BOS172722 targets monopolar spindle 1 (MPS1/TTK), a dual-specificity kinase that plays a central role in mitosis. MPS1 supports the proper division of cancer cells, ensuring survival and replication. By inhibiting MPS1, BOS172722 potentially results in increased tumor cell death and decreased tumor growth. The compound has a biochemical IC50 of 11 nM and displays 100-fold selectivity over CDK2. Its high selectivity for MPS1 over other kinases contributes to its potential as a targeted anticancer agent.

BOS-172722 has an IC50 of 2 nM and is a monopolar spindle 1 (MPS1) checkpoint equivalent. Additionally, BOS-172722 may be able to treat different types of breast cancer [1].
In vitro, BOS172722 inhibits MPS1 kinase activity with an IC50 of 2-11 nM. The compound's potent and selective inhibition of MPS1 leads to mitotic defects and cell death in cancer cells. Studies have demonstrated its anti-proliferative effects in various cancer cell lines, particularly in breast cancer models. The compound's 100-fold selectivity over CDK2 indicates a favorable selectivity profile that may reduce off-target effects. Its mechanism of action involves disruption of the spindle assembly checkpoint, leading to mitotic catastrophe.

Excellent pharmacokinetic activity of BOS-172722 has been observed in mice, adsorbents, and dogs [1]. At 6 and 24 hours, BOS-172722 (50 mg/kg) causes an increase in MPS1 autophosphorylation adsorption [1].
In vivo, BOS172722 has been evaluated in preclinical models and has entered Phase 1 clinical trials. The compound shows high bioavailability in all three species despite very modest solubility at physiological pH. It has been investigated for the treatment of breast cancer, ER-positive breast cancer, and advanced solid tumours. The compound's ability to inhibit tumor growth in vivo supports its potential as an anticancer therapeutic.

In cell-free biochemical assays, BOS172722 is evaluated for its inhibitory activity against MPS1/TTK kinase. Kinase activity assays measure the compound's ability to inhibit phosphorylation of MPS1 substrates. The compound's IC50 of 11 nM and selectivity over CDK2 (100-fold) are determined using panel screening against a range of kinases. These assays confirm the compound's potent and selective inhibition of MPS1.

Cellular assays for BOS172722 involve evaluating its anti-proliferative effects in cancer cell lines, particularly breast cancer cell lines. The compound's ability to induce mitotic defects, cell cycle arrest, and apoptosis is assessed. Studies have examined the compound's effects on MPS1 activity, spindle assembly checkpoint function, and downstream signaling pathways. The compound's selectivity for cancer cells over normal cells has also been evaluated.

Animal/Disease Models: dog [2]. 1].
Doses: 1 mg/kg (intravenous (iv) (iv)injection), 5 mg/kg (oral) (pharmacokinetic/PK/PK analysis).
Doses: IV and PO.
Experimental Results: T1/2 = 12 hrs (hrs (hours)), Cmaxpo = 7770 nmol/L, AUCpo = 147035 h*nmol/L.
Animal models for BOS172722 include xenograft models of breast cancer and other solid tumours. The compound is typically administered orally or via injection. Studies have examined the compound's effects on tumor growth, survival, and biomarkers of MPS1 inhibition. The compound's pharmacokinetic properties, including bioavailability, have been evaluated in preclinical species. Phase 1 clinical trials have been conducted in patients with breast cancer and advanced solid tumours.

Pharmacokinetic studies show that BOS172722 has high bioavailability in all three species despite very modest solubility at physiological pH. The compound has a molecular weight of 446.55 g/mol with a formula of C24H30N8O. The CAS number is 1578245-44-9. The compound is a synthetic organic compound developed as a lead inhibitor of TTK (Mps1). Standard pharmacokinetic studies in preclinical species have characterized its absorption, distribution, metabolism, and excretion.

Toxicity data for BOS172722 are typical of MPS1 inhibitors. As a kinase inhibitor, the compound may have effects on normal dividing cells. The compound's selectivity for MPS1 over CDK2 (100-fold) suggests a favorable safety profile. Phase 1 clinical trials have evaluated the compound's safety and tolerability in patients. Standard safety precautions for handling pharmaceutical research compounds apply.

[1]. ARYL SULFONOHYDRAZIDES. WO 2014037750 A1.

BOS172722 is a novel selective monopolar spindle 1 (Mps1) kinase inhibitor considered a potential anticancer drug. Normally, Mps1 supports the normal division of cancer cells, ensuring their survival and replication. The crucial role of Mps1 in cancer cell growth makes it a highly attractive target for cancer therapy, as inhibiting Mps1 may lead to beneficial therapeutic effects. An in vivo study combined BOS172722 with paclitaxel for the treatment of triple hormone receptor-negative breast cancer showed encouraging synergistic effects. The Mps1 inhibitor BOS172722 is an orally bioavailable selective serine/threonine protein kinase monopolar spindle 1 (Mps1; TTK) inhibitor with potential antitumor activity. After administration, the Mps1 inhibitor BOS172722 binds to and inhibits the activity of Mps1, a core component of the spindle assembly checkpoint (SAC). Inhibition of Mps1 activity impairs spindle assembly checkpoints, increases chromosome segregation errors, and reduces cancer cell survival. Mps1 is a bispecific protein kinase expressed in proliferating normal tissues and aberrantly overexpressed in certain tumor types. It is activated during mitosis and is essential for the normal function of spindle assembly checkpoints (SACs) and chromosome alignment. Mps1 is a protein kinase expressed in normal proliferating tissues and certain actively dividing tumors. It functions during mitosis (cell division) and plays a crucial role in chromosome alignment in cancer cells. Mps1 checkpoint activity typically inhibits cancer cell progression from metaphase to anaphase until chromosome structural integrity and alignment are complete. BOS172722 binds to Mps1, inhibiting its regulatory checkpoint activity. This inhibition leads to accelerated cell division and increased chromosome segregation errors, ultimately reducing the survival rate of malignant cells.
BOS172722 is a novel, potent and selective inhibitor of monopolar spindle 1 (MPS1/TTK) with an IC50 of 2-11 nM. It displays 100-fold selectivity over CDK2 and has been investigated for the treatment of breast cancer and advanced solid tumours. The compound has entered Phase 1 clinical trials. MPS1 supports the proper division of cancer cells, and its inhibition potentially results in increased tumor cell death. The CAS number is 1578245-44-9.

C24H30N8O

446.548003673553

446.25

C, 64.55; H, 6.77; N, 25.09; O, 3.58

1578245-44-9

73386890

Light yellow to yellow solid powder

4.3

2

8

8

33

616

0

SGWLRDAOCLITOM-UHFFFAOYSA-N

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)

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

BOS172722 BOS-172722 BOS 172722

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

1M HCl : 65 mg/mL (~145.56 mM)
DMSO : ~5 mg/mL (~11.20 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)