BOS172722
Identification
- Generic Name
- BOS172722
- DrugBank Accession Number
- DB15498
- Background
BOS172722 is a novel and selective Monopolar spindle 1 (Mps1) kinase inhibitor identified as a potential anticancer agent.2 Normally, Mps1 supports the proper division of cancer cells, ensuring survival and replication. The key role of Mps1 in the growth of cancer cells renders it an appealing target for cancer treatment, as its inhibition could lead to favorable effects.1 An in vivo study combined BOS172722 with Paclitaxel for the treatment of triple hormone receptor negative breast cancer, and demonstrated promising synergistic effects.2
- Type
- Small Molecule
- Groups
- Experimental
- Structure
- Weight
- Average: 446.559
Monoisotopic: 446.254257618 - Chemical Formula
- C24H30N8O
- Synonyms
- Not Available
- External IDs
- BOS 172722
- BOS-172722
- BOS172722
Pharmacology
- Indication
Not Available
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- Pharmacodynamics
Not Available
- Mechanism of action
Mps1 is a protein kinase that is expressed in normal proliferating tissues and in certain actively dividing tumors. It acts during mitosis (cell division) and plays a crucial role in the alignment of chromosomes in cancer cells.1,4 Checkpoint activities by Mps1 normally inhibit the advancement of cancer cells from metaphase to anaphase until structural integrity and alignment occur. BOS172722 binds to Mps1, inhibiting its regulatory checkpoint activities.3 This inhibition causes accelerated cell division with increased missegregation errors that ultimately reduce the viability of malignant cells.1,4
Target Actions Organism ADual specificity protein kinase TTK inhibitorHumans - 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.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Not Available
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- Not Available
- CAS number
- 1578245-44-9
- InChI Key
- SGWLRDAOCLITOM-UHFFFAOYSA-N
- InChI
- InChI=1S/C24H30N8O/c1-7-33-19-11-16(22-31-27-14-32(22)6)8-9-18(19)29-23-25-12-17-10-15(2)28-21(20(17)30-23)26-13-24(3,4)5/h8-12,14H,7,13H2,1-6H3,(H,26,28)(H,25,29,30)
- IUPAC Name
- N8-(2,2-dimethylpropyl)-N2-[2-ethoxy-4-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl]-6-methylpyrido[3,4-d]pyrimidine-2,8-diamine
- SMILES
- CCOC1=CC(=CC=C1NC1=NC=C2C=C(C)N=C(NCC(C)(C)C)C2=N1)C1=NN=CN1C
References
- General References
- Woodward HL, Innocenti P, Cheung KJ, Hayes A, Roberts J, Henley AT, Faisal A, Mak GW, Box G, Westwood IM, Cronin N, Carter M, Valenti M, De Haven Brandon A, O'Fee L, Saville H, Schmitt J, Burke R, Broccatelli F, van Montfort RLM, Raynaud FI, Eccles SA, Linardopoulos S, Blagg J, Hoelder S: Introduction of a Methyl Group Curbs Metabolism of Pyrido[3,4- d]pyrimidine Monopolar Spindle 1 (MPS1) Inhibitors and Enables the Discovery of the Phase 1 Clinical Candidate N(2)-(2-Ethoxy-4-(4-methyl-4 H-1,2,4-triazol-3-yl)phenyl)-6-methyl- N(8)-neopentylpyrido[3,4- d]pyrimidine-2,8-diamine (BOS172722). J Med Chem. 2018 Sep 27;61(18):8226-8240. doi: 10.1021/acs.jmedchem.8b00690. Epub 2018 Sep 10. [Article]
- Anderhub SJ, Mak GW, Gurden MD, Faisal A, Drosopoulos K, Walsh K, Woodward HL, Innocenti P, Westwood IM, Naud S, Hayes A, Theofani E, Filosto S, Saville H, Burke R, van Montfort RLM, Raynaud FI, Blagg J, Hoelder S, Eccles SA, Linardopoulos S: High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers. Mol Cancer Ther. 2019 Oct;18(10):1696-1707. doi: 10.1158/1535-7163.MCT-18-1203. [Article]
- Lara-Gonzalez P, Westhorpe FG, Taylor SS: The spindle assembly checkpoint. Curr Biol. 2012 Nov 20;22(22):R966-80. doi: 10.1016/j.cub.2012.10.006. [Article]
- Cancer.gov Mps1 inhibitor BOS172722 definition [Link]
- External Links
- ChemSpider
- 61730800
- BindingDB
- 241338
- ChEMBL
- CHEMBL3924132
- PDBe Ligand
- FMW
- PDB Entries
- 6h3k
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 1 Completed Treatment Advanced Nonhaematologic Malignancies 1
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 0.0112 mg/mL ALOGPS logP 4.16 ALOGPS logP 3.52 Chemaxon logS -4.6 ALOGPS pKa (Strongest Acidic) 11.82 Chemaxon pKa (Strongest Basic) 4.51 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 102.67 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 142.7 m3·mol-1 Chemaxon Polarizability 50.91 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0000900000-e91d0462bd55405379e9 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0000900000-3d474b4fcb44da0e413a Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-6001900000-5b486dfdc54674b4ff57 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-014j-0007900000-9f4b68d853a41f2d7d28 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-1009600000-bb5a55a6927b25c6ba4b Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-01q9-0109300000-7fae9b242c40ffe4e8bd Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Protein tyrosine kinase activity
- Specific Function
- Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphoryla...
- Gene Name
- TTK
- Uniprot ID
- P33981
- Uniprot Name
- Dual specificity protein kinase TTK
- Molecular Weight
- 97071.5 Da
References
- Woodward HL, Innocenti P, Cheung KJ, Hayes A, Roberts J, Henley AT, Faisal A, Mak GW, Box G, Westwood IM, Cronin N, Carter M, Valenti M, De Haven Brandon A, O'Fee L, Saville H, Schmitt J, Burke R, Broccatelli F, van Montfort RLM, Raynaud FI, Eccles SA, Linardopoulos S, Blagg J, Hoelder S: Introduction of a Methyl Group Curbs Metabolism of Pyrido[3,4- d]pyrimidine Monopolar Spindle 1 (MPS1) Inhibitors and Enables the Discovery of the Phase 1 Clinical Candidate N(2)-(2-Ethoxy-4-(4-methyl-4 H-1,2,4-triazol-3-yl)phenyl)-6-methyl- N(8)-neopentylpyrido[3,4- d]pyrimidine-2,8-diamine (BOS172722). J Med Chem. 2018 Sep 27;61(18):8226-8240. doi: 10.1021/acs.jmedchem.8b00690. Epub 2018 Sep 10. [Article]
- Anderhub SJ, Mak GW, Gurden MD, Faisal A, Drosopoulos K, Walsh K, Woodward HL, Innocenti P, Westwood IM, Naud S, Hayes A, Theofani E, Filosto S, Saville H, Burke R, van Montfort RLM, Raynaud FI, Blagg J, Hoelder S, Eccles SA, Linardopoulos S: High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers. Mol Cancer Ther. 2019 Oct;18(10):1696-1707. doi: 10.1158/1535-7163.MCT-18-1203. [Article]
Drug created at October 06, 2019 15:37 / Updated at June 12, 2020 16:53