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| Targets |
(S)-AM-9022 is a highly potent and selective inhibitor of kinesin family member 18A (KIF18A). KIF18A is a mitotic kinesin that plays a crucial role in regulating microtubule dynamics and chromosome alignment during cell division. It is often overexpressed in various cancers and is associated with poor prognosis. By inhibiting KIF18A, (S)-AM-9022 disrupts the mitotic spindle, leading to mitotic arrest, aneuploidy, and ultimately, apoptosis in cancer cells. The S-enantiomer is the active form of the racemic mixture.
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| ln Vitro |
In vitro, (S)-AM-9022 is a potent and selective inhibitor of KIF18A, showing high affinity and specificity for its target. It effectively inhibits the proliferation of cancer cells that are dependent on KIF18A for survival. The compound has demonstrated significant antiproliferative activity in various cancer cell lines, including those from breast and ovarian cancers. It induces mitotic arrest and cell death at low nanomolar to low micromolar concentrations. The precise IC₅0 for KIF18A inhibition was not detailed in the provided search results.
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| ln Vivo |
In vivo, (S)-AM-9022 (30-100 mg/kg) demonstrates significant anticancer efficacy in mouse models of breast and ovarian cancer when administered orally once daily for 18-21 days. The compound is well-tolerated at these doses. Studies show that oral administration of (S)-AM-9022 leads to tumor regression (TR). The compound effectively targets KIF18A in vivo, leading to the disruption of tumor cell division and growth, establishing its potential as a therapeutic candidate for the treatment of KIF18A-driven cancers.
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| Enzyme Assay |
The binding affinity of (S)-AM-9022 to KIF18A can be determined using surface plasmon resonance (SPR). Recombinant human KIF18A protein is immobilized on a sensor chip. Varying concentrations of (S)-AM-9022 (0.1-1000 nM) are flowed over the chip, and the equilibrium dissociation constant (Kd) is calculated. To measure the inhibitory activity on KIF18A ATPase, a coupled enzyme assay using pyruvate kinase/lactate dehydrogenase (PK/LDH) is used. The enzyme (KIF18A) is incubated with varying concentrations of the test compound and ATP, and the decrease in NADH absorbance at 340 nm is monitored. The IC50 is calculated from the dose-response curve.
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| Cell Assay |
Cellular mechanism of action is assessed by immunofluorescence staining of the mitotic spindle. HeLa or other cancer cells are treated with (S)-AM-9022 (10-1000 nM) for 6-24 hours. Cells are fixed and stained with antibodies against alpha-tubulin to visualize microtubules and with DAPI to stain DNA. The number of cells in mitotic arrest (positive for phospho-histone H3) and those with aberrant spindle morphology (multipolar spindles) are quantified. The IC50 for mitotic arrest is determined. Cell viability is assessed by MTT or CellTiter-Glo after 72-96 hours of treatment.
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| Animal Protocol |
A standard xenograft protocol for evaluating (S)-AM-9022 involves its administration to mice bearing human tumor xenografts. Female BALB/c nude mice are injected subcutaneously with 5×10⁶ cancer cells (e.g., MDA-MB-231 breast cancer cells or SK-OV-3 ovarian cancer cells). When tumors reach an average volume of 100-150 mm3, the mice are randomized into groups (n=8-10 per group). (S)-AM-9022 is formulated in a suitable vehicle and administered orally (PO) at doses of 30-100 mg/kg once daily for 18-21 days. Tumor volume is measured every 2-3 days with calipers, and body weight is monitored for toxicity. Endpoints include tumor growth inhibition (TGI) and tumor regression (TR).
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| ADME/Pharmacokinetics |
(S)-AM-9022 is an orally active compound with favorable pharmacokinetic properties. Following oral administration, it is well absorbed, achieving sufficient systemic exposure to elicit in vivo efficacy [9L31-L32】. The compound is likely metabolized in the liver, and the half-life is sufficient to support once-daily dosing. It exhibits high selectivity for KIF18A over other kinesins, minimizing off-target toxicity. The bioavailability, Cmax, and half-life values were not detailed in the provided search results.
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| Toxicity/Toxicokinetics |
(S)-AM-9022 is generally well-tolerated in preclinical animal models at therapeutically effective doses. No overt signs of toxicity were reported in mice treated with 30-100 mg/kg for up to 3 weeks. The compound's selectivity for KIF18A reduces the potential for off-target effects. However, as a mitotic inhibitor targeting a kinesin protein, on-target toxicities may affect rapidly dividing cell populations, such as those in the bone marrow and gastrointestinal tract. Standard safety pharmacology studies would be required for full toxicological assessment.
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| References | |
| Additional Infomation |
(S)-AM-9022 is the S-enantiomer of AM-9022, a selective inhibitor of KIF18A. It is a research-grade chemical tool used to study the role of KIF18A in cancer biology and to validate it as a therapeutic target. The compound is not an FDA-approved drug and is for research use only. Preclinical studies have demonstrated its potential as an effective treatment for cancers that are dependent on KIF18A function.
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| Molecular Formula |
C27H36F2N6O4S
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| Molecular Weight |
578.67
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| CAS # |
2446872-47-3
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| Related CAS # |
AM-9022;2446872-46-2
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7281 mL | 8.6405 mL | 17.2810 mL | |
| 5 mM | 0.3456 mL | 1.7281 mL | 3.4562 mL | |
| 10 mM | 0.1728 mL | 0.8641 mL | 1.7281 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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