BOS172722
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MedKoo CAT#: 206988

CAS#: 1578245-44-9

Description: BOS172722 is a potent and selective MPS1 inhibitor with IC50 = 11 nM. BOS172722 showed very good bioavailability in all three species despite very modest solubility at physiological pH. Monopolar spindle 1 (MPS1) occupies a central role in mitosis and is one of the main components of the spindle assembly checkpoint. The MPS1 kinase is an attractive cancer target.

Chemical Structure

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BOS172722
CAS# 1578245-44-9
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 206988
Name: BOS172722
CAS#: 1578245-44-9
Chemical Formula: C24H30N8O
Exact Mass: 446.25
Molecular Weight: 446.560
Elemental Analysis: C, 64.55; H, 6.77; N, 25.09; O, 3.58

Price and Availability

Size Price Availability Quantity
25mg USD 750 2 Weeks
50mg USD 1250 2 Weeks
100mg USD 2050 2 Weeks
200mg USD 2950 2 Weeks
500mg USD 3950 2 Weeks
1g USD 5950 2 Weeks
2g USD 9950 2 Weeks
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Synonym: BOS172722; BOS-172722; BOS 172722;

IUPAC/Chemical Name: N2-(2-ethoxy-4-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-6-methyl-N8-neopentylpyrido[3,4-d]pyrimidine-2,8-diamine

InChi Key: SGWLRDAOCLITOM-UHFFFAOYSA-N

InChi Code: 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)

SMILES Code: CC1=CC2=CN=C(NC3=CC=C(C4=NN=CN4C)C=C3OCC)N=C2C(NCC(C)(C)C)=N1

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >3 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Product Data
Instruction:
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Biological target: Inhibitor of monopolar spindle 1 (MPS1) checkpoint.
In vitro activity: Optimizing HLM stability proved challenging since it was not possible to identify a consistent site of metabolism and lowering lipophilicity proved unsuccessful. Key to overcoming this problem was the finding that introduction of a methyl group at the 6-position of the pyrido[3,4- d]pyrimidine core significantly improved HLM stability. Met ID studies suggested that the methyl group suppressed metabolism at the distant aniline portion of the molecule, likely by blocking the preferred pharmacophore through which P450 recognized the compound. This work ultimately led to the discovery of BOS172722 as a Phase 1 clinical candidate. Reference: 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 N2-(2-Ethoxy-4-(4-methyl-4 H-1,2,4-triazol-3-yl)phenyl)-6-methyl- N8-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. PMID: 30199249; PMCID: PMC6166229.
In vivo activity: In in vivo pharmacodynamic experiments, BOS172722 potently inhibits the spindle assembly checkpoint induced by paclitaxel in human tumor xenograft models of TNBC, as measured by inhibition of the phosphorylation of histone H3 and the phosphorylation of the MPS1 substrate, KNL1. This mechanistic synergy results in significant in vivo efficacy, with robust tumor regressions observed for the combination of BOS172722 and paclitaxel versus either agent alone in long-term efficacy studies in multiple human tumor xenograft TNBC models, including a patient-derived xenograft and a systemic metastasis model. The current target indication for BOS172722 is TNBC, based on their high sensitivity to MPS1 inhibition, the well-defined clinical patient population with high unmet need, and the synergy observed with paclitaxel. Reference: 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. PMID: 31575759.

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 5.0 11.19
1M HCl 65.0 145.56

Preparing Stock Solutions

The following data is based on the product molecular weight 446.56 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 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 N2-(2-Ethoxy-4-(4-methyl-4 H-1,2,4-triazol-3-yl)phenyl)-6-methyl- N8-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. PMID: 30199249; PMCID: PMC6166229.
In vitro protocol: 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 N2-(2-Ethoxy-4-(4-methyl-4 H-1,2,4-triazol-3-yl)phenyl)-6-methyl- N8-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. PMID: 30199249; PMCID: PMC6166229.
In vivo protocol: 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. PMID: 31575759.

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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 10. doi: 10.1021/acs.jmedchem.8b00690. [Epub ahead of print] PubMed PMID:
30199249.