NAV

BOS172722

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

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
3D
Similar Structures
Weight
Average: 446.559
Monoisotopic: 446.254257618
Chemical Formula
C24H30N8O
Synonyms
Not Available
External IDs
  • BOS 172722
  • BOS-172722
  • BOS172722
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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

TargetActionsOrganism
ADual specificity protein kinase TTK
inhibitor
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
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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
  1. 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]
  2. 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]
  3. 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]
  4. Cancer.gov Mps1 inhibitor BOS172722 definition [Link]
ChemSpider
61730800
BindingDB
241338
ChEMBL
CHEMBL3924132
PDBe Ligand
FMW
PDB Entries
6h3k

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAdvanced Nonhaematologic Malignancies1

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
PropertyValueSource
Water Solubility0.0112 mg/mLALOGPS
logP4.16ALOGPS
logP3.52Chemaxon
logS-4.6ALOGPS
pKa (Strongest Acidic)11.82Chemaxon
pKa (Strongest Basic)4.51Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count8Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area102.67 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity142.7 m3·mol-1Chemaxon
Polarizability50.91 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0000900000-e91d0462bd55405379e9
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-0000900000-3d474b4fcb44da0e413a
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-6001900000-5b486dfdc54674b4ff57
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-014j-0007900000-9f4b68d853a41f2d7d28
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-1009600000-bb5a55a6927b25c6ba4b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-01q9-0109300000-7fae9b242c40ffe4e8bd
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

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Details1. Dual specificity protein kinase TTK
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
  1. 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]
  2. 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