/t25-,26-,32-,35+/m1/s1
- IUPAC Name
- N-[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.1^{2,6}.0^{7,28}.0^{8,13}.0^{15,19}.0^{20,27}.0^{21,26}]nonacosa-8(13),9,11,14(28),15(19),20(27),21(26),22,24-nonaen-4-yl]-N-methylbenzamide
- SMILES
- CO[C@@H]1[C@@H](C[C@H]2O[C@]1(C)N1C3=C(C=CC=C3)C3=C1C1=C(C4=C(C=CC=C4)N21)C1=C3CNC1=O)N(C)C(=O)C1=CC=CC=C1
References
- General References
- Fischer T, Stone RM, Deangelo DJ, Galinsky I, Estey E, Lanza C, Fox E, Ehninger G, Feldman EJ, Schiller GJ, Klimek VM, Nimer SD, Gilliland DG, Dutreix C, Huntsman-Labed A, Virkus J, Giles FJ: Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010 Oct 1;28(28):4339-45. doi: 10.1200/JCO.2010.28.9678. Epub 2010 Aug 23. [Article]
- Millward MJ, House C, Bowtell D, Webster L, Olver IN, Gore M, Copeman M, Lynch K, Yap A, Wang Y, Cohen PS, Zalcberg J: The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study. Br J Cancer. 2006 Oct 9;95(7):829-34. Epub 2006 Sep 12. [Article]
- Gotlib J, Kluin-Nelemans HC, George TI, Akin C, Sotlar K, Hermine O, Awan FT, Hexner E, Mauro MJ, Sternberg DW, Villeneuve M, Huntsman Labed A, Stanek EJ, Hartmann K, Horny HP, Valent P, Reiter A: Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2530-41. doi: 10.1056/NEJMoa1513098. [Article]
- Gallogly MM, Lazarus HM: Midostaurin: an emerging treatment for acute myeloid leukemia patients. J Blood Med. 2016 Apr 19;7:73-83. doi: 10.2147/JBM.S100283. eCollection 2016. [Article]
- Yin OQ, Wang Y, Schran H: A mechanism-based population pharmacokinetic model for characterizing time-dependent pharmacokinetics of midostaurin and its metabolites in human subjects. Clin Pharmacokinet. 2008;47(12):807-16. doi: 10.2165/0003088-200847120-00005. [Article]
- Abmole Midostaurin MSDS [Link]
- Alfa Aesar Midostaurin MSDS [Link]
- Cayman Midostaurin MSDS [Link]
- FDA Approved Drug Products: RYDAPT (midostaurin) capsules [Link]
- External Links
- KEGG Drug
- D05029
- PubChem Compound
- 9829523
- PubChem Substance
- 347827778
- ChemSpider
- 8005258
- BindingDB
- 50326053
- 1919083
- ChEBI
- 63452
- ChEMBL
- CHEMBL608533
- ZINC
- ZINC000100013130
- PDBe Ligand
- 2K2
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Midostaurin
- PDB Entries
- 4nct
- FDA label
- Download (306 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Acute Myeloid Leukemia / Myelodysplastic Syndrome With Excess Blasts-2 (MDS-EB-2) 1 3 Active Not Recruiting Treatment Leukemias 1 3 Completed Treatment Acute Myeloid Leukemia 2 3 Recruiting Treatment Acute Myeloid Leukemia With FMS-like Tyrosine Kinase (FLT3) / Internal Tandem Duplication (ITD) Mutation 1 3 Recruiting Treatment Newly Diagnosed FLT3 Mutated AML 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule, liquid filled Oral 25 mg/1 Capsule Oral 25 mg Capsule Oral Capsule, liquid filled Oral 25 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8575146 No 2013-11-05 2030-12-02 US US7973031 No 2011-07-05 2024-10-17 US US8222244 No 2012-07-17 2022-10-29 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 235-260 Alfa Aesar MSDS water solubility <1mg/mL Abmole MSDS logP 5.89 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0157 mg/mL ALOGPS logP 4.52 ALOGPS logP 5.43 Chemaxon logS -4.6 ALOGPS pKa (Strongest Acidic) 13.45 Chemaxon pKa (Strongest Basic) -0.83 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 77.73 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 162.61 m3·mol-1 Chemaxon Polarizability 60.58 Å3 Chemaxon Number of Rings 9 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 243.868 predictedDeepCCS 1.0 (2019) [M+H]+ 245.76341 predictedDeepCCS 1.0 (2019) [M+Na]+ 251.82526 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- General Function
- Zinc ion binding
- Specific Function
- Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differenti...
