Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Tandutinib
- DrugBank Accession Number
- DB05465
- Background
MLN518 is a novel, oral, small molecule designed to inhibit type III receptor tyrosine kinases, including FLT3, (platelet-derived growth-factor receptor) PDGFR and c-KIT. Tyrosine kinases are enzymes involved in several cellular processes and are known to be activated in cancer cells to drive tumor growth. AML patients with FLT3 mutations experience earlier disease relapse and shorter survival rates compared to patients without these mutations. Approximately 25 to 30 percent of all adult AML patients have a mutation of the FLT3 gene. The use of MLN518 to treat AML has been granted fast-track status by the U.S. Food and Drug Administration. Phase I/II trials are underway.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Tandutinib (DB05465)
- Weight
- Average: 562.703
Monoisotopic: 562.326753862 - Chemical Formula
- C31H42N6O4
- Synonyms
- Tandutinib
- External IDs
- CT-53518
- CT53518
- MLN-518
Pharmacology
- Indication
Investigated for use/treatment in leukemia (myeloid).
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MLN518 is a novel quinazoline-based small molecule inhibitor of the FLT3, KIT, and platelet-derived growth-factor receptor (PDGFR) tyrosine kinases with that has been shown to have great efficacy in murine models of FLT3 ITD-positive leukemia. Experiments with mice demonstrate that at effective concentrations, MLN518 has mild toxicity toward normal hematopoiesis for FLT3 ITD-positive leukemia. MLN518 has also been shown to preferentially inhibit the growth of blast colonies from FLT3 ITD-positive as compared to ITD-negative patients with AML, without significantly affecting colony formation by normal human progenitor cells.
- Mechanism of action
MLN518 inhibits tyrosine kinases; Specifically, it is selective for FLT3, KIT, and platelet-derived growth-factor receptor (PDGFR).
Target Actions Organism AReceptor-type tyrosine-protein kinase FLT3 inhibitorHumans UPlatelet-derived growth factor D Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- 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
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- 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 softwareAcetaminophen The serum concentration of Acetaminophen can be increased when it is combined with Tandutinib. Acrivastine The risk or severity of QTc prolongation can be increased when Tandutinib is combined with Acrivastine. Adenosine The risk or severity of QTc prolongation can be increased when Tandutinib is combined with Adenosine. Ajmaline The risk or severity of QTc prolongation can be increased when Ajmaline is combined with Tandutinib. Albuterol The risk or severity of QTc prolongation can be increased when Salbutamol is combined with Tandutinib. - Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as n-arylpiperazines. These are organic compounds containing a piperazine ring where the nitrogen ring atom carries an aryl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazinanes
- Sub Class
- Piperazines
- Direct Parent
- N-arylpiperazines
- Alternative Parents
- Quinazolinamines / N-phenylureas / Piperazine carboxamides / Phenoxy compounds / Dialkylarylamines / Anisoles / Alkyl aryl ethers / Aminopyrimidines and derivatives / Piperidines / Imidolactams show 8 more
- Substituents
- Alkyl aryl ether / Amine / Aminopyrimidine / Anisole / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbonic acid derivative / Carbonyl group / Dialkylarylamine show 24 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- E1IO3ICJ9A
- CAS number
- 387867-13-2
- InChI Key
- UXXQOJXBIDBUAC-UHFFFAOYSA-N
- InChI
- InChI=1S/C31H42N6O4/c1-23(2)41-25-10-8-24(9-11-25)34-31(38)37-17-15-36(16-18-37)30-26-20-28(39-3)29(21-27(26)32-22-33-30)40-19-7-14-35-12-5-4-6-13-35/h8-11,20-23H,4-7,12-19H2,1-3H3,(H,34,38)
- IUPAC Name
- 4-{6-methoxy-7-[3-(piperidin-1-yl)propoxy]quinazolin-4-yl}-N-[4-(propan-2-yloxy)phenyl]piperazine-1-carboxamide
- SMILES
- COC1=C(OCCCN2CCCCC2)C=C2N=CN=C(N3CCN(CC3)C(=O)NC3=CC=C(OC(C)C)C=C3)C2=C1
References
- General References
