| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
ALK-IN-27 (NVL-655) targets ALK, a receptor tyrosine kinase involved in the pathogenesis of various cancers, including non-small cell lung cancer (NSCLC). It specifically inhibits ALK fusion proteins and activating mutations, including acquired resistance mutations such as the solvent front mutation G1202R and compound mutations G1202R/L1196M and G1202R/G1269A.
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| ln Vitro |
ALK-IN-27 shows antitumor activity. In Ba/F3 CLIP1-LTK cells, ALK-IN-27 has an IC50 of 2.7 nM. The inhibition of ALK leads to the disruption of ALK-mediated signaling and the inhibition of cell growth in ALK-dependent cancer cells.
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| Enzyme Assay |
A typical biochemical ALK kinase inhibition assay is performed using purified recombinant ALK kinase (wild-type or mutant variants). Increasing concentrations of ALK-IN-27 (0.01 nM to 1 uM) are pre-incubated with the enzyme and ATP. A peptide substrate is then added, and after a set reaction time, phosphorylation is measured using a time-resolved fluorescence resonance energy transfer (TR-FRET) or radiometric method to calculate the IC50 values for each mutation.
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| Cell Assay |
For cellular assays, Ba/F3 cells engineered to express CLIP1-LTK or other ALK fusion proteins are seeded in 96-well plates. Cells are treated with a dilution series of ALK-IN-27 for 72 hours. Cell viability is measured using a luminescence-based assay (CellTiter-Glo). For pharmacodynamic studies, cells are treated for 2-6 hours, and ALK autophosphorylation and downstream signaling (ERK, AKT) are measured by Western blot.
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| Animal Protocol |
No detailed in vivo animal experiment data is available for ALK-IN-27 in the provided references, though as an orally bioavailable, brain-penetrant ALK inhibitor, it is expected to show efficacy in mouse models of ALK-driven NSCLC and brain metastases.
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| ADME/Pharmacokinetics |
As an orally bioavailable compound with brain-penetrant properties, ALK-IN-27 (NVL-655) is designed to cross the blood-brain barrier, making it suitable for treating brain metastases in ALK-positive NSCLC. Specific PK parameters have not been detailed.
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| Toxicity/Toxicokinetics |
No specific toxicology data is reported for ALK-IN-27. As an ALK inhibitor targeting both native and resistant mutants, potential class-related toxicities may include gastrointestinal effects, fatigue, and edema, though selectivity may reduce off-target toxicity.
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| References | |
| Additional Infomation |
NVL-655, an ALK inhibitor, is an orally bioavailable, selective small-molecule receptor tyrosine kinase (RTK) anaplastic lymphoma kinase (ALK) inhibitor with blood-brain barrier penetration and potential antitumor activity. After oral administration, NVL-655 specifically targets, binds to, and inhibits ALK fusion proteins and activating mutations, including the acquired resistance mutation solvent front mutation (SFM) G1202R and the compound mutations G1202R/L1196M and G1202R/G1269A. Inhibition of ALK disrupts ALK-mediated signaling pathways and inhibits the growth of ALK-expressing tumor cells. ALK belongs to the insulin receptor superfamily and plays a crucial role in nervous system development. ALK is not expressed in healthy adult tissues, but ALK dysregulation and gene rearrangements are associated with various tumor cell types. NVL-655 can cross the blood-brain barrier (BBB), thus potentially exerting activity against EGFR-driven primary central nervous system (CNS) tumors and CNS metastases.
ALK-IN-27 (CAS: 2739866-40-9; compound 1) is a potent ALK inhibitor also known as NVL-655. It is an orally bioavailable, brain-penetrant, selective small molecule inhibitor of the receptor tyrosine kinase ALK (IC50 = 2.7 nM in Ba/F3 CLIP1-LTK cells). It inhibits ALK fusion proteins and activating mutations including G1202R, L1196M, and compound mutations. Molecular formula: C23H22ClFN6O; molecular weight: 452.91. |
| Molecular Formula |
C23H22CLFN6O
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|---|---|
| Molecular Weight |
452.911786556244
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| Exact Mass |
452.152
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| CAS # |
2739866-40-9
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| PubChem CID |
164718816
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| Appearance |
White to off-white solid powder
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
32
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| Complexity |
662
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCN1C2=C(CC3=CN(N=C3C4=C(C=C(C=C4)F)[C@H](OC5=C(N=CC2=C5)N)C)C)C(=N1)Cl
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| InChi Key |
FWZSCAQEBTVTOM-GFCCVEGCSA-N
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| InChi Code |
InChI=1S/C23H22ClFN6O/c1-4-31-21-13-8-19(23(26)27-10-13)32-12(2)17-9-15(25)5-6-16(17)20-14(11-30(3)28-20)7-18(21)22(24)29-31/h5-6,8-12H,4,7H2,1-3H3,(H2,26,27)/t12-/m1/s1
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| Chemical Name |
(19R)-5-chloro-3-ethyl-16-fluoro-10,19-dimethyl-20-oxa-3,4,10,11,23-pentazapentacyclo[19.3.1.02,6.08,12.013,18]pentacosa-1(25),2(6),4,8,11,13(18),14,16,21,23-decaen-22-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) |
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 | 2.2079 mL | 11.0397 mL | 22.0794 mL | |
| 5 mM | 0.4416 mL | 2.2079 mL | 4.4159 mL | |
| 10 mM | 0.2208 mL | 1.1040 mL | 2.2079 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/NCT06834074
Conditions:Non Small Cell Lung Cancer|ALK-positive Non-small Cell Lung Cancer (NSCLC)Link: https://clinicaltrials.gov/ct2/show/NCT06765109
Conditions:Non-small Cell Lung Cancer|Anaplastic Lymphoma Kinase-positiveLink: https://clinicaltrials.gov/ct2/show/NCT05384626
Conditions:Locally Advanced Solid Tumor|Metastatic Solid TumorProducts are for research use only; We do not sell to patients
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