BOS172722

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

Identification

Name
BOS172722
Accession Number
DB15498
Description

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
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Structure
Thumb
Weight
Average: 446.559
Monoisotopic: 446.254257618
Chemical Formula
C24H30N8O
Synonyms
Not Available
External IDs
  • BOS 172722
  • BOS-172722
  • BOS172722

Pharmacology

Indication
Not Available
Contraindications & Blackbox Warnings
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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
Affected organisms
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

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. [PubMed:30199249]
  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. [PubMed:31575759]
  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. [PubMed:23174302]
  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
1Active Not RecruitingTreatmentAdvanced 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
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
  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. [PubMed:30199249]
  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. [PubMed:31575759]

Drug created on October 06, 2019 09:37 / Updated on June 12, 2020 10:53

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