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DS1205 (DS-1205b) is a potent AXL kinase inhibitor with anti-lung cancer activity. It inhibits AXL with an IC50 of 1.3 nM. Also inhibits MER, MET, and TRKA, with IC50s of 63, 104, and 407 nM, respectively. DS-1205b monotherapy exerted significant antitumor activity in an NIH3T3-AXL allograft model. In an HCC827 xenograft model, combination treatment with DS-1205b and osimertinib significantly delayed on the onset of tumor resistance compared to osimertinib alone in a manner proportional to DS-1205b does. DS-1205b also showed a similar resistance delay effect with erlotinib combination in the same xenograft model.
| 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].
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| ln Vivo |
DS-1205b (3.1-50 mg/kg; orally given for 5 days) displays pAXL inhibition-mediated anti-tumor actions in mice [1].
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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. |
| 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. |
| References |
| 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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