| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Targets |
ALK and ROS1[1]
Iruplinalkib targets ALK and ROS1 tyrosine kinases, effectively inhibiting tyrosine autophosphorylation of ALK, mutant ALK, and EGFR, with IC50 values ranging from 5.38 to 16.74 nM. It is also a suppressive agent of the transporters MATE1, MATE2K, P-gp, and BCRP. |
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| ln Vitro |
Iruplinalkib (1.23-100 nM; 2 h) inhibits the growth of NCI-H3122 cells by blocking the phosphorylation of ALK and downstream RAS/MAPK/ERK and PI3K/Akt pathways. It also inhibits ROS1 phosphorylation in NIH-3T3 (CD74-ROS1) and Ba/F3 (SLC34A2-ROS1) cells at concentrations of 10-1000 nM.
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| ln Vivo |
Iruplinalkib (2.5-10 mg/kg; oral administration; 3 weeks) exhibits significant antitumor effects in mouse models of non-small cell lung cancer (NSCLC), demonstrating dose-dependent tumor growth inhibition without significant toxicity. It overcomes crizotinib-resistant mutations.
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| Enzyme Assay |
A typical ALK and ROS1 biochemical kinase assay is performed using recombinant ALK wild-type, mutant ALK (e.g., L1196M), and ROS1 kinases. Increasing concentrations of Iruplinalkib are incubated with each enzyme and ATP. Phosphorylation of a substrate peptide is measured using a homogeneous time-resolved fluorescence (HTRF) or radiometric method to determine IC50 values (5.38-16.74 nM).
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| Cell Assay |
For cellular assays, NCI-H3122 (EML4-ALK fusion) cells are seeded in 6-well plates. Cells are treated with Iruplinalkib (1.23, 3.7, 11.1, 33.3, 100 nM) for 2 hours, then lysed. Western blot analysis is performed using antibodies against p-ALK, total ALK, p-AKT, p-ERK, and loading controls to assess pathway inhibition. For ROS1 inhibition, NIH-3T3 (CD74-ROS1) and Ba/F3 (SLC34A2-ROS1) cells are similarly treated and analyzed.
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| Animal Protocol |
Iruplinalkib is evaluated in a mouse model of non-small cell lung cancer (NSCLC). Immunodeficient mice bearing established tumor xenografts (e.g., NCI-H3122) are randomized and treated with Iruplinalkib via oral administration at doses of 2.5, 5, or 10 mg/kg daily for 3 weeks. Tumor volumes are measured with calipers twice weekly. Tumor growth inhibition (TGI) is calculated, and tumors are collected at endpoint for immunohistochemical analysis of p-ALK and Ki67.
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| ADME/Pharmacokinetics |
As an orally active compound, Iruplinalkib is designed to have favorable oral bioavailability. Detailed PK parameters such as Cmax, Tmax, half-life, and AUC have not been specified in the provided references.
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| Toxicity/Toxicokinetics |
No specific toxicology data is detailed in the provided references, though Iruplinalkib shows good safety and promising anti-tumor activity in advanced NSCLC patients. Weight monitoring in animal studies indicates minimal toxicity at therapeutic doses.
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| References | |
| Additional Infomation |
Iruplinalkib is an orally administered small-molecule receptor tyrosine kinase (RTK) anaplastic lymphoma kinase (ALK) inhibitor with potential antitumor activity. After oral administration, Iruplinalkib binds to and inhibits the activity of ALK tyrosine kinase, ALK fusion protein, ALK point mutants (ALK L1196M, ALK C1156Y), and EGFR L858R/T790M. Inhibition of ALK blocks ALK-mediated signaling pathways and suppresses the growth of ALK-expressing tumor cells. ALK belongs to the insulin receptor superfamily and plays an important role in the development of the nervous system. ALK is not expressed in healthy adult tissues, but aberrant ALK expression and gene rearrangements are associated with various tumors. Furthermore, ALK mutations are associated with acquired resistance to small-molecule tyrosine kinase inhibitors.
Iruplinalkib (WX-0593; CAS: 1854943-32-0) is an orally active, selective ALK/ROS1 inhibitor with IC50 values of 5.38-16.74 nM. It effectively inhibits ALK autophosphorylation and overcomes crizotinib-resistant mutations. It exhibits antitumor activity in NSCLC mouse models and is being studied for advanced NSCLC with ALK or ROS1 rearrangements. Molecular formula: C29H38ClN6O2P; molecular weight: 569.08. |
| Molecular Formula |
C29H38CLN6O2P
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|---|---|
| Molecular Weight |
569.077785968781
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| Exact Mass |
568.248
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| CAS # |
1854943-32-0
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| PubChem CID |
118639856
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
5.4
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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 |
7
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| Heavy Atom Count |
39
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| Complexity |
829
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=NC(=NC=1NC1C=CC=CC=1P(C)(C)=O)NC1C=CC(=CC=1OC)N1CCC2(CCN(C)CC2)CC1
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| InChi Key |
ZPCCNHQDFZCULN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H38ClN6O2P/c1-35-15-11-29(12-16-35)13-17-36(18-14-29)21-9-10-23(25(19-21)38-2)33-28-31-20-22(30)27(34-28)32-24-7-5-6-8-26(24)39(3,4)37/h5-10,19-20H,11-18H2,1-4H3,(H2,31,32,33,34)
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| Chemical Name |
5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-[2-methoxy-4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)phenyl]pyrimidine-2,4-diamine
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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: 10 mg/mL (17.57 mM)
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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 | 1.7572 mL | 8.7861 mL | 17.5722 mL | |
| 5 mM | 0.3514 mL | 1.7572 mL | 3.5144 mL | |
| 10 mM | 0.1757 mL | 0.8786 mL | 1.7572 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/NCT07374614
Conditions:Non-Small Cell Lung Cancer|ALK|Iruplinalkib|Lorlatinib|Real-world Study|Observational StudyLink: https://clinicaltrials.gov/ct2/show/NCT07330076
Conditions:NSCLCLink: https://clinicaltrials.gov/ct2/show/NCT05765877
Conditions:Non-Small Cell Lung Cancer(NSCLC)
Title:An Exploratory Study of Efficacy and Safety of Iruplinalkib Tablets in Patients With ROS1 Positive Non-small Cell Lung Cancer
Status:Recruiting
updateDate:2024-05-31
Ctid:NCT06436885
Link: https://clinicaltrials.gov/ct2/show/NCT06436885
Conditions:Non-Small Cell Lung CancerLink: https://clinicaltrials.gov/ct2/show/NCT06282536
Conditions:Potentially Resectable ALK Positive Non-Small Cell Lung CancerLink: https://clinicaltrials.gov/ct2/show/NCT04632758
Conditions:Non-small Cell Lung CancerLink: https://clinicaltrials.gov/ct2/show/NCT05991895
Conditions:Non-small Cell Lung Cancer (NSCLC)Link: https://clinicaltrials.gov/ct2/show/NCT05801107
Conditions:Non-small Cell Lung CancerLink: https://clinicaltrials.gov/ct2/show/NCT05351320
Conditions:Non-small Cell Lung Cancer (NSCLC)Link: https://clinicaltrials.gov/ct2/show/NCT04641754
Conditions:Non-small Cell Lung CancerLink: https://clinicaltrials.gov/ct2/show/NCT03389815
Conditions:Advanced Solid Tumor, Non-small Cell Lung CancerProducts are for research use only; We do not sell to patients
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