- DeAngelo DJ, Stone RM, Heaney ML, Nimer SD, Paquette RL, Klisovic RB, Caligiuri MA, Cooper MR, Lecerf JM, Karol MD, Sheng S, Holford N, Curtin PT, Druker BJ, Heinrich MC: Phase 1 clinical results with tandutinib (MLN518), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome: safety, pharmacokinetics, and pharmacodynamics. Blood. 2006 Dec 1;108(12):3674-81. Epub 2006 Aug 10. [Article]
- Kiyoi H: [The present status of, and problems with the development of FLT3 kinase inhibitors]. Rinsho Ketsueki. 2006 Apr;47(4):270-7. [Article]
- Kiyoi H: [Possibility of targeting FLT3 kinase for the treatment of leukemia]. Rinsho Ketsueki. 2005 Mar;46(3):187-97. [Article]
- Griswold IJ, Shen LJ, La Rosee P, Demehri S, Heinrich MC, Braziel RM, McGreevey L, Haley AD, Giese N, Druker BJ, Deininger MW: Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis. Blood. 2004 Nov 1;104(9):2912-8. Epub 2004 Jul 8. [Article]
- Brownlow N, Vaid M, Dibb NJ: Tandutinib inhibits FMS receptor signalling, and macrophage and osteoclast formation in vitro. Leukemia. 2008 Jul;22(7):1452-3. doi: 10.1038/sj.leu.2405085. Epub 2008 Jan 10. [Article]
- External Links
- PubChem Compound
- 3038522
- PubChem Substance
- 175427013
- ChemSpider
- 2302085
- BindingDB
- 13535
- ChEBI
- 90237
- ChEMBL
- CHEMBL124660
- ZINC
- ZINC000003966243
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data2 Completed Treatment Anaplastic Astrocytoma (AA) / Anaplastic Oligodendroglioma (AO) / High Grade Glioma: Glioblastoma (GBM) / High Grade Glioma: Gliosarcoma / Mixed Anaplastic Oligoastrocytoma (AOA) 1 somestatus stop reason just information to hide 2 Completed Treatment Clear Cell Renal Cell Carcinoma / Recurrent Renal Cell Cancer / Stage IV Renal Cell Cancer 1 somestatus stop reason just information to hide 2 Completed Treatment Metastatic Cancer / Pain / Prostate Cancer 1 somestatus stop reason just information to hide 1 Completed Treatment Acute Myeloid Leukemia 1 somestatus stop reason just information to hide 1 Completed Treatment Acute Myeloid Leukemia / Myelodysplastic Syndrome 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0753 mg/mL ALOGPS logP 4.52 ALOGPS logP 4.34 Chemaxon logS -3.9 ALOGPS pKa (Strongest Acidic) 14.01 Chemaxon pKa (Strongest Basic) 9.03 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 92.29 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 162.58 m3·mol-1 Chemaxon Polarizability 64.1 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9955 Blood Brain Barrier + 0.9533 Caco-2 permeable + 0.5086 P-glycoprotein substrate Substrate 0.7822 P-glycoprotein inhibitor I Inhibitor 0.7745 P-glycoprotein inhibitor II Inhibitor 0.5673 Renal organic cation transporter Non-inhibitor 0.6446 CYP450 2C9 substrate Non-substrate 0.7887 CYP450 2D6 substrate Non-substrate 0.7857 CYP450 3A4 substrate Substrate 0.8103 CYP450 1A2 substrate Non-inhibitor 0.7872 CYP450 2C9 inhibitor Inhibitor 0.6167 CYP450 2D6 inhibitor Non-inhibitor 0.8805 CYP450 2C19 inhibitor Non-inhibitor 0.7293 CYP450 3A4 inhibitor Non-inhibitor 0.7285 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7373 Ames test Non AMES toxic 0.6764 Carcinogenicity Non-carcinogens 0.8818 Biodegradation Not ready biodegradable 0.996 Rat acute toxicity 2.2288 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.6936 hERG inhibition (predictor II) Inhibitor 0.8758
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 260.548776 predictedDarkChem Lite v0.1.0 [M-H]- 230.73833 predictedDeepCCS 1.0 (2019) [M+H]+ 261.588576 predictedDarkChem Lite v0.1.0 [M+H]+ 233.1339 predictedDeepCCS 1.0 (2019) [M+Na]+ 239.04642 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways
- Specific Function
- Atp binding
- Gene Name
- FLT3
- Uniprot ID
- P36888
- Uniprot Name
- Receptor-type tyrosine-protein kinase FLT3
- Molecular Weight
- 112902.51 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen for cells of mesenchymal origin. Plays an important role in wound healing. Induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis. Can initiate events that lead to a mesangial proliferative glomerulonephritis, including influx of monocytes and macrophages and production of extracellular matrix (By similarity)
- Specific Function
- Growth factor activity
- Gene Name
- PDGFD
- Uniprot ID
- Q9GZP0
- Uniprot Name
- Platelet-derived growth factor D
- Molecular Weight
- 42847.865 Da
Drug created at November 18, 2007 18:25 / Updated at August 26, 2024 19:22