CJ-2360 is a potent oral ALK inhibitor (antagonist) with IC50s of 2.2, 4.0, 8.8, 6.3 and 8.9 nM against wild-type ALK and F1197M, G1269A, L1196M and S1206Y ALK mutants, respectively. CJ-2360 has strong inhibitory effect against two clinically reported ALK mutants (C1156Y and L1196M) and 468 kinases (LTK, MERTK, CLK1, DAPK1 and DAPK2).

Physicochemical Properties

Molecular Formula	C27H30FN5O2
Molecular Weight	475.56
Exact Mass	475.238
CAS #	2226742-61-4
PubChem CID	134524157
Appearance	Typically exists as solid at room temperature
LogP	5
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	3
Heavy Atom Count	35
Complexity	850
Defined Atom Stereocenter Count	2
SMILES	C[C@@H]1CN(C[C@@H](N1C)C)C2=C(C=C3C(=C2F)N(C4=C(C3=O)C5=C(N4)C=C(C=C5)C#N)C(C)C)OC
InChi Key	LOONVQWRKJLEEG-IYBDPMFKSA-N
InChi Code	InChI=1S/C27H30FN5O2/c1-14(2)33-24-19(26(34)22-18-8-7-17(11-29)9-20(18)30-27(22)33)10-21(35-6)25(23(24)28)32-12-15(3)31(5)16(4)13-32/h7-10,14-16,30H,12-13H2,1-6H3/t15-,16+
Chemical Name	4-fluoro-2-methoxy-11-oxo-5-propan-2-yl-3-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]-6H-indolo[2,3-b]quinoline-8-carbonitrile
HS Tariff Code	2934.99.9001
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)

Biological Activity

ln Vitro	In the KARPAS-299 cell line, CJ-2360 inhibits cell proliferation with an IC50 value of 1.8 nM. An IC50 value of 3 nM was determined from additional testing of CJ-2360's ability to suppress cell growth in the H3122 non-small-cell lung cell line harboring EML4-ALK. Mer tyrosine-protein kinase (MERTK), CLK1, DAPK1, DAPK2, and DAPK3 are all inhibited by CJ-2360, with IC50 values of 6.3, 11, 31, 23, 22, and 260 nM, in that order. CJ-2360 exhibits no discernible activity against IGF1R and >100-fold preference for ALK over insulin receptor kinase (INSR)[1].
ln Vivo	In the KARPAS-299 xenograft tumor model, CJ-2360 (100 mg/kg; po; twice daily for 22 days) can completely and permanently suppress tumor growth[1]. In KARPAS-299 tumor tissue, CJ-2360 (100 mg/kg; po) is particularly effective in inhibiting phosphorylation of ALK, ERK, and STAT3. This effect lasts for at least 24 hours[1].
Animal Protocol	Animal/Disease Models: KARPAS-299 xenograft model (female SCID mice)[1] Doses: 100 mg/kg Route of Administration: Po; twice (two times) daily for 22 days Experimental Results: Very efficacious in the KARPAS-299 xenograft model. It achieves complete tumor regression in 100% of tumors and all tumors did not return until day 53, 23 days after the last dose.
References	[1]. Discovery of CJ-2360 as a Potent and Orally Active Inhibitor of Anaplastic Lymphoma Kinase Capable of Achieving Complete Tumor Regression. J Med Chem. 2020;63(22):13994-14016.

Solubility Data

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

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1028 mL	10.5139 mL	21.0278 mL
	5 mM	0.4206 mL	2.1028 mL	4.2056 mL
	10 mM	0.2103 mL	1.0514 mL	2.1028 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.