| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
DS1205 targets AXL kinase, a member of the TAM (Tyro3, AXL, Mer) receptor tyrosine kinase family. It also inhibits MER, MET, and TRKA with lower potency. By inhibiting AXL signaling, DS1205 suppresses downstream pathways such as PI3K/AKT and MAPK, which are involved in cell migration, proliferation, and survival.
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| ln Vitro |
NIH3T3-AXL cells' hGAS6-induced migration is inhibited by DS-1205b (0.3-33 μM; 2-24 hours) (EC50=2.7 nM) [1]. In NIH3T3-AXL cells, DS-1205b (1-10000 μM; 2-24 hours) strongly reduces AXL phosphorylation. While DS-1205b decreases NIH3T3 cell proliferation, growth (GI50>10,000 nM) is not substantially inhibited[1].
In vitro, DS1205b inhibits hGAS6-induced migration of NIH3T3-AXL cells with an EC50 of 2.7 nM. It strongly reduces AXL phosphorylation in NIH3T3-AXL cells at concentrations above 10 nM. The compound does not substantially inhibit NIH3T3 cell proliferation (GI50 >10,000 nM). It slightly inhibits AKT phosphorylation in a dose-dependent manner. |
| ln Vivo |
DS-1205b (3.1-50 mg/kg; orally given for 5 days) displays pAXL inhibition-mediated anti-tumor actions in mice [1].
In vivo, DS1205b (3.1-50 mg/kg; oral, twice daily for 5 days) displays pAXL inhibition-mediated anti-tumor actions in mice. In an NIH3T3-AXL allograft model, it inhibits tumor growth by 39-94%. In an HCC827 xenograft model, combination treatment with DS1205b and osimertinib significantly delays the onset of tumor resistance compared to osimertinib alone. |
| Enzyme Assay |
The in vitro enzyme assay for DS1205b involves measuring the inhibition of AXL kinase activity. Recombinant AXL kinase is incubated with a substrate peptide and ATP in the presence of varying compound concentrations. The IC50 value is determined by quantifying the reduction in substrate phosphorylation using techniques such as radioactive or fluorescence-based assays.
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| Cell Assay |
Western Blot analysis [1]
Cell Types: NIH3T3-AXL cells Tested Concentrations: 1, 10, 100, 1000, 10000 μM Incubation Duration: 2, 24 hrs (hours) Experimental Results: The phosphorylation of AXL is completely inhibited when the concentration is higher than 10 nM. Slightly inhibits phosphorylation of AKT serine/threonine kinase in a dose-dependent manner. Cellular assays are performed using NIH3T3-AXL cells. Cells are treated with DS1205b (0.3-33 µM) for 2-24 hours. Cell migration is assessed using transwell assays, and AXL phosphorylation is measured by Western blot analysis. Cell proliferation is evaluated using standard growth assays. |
| Animal Protocol |
Animal/Disease Models: Female NOD/Shi-scid IL-2Rγ KO Jic mice implanted with NIH3T3-AXL tumor mass [1]
Doses: 3.1, 6.3, 13, 25, 50 mg/kg Route of Administration: Po, twice a day, Result lasted for 5 days: inhibited tumor growth by 39-94%. Reduces AXL and AKT phosphorylation in tumors. In vivo animal studies are conducted in female NOD/Shi-scid IL-2Rγ KO Jic mice implanted with NIH3T3-AXL tumor mass. DS1205b is administered orally at doses of 3.1, 6.3, 13, 25, and 50 mg/kg twice daily for 5 days. Tumor growth inhibition is measured, and AXL and AKT phosphorylation in tumors is assessed by Western blotting. |
| ADME/Pharmacokinetics |
DS1205b is an orally bioavailable compound. It is administered orally in animal studies, indicating favorable pharmacokinetic properties. The compound shows dose-proportional antitumor activity. Specific PK parameters such as half-life, Cmax, and AUC are not detailed in the available sources.
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| Toxicity/Toxicokinetics |
Toxicity data for DS1205b are not reported in the available sources. The compound has been evaluated in animal models at doses up to 50 mg/kg without obvious toxicity reported in the described studies. Specific toxicological profiles are not available.
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| References | |
| Additional Infomation |
DS1205b is being investigated as a potential therapeutic agent for lung cancer, particularly in combination with EGFR inhibitors to overcome resistance. It is a research compound and is not an approved therapeutic drug. The compound is available from chemical suppliers for research use only.
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| Molecular Formula |
C41H42FN5O7
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|---|---|
| Molecular Weight |
735.799893856049
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| Exact Mass |
735.306
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| CAS # |
1855860-24-0
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| Related CAS # |
1855860-24-0;1855861-49-2 (mesylate);1855861-62-9 (phosphate);1855861-63-0 (2 sulfate); 1855861-64-1 (1.5 sulfate); 2407835-63-4 (X sulfate);
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| PubChem CID |
129110632
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| Appearance |
Off-white to yellow solid powder
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
54
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| Complexity |
1330
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC1=C(C2C(N)=NC=C(C=2)C2C=CC(=C(C=2)OC)OC[C@H]2COCCO2)C=CC(=C1)NC(C1C(C(C2C=CC(C)=CN=2)=CN(C=1)CC1CCOCC1)=O)=O
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| InChi Key |
ZOEILZXFYPPMTR-SSEXGKCCSA-N
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| InChi Code |
InChI=1S/C41H42FN5O7/c1-25-3-7-36(44-18-25)33-21-47(20-26-9-11-51-12-10-26)22-34(39(33)48)41(49)46-29-5-6-31(35(42)17-29)32-15-28(19-45-40(32)43)27-4-8-37(38(16-27)50-2)54-24-30-23-52-13-14-53-30/h3-8,15-19,21-22,26,30H,9-14,20,23-24H2,1-2H3,(H2,43,45)(H,46,49)/t30-/m1/s1
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| Chemical Name |
(R)-N-(4-(5-(4-((1,4-dioxan-2-yl)methoxy)-3-methoxyphenyl)-2-aminopyridin-3-yl)-3-fluorophenyl)-5-methyl-4'-oxo-1'-((tetrahydro-2H-pyran-4-yl)methyl)-1',4'-dihydro-[2,3'-bipyridine]-5'-carboxamide
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| Synonyms |
DS-1205bDS-1205 DS 1205b DS1205bDS 1205 DS1205 DS-1206b
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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 : ~50 mg/mL (~67.95 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.40 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 | 1.3591 mL | 6.7953 mL | 13.5906 mL | |
| 5 mM | 0.2718 mL | 1.3591 mL | 2.7181 mL | |
| 10 mM | 0.1359 mL | 0.6795 mL | 1.3591 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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