- Gene Name
- PRKCA
- Uniprot ID
- P17252
- Uniprot Name
- Protein kinase C alpha type
- Molecular Weight
- 76749.445 Da
References
- Millward MJ, House C, Bowtell D, Webster L, Olver IN, Gore M, Copeman M, Lynch K, Yap A, Wang Y, Cohen PS, Zalcberg J: The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study. Br J Cancer. 2006 Oct 9;95(7):829-34. Epub 2006 Sep 12. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- General Function
- Vascular endothelial growth factor-activated receptor activity
- Specific Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
- Gene Name
- KDR
- Uniprot ID
- P35968
- Uniprot Name
- Vascular endothelial growth factor receptor 2
- Molecular Weight
- 151525.555 Da
References
- Millward MJ, House C, Bowtell D, Webster L, Olver IN, Gore M, Copeman M, Lynch K, Yap A, Wang Y, Cohen PS, Zalcberg J: The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study. Br J Cancer. 2006 Oct 9;95(7):829-34. Epub 2006 Sep 12. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- General Function
- Vascular endothelial growth factor-activated receptor activity
- Specific Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chem...
- Gene Name
- PDGFRA
- Uniprot ID
- P16234
- Uniprot Name
- Platelet-derived growth factor receptor alpha
- Molecular Weight
- 122668.46 Da
References
- Millward MJ, House C, Bowtell D, Webster L, Olver IN, Gore M, Copeman M, Lynch K, Yap A, Wang Y, Cohen PS, Zalcberg J: The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study. Br J Cancer. 2006 Oct 9;95(7):829-34. Epub 2006 Sep 12. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- General Function
- Vascular endothelial growth factor binding
- Specific Function
- Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...
- Gene Name
- PDGFRB
- Uniprot ID
- P09619
- Uniprot Name
- Platelet-derived growth factor receptor beta
- Molecular Weight
- 123966.895 Da
References
- Millward MJ, House C, Bowtell D, Webster L, Olver IN, Gore M, Copeman M, Lynch K, Yap A, Wang Y, Cohen PS, Zalcberg J: The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study. Br J Cancer. 2006 Oct 9;95(7):829-34. Epub 2006 Sep 12. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- General Function
- Vascular endothelial growth factor-activated receptor activity
- Specific Function
- Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells...
- Gene Name
- FLT3
- Uniprot ID
- P36888
- Uniprot Name
- Receptor-type tyrosine-protein kinase FLT3
- Molecular Weight
- 112902.51 Da
References
- Millward MJ, House C, Bowtell D, Webster L, Olver IN, Gore M, Copeman M, Lynch K, Yap A, Wang Y, Cohen PS, Zalcberg J: The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study. Br J Cancer. 2006 Oct 9;95(7):829-34. Epub 2006 Sep 12. [Article]
- Gallogly MM, Lazarus HM: Midostaurin: an emerging treatment for acute myeloid leukemia patients. J Blood Med. 2016 Apr 19;7:73-83. doi: 10.2147/JBM.S100283. eCollection 2016. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- AntagonistInhibitor
- General Function
- Transmembrane receptor protein tyrosine kinase activity
- Specific Function
- Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell main...
- Gene Name
- KIT
- Uniprot ID
- P10721
- Uniprot Name
- Mast/stem cell growth factor receptor Kit
- Molecular Weight
- 109863.655 Da
References
- Millward MJ, House C, Bowtell D, Webster L, Olver IN, Gore M, Copeman M, Lynch K, Yap A, Wang Y, Cohen PS, Zalcberg J: The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study. Br J Cancer. 2006 Oct 9;95(7):829-34. Epub 2006 Sep 12. [Article]
Enzymes
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Components:
Name | UniProt ID |
---|---|
Cytochrome P450 3A4 | P08684 |
Cytochrome P450 3A43 | Q9HB55 |
Cytochrome P450 3A5 | P20815 |
Cytochrome P450 3A7 | P24462 |
References
- He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [Article]
- FDA Approved Drug Products: RYDAPT (midostaurin) capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- InhibitorInducer
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [Article]
- FDA Approved Drug Products: RYDAPT (midostaurin) capsules [Link]
- Midostaurin fDA [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [Article]
- FDA Approved Drug Products: RYDAPT (midostaurin) capsules [Link]
- Midostaurin FDA Label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- InhibitorInducer
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [Article]
- Midostaurin EMA Label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- InhibitorInducer
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [Article]
- Midostaurin FDA label [File]
- Midostaurin EMA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- InhibitorInducer
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [Article]
- Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism and Excretion Studies of a BDDCS II Drug [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A7
- Uniprot ID
- P24462
- Uniprot Name
- Cytochrome P450 3A7
- Molecular Weight
- 57525.03 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Monooxygenase activity
- Specific Function
- Exhibits low testosterone 6-beta-hydroxylase activity.
- Gene Name
- CYP3A43
- Uniprot ID
- Q9HB55
- Uniprot Name
- Cytochrome P450 3A43
- Molecular Weight
- 57669.21 Da
Drug created at March 19, 2008 16:39 / Updated at February 20, 2024 23:54