| Size | Price | Stock | Qty |
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| Targets |
FLT3 and FGFR[1]
FLT3 kinase and FGFR kinase. MAX-40279 is a dual inhibitor that targets wild-type and mutant FLT3 (including resistance mutations like FLT3D835Y) as well as FGFR, thereby disrupting multiple signaling pathways involved in cancer cell proliferation and survival. |
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| ln Vitro |
MAX-40279 is a dual and potent inhibitor of FLT3 and FGFR kinases. It is effective against FLT3 mutants such as FLT3 D835Y, suggesting it can overcome resistance to quizartinib and sorafenib. In vitro, it blocks FLT3 and FGFR phosphorylation and downstream signaling, leading to reduced cell proliferation.
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| ln Vivo |
In cell-based assays, MAX-40279 demonstrates potent anti-proliferative activity against FLT3-driven leukemia cell lines. It is described as having the potential for AML research, and its ability to inhibit FLT3 mutants suggests it could overcome clinical resistance. The hemiadipate and hemifumarate salt forms are developed for improved properties.
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| Enzyme Assay |
Cell-free FLT3 and FGFR kinase assays are performed using recombinant enzymes. The compound is incubated with the enzyme, a peptide substrate, and ATP for 30-60 minutes. Kinase activity is measured using a luminescence-based ADP detection kit. IC50 values are determined from dose-response curves (dual and potent inhibitor of FLT3 kinase and FGFR kinase).
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| Cell Assay |
FLT3-ITD-positive human leukemia cell lines (e.g., MV4-11) are seeded in 96-well plates and treated with increasing concentrations of MAX-40279 for 72 hours. Cell viability is measured using the MTT assay or CellTiter-Glo reagent. Apoptosis is measured by Annexin V/PI staining, and FLT3 phosphorylation is assessed by Western blot.
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| Animal Protocol |
For in vivo studies, MAX-40279 would be administered orally to mice bearing FLT3-ITD-driven tumor xenografts. Dosing is typically once or twice daily for 2-4 weeks. Tumor volumes are measured with calipers, and at study termination, tumors are excised for pharmacodynamic analysis, including FLT3 phosphorylation and downstream signaling.
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| ADME/Pharmacokinetics |
MAX-40279 is an orally active dual FLT3/FGFR kinase inhibitor. As the free base, it is formulated for in vivo studies. The hemiadipate salt form offers improved solubility and stability for research applications. The hemifumarate salt enhances bioavailability and stability, supporting favorable pharmacokinetics in preclinical studies.
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| Toxicity/Toxicokinetics |
No specific toxicity data are publicly available. As a dual FLT3/FGFR inhibitor, potential toxicities may include myelosuppression (due to FLT3 inhibition) and tissue-specific effects (due to FGFR inhibition). Comprehensive toxicological assessments have not been published. The compound is a research-grade chemical.
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| References | |
| Additional Infomation |
MAX-40279 is currently undergoing clinical trial NCT03412292 (MAX-40279 is for patients with acute myeloid leukemia (AML)). Nefiltinib is an orally bioavailable inhibitor of fibroblast growth factor receptor (FGFR) and FMS-like tyrosine kinase 3 (FLT3; CD135; STK1; FLK2) with potential antitumor activity. After oral administration, nefiltinib binds to and inhibits the activity of FGFR and FLT3 (including FLT3 mutants), thereby inhibiting the FGFR/FLT3-mediated signal transduction pathway. This inhibits the proliferation of FGFR/FLT3-overexpressing tumor cells. FGFRs are receptor tyrosine kinases upregulated in various tumor cell types. FLT3 is a class III receptor tyrosine kinase (RTK) overexpressed or mutated in most B-cell lineage tumors and AML. Both play crucial roles in cell proliferation and survival.
Other information: MAX-40279 is derived from patent WO2021180032. It is available as the free base (CAS 2070931-57-4), hemiadipate (CAS 2388506-44-1), and hemifumarate (CAS 2388506-43-0) salt forms. The hemifumarate salt has been studied in castration-resistant prostate cancer preclinical models. It is not an FDA-approved drug. |
| Molecular Formula |
C22H23FN6OS
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|---|---|
| Molecular Weight |
438.52
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| Exact Mass |
438.163
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| CAS # |
2070931-57-4
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| Related CAS # |
MAX-40279 hemifumarate;2388506-43-0;MAX-40279 hemiadipate;2388506-44-1;MAX-40279 hydrochloride;2388506-51-0
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| PubChem CID |
126495573
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
598
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C12C=NC(=NC=1C(=C(S2)C)C1=C(OC)C=C(C=C1)F)NC1=CN(N=C1)C1CCNCC1
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| InChi Key |
AVIOBQFPAGEICQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H23FN6OS/c1-13-20(17-4-3-14(23)9-18(17)30-2)21-19(31-13)11-25-22(28-21)27-15-10-26-29(12-15)16-5-7-24-8-6-16/h3-4,9-12,16,24H,5-8H2,1-2H3,(H,25,27,28)
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| Chemical Name |
7-(4-fluoro-2-methoxyphenyl)-6-methyl-N-(1-piperidin-4-ylpyrazol-4-yl)thieno[3,2-d]pyrimidin-2-amine
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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) |
DMSO: ≥ 25 mg/mL (57.01 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.70 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2804 mL | 11.4020 mL | 22.8040 mL | |
| 5 mM | 0.4561 mL | 2.2804 mL | 4.5608 mL | |
| 10 mM | 0.2280 mL | 1.1402 mL | 2.2804 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.
Link: https://clinicaltrials.gov/ct2/show/NCT05395780
Conditions:Gastric Cancer|Gastroesophageal Junction CancerLink: https://clinicaltrials.gov/ct2/show/NCT04183764
Conditions:Solid TumorLink: https://clinicaltrials.gov/ct2/show/NCT04187495
Conditions:AML
Title:MAX-40279 in Subjects With Acute Myelogenous Leukemia (AML)
Status:Unknown status
updateDate:2022-01-19
Ctid:NCT03412292
Link: https://clinicaltrials.gov/ct2/show/NCT03412292
Conditions:Acute Myelogenous Leukemia (AML)Link: https://clinicaltrials.gov/ct2/show/NCT05130021
Conditions:Metastatic Colorectal CancerLink: https://clinicaltrials.gov/ct2/show/NCT05061147
Conditions:Leukemia|Acute Myeloid Leukemia|Relapsed/Refractory Acute Myeloid Leukemia|Myelodysplastic SyndromeProducts are for research use only; We do not sell to patients
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