| Targets |
The primary target of crizotinib, for which this compound serves as a building block, is the anaplastic lymphoma kinase (ALK) and the c‑ROS oncogene 1 (ROS1) receptor tyrosine kinases. Crizotinib binds competitively to the ATP‑binding pocket of these kinases, inhibiting their autophosphorylation and downstream signaling pathways (including PI3K/AKT, RAS/MAPK, and JAK/STAT), leading to cell cycle arrest and apoptosis in ALK‑ or ROS1‑driven tumors. This intermediate itself, however, does not have a defined pharmacological target; it is a chemical precursor.
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|---|---|
| ln Vitro |
The compound is not directly evaluated for in vitro biological activity, as it is a synthetic intermediate. It is used as a building block to assemble the crizotinib scaffold. The final drug crizotinib has been extensively characterized: it inhibits ALK with an IC₅0 of ~20 nM and ROS1 with an IC₅0 of ~100 nM. In cellular assays, crizotinib (0.1-10 uM) induces apoptosis and growth inhibition in ALK‑translocated cancer cell lines (e.g., NCI‑H3122, KARPAS‑299). However, this intermediate is not tested in such assays, as it lacks the necessary structural features for ATP‑competitive binding.
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| ln Vivo |
In vivo activity is associated with the final drug crizotinib, not with this intermediate. Crizotinib is approved for the treatment of ALK‑positive and ROS1‑positive NSCLC. In mouse xenograft models of ALK‑driven tumors (e.g., KARPAS‑299), oral administration of crizotinib (25-100 mg/kg daily) leads to significant tumor regression (≥80% inhibition) and prolonged survival. The intermediate is not administered in animals, as it is a process chemical that lacks pharmacological activity.
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| Enzyme Assay |
Non‑cell‑based experiments for this intermediate are analytical, to confirm its identity and purity. A typical HPLC method uses a chiral column (e.g., Chiralpak AD‑H, 4.6 × 250 mm, 5 um) with a mobile phase of hexane:isopropanol (90:10) at 0.8 mL/min, with UV detection at 254 nm, to determine enantiomeric excess (ee). For structural confirmation, ¹H NMR (400 MHz, DMSO‑d₆ or CDCl3) and LC‑MS (positive ESI mode, [M+H]+ expected at m/z 380.0/382.0, with characteristic isotopic patterns for Br and Cl) are standard.
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| Cell Assay |
Cell‑based assays are not applicable for this intermediate. The compound is a reagent used in chemical synthesis, not in cell culture. The free pyridine and primary amine groups may cause non‑specific cellular toxicity, but it is not designed or tested for cell‑based pharmacological studies. Any cell‑based evaluations of the final product would be performed on the fully elaborated drug, crizotinib.
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| Animal Protocol |
In vivo animal experiments are not conducted for this intermediate. It is not a drug candidate and is not administered to animals for therapeutic evaluation. The compound is intended solely for laboratory synthesis under fume hood conditions, not for in vivo use.
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| ADME/Pharmacokinetics |
Pharmacokinetic data are not applicable for this intermediate. The final drug crizotinib has an oral bioavailability of approximately 43%, a Tmax of 4-6 h, and a terminal elimination half‑life of 42 h in humans. Crizotinib is metabolized primarily by CYP3A4/5. This intermediate itself is a solid at room temperature (melting point not reported) and is soluble in organic solvents such as DMSO and DMF. It is typically stored at −20 degC in a sealed, dry container, protected from light.
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| Toxicity/Toxicokinetics |
The toxicity profile of this intermediate has not been characterized. As a research chemical, standard safety precautions apply. The compound contains bromine, chlorine, and fluorine atoms, which may contribute to toxicity. It should be handled in a well‑ventilated area (fume hood) with appropriate PPE (lab coat, gloves, safety goggles). The final drug crizotinib is generally well‑tolerated, with common adverse effects including nausea, diarrhea, vomiting, and visual disturbances. More serious toxicities include hepatotoxicity and interstitial lung disease.
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| Additional Infomation |
Additional information: The compound has an MDL number of MFCD18207061. It appears as a solid at 20 degC and has a purity of ≥98% from commercial suppliers. The product is for research and analytical applications only, not for human or veterinary use. It is also known as (R)-5‑bromo‑3‑(1‑(2,6‑dichloro‑3‑fluorophenyl)ethoxy)pyridin‑2‑amine and is used in the research of tyrosine kinase inhibitors (TKIs) for cancer therapy.
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| Exact Mass |
377.934
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|---|---|
| CAS # |
877399-00-3
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| PubChem CID |
11689426
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
20
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| Complexity |
329
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| Defined Atom Stereocenter Count |
1
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| InChi Key |
URFUZAZEKBBCEY-ZCFIWIBFSA-N
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| InChi Code |
InChI=1S/C13H10BrCl2FN2O/c1-6(11-8(15)2-3-9(17)12(11)16)20-10-4-7(14)5-19-13(10)18/h2-6H,1H3,(H2,18,19)/t6-/m1/s1
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| Chemical Name |
5-bromo-3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-2-amine
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| Synonyms |
(R)-5-bromo-3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-2-amine (Standard)
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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.) |
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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