D6808 is a selective c-Met inhibitor (antagonist) with IC50 of 2.9 nM. D6808 causes apoptosis and cell cycle arrest. D6808 may be utilized in the research of non-small cell lung cancer and gastric cancer.

Physicochemical Properties

Molecular Formula	C30H25F3N6O2
Molecular Weight	558.55
CAS #	3029240-84-1
Appearance	Typically exists as solid at room temperature
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

Targets	IC50: 2.9 nM (c‑Met)[1]
ln Vitro	D6808 exhibits 2.9 nM IC50 c-Met biochemical kinase inhibitory activity[1]. With an IC50 value of 0.7 nM, D6808 (0.0001-10 μM; 5 d) exhibits cellular antiproliferative efficacy against Hs746T cancer cells[1]. exhibits remarkable kinome selectivity, with IC50 values for Axl, TrkA, TrkB, and TrkC kinase, respectively, of 401.3, 437.2, 1386, and 203.9 nM[1]. With IC50 values of 4.3, 4.2, 3.2, 1.0, 39.0, and 33.4 nM for Ba/F3-Tpr-Met, Ba/F3-Tpr-MetF1200L, Ba/F3-Tpr-MetM1250T, Ba/F3 -Tpr-MetH1094Y, Ba/F3-Tpr-MetF1200I, and Ba/F3-Tpr-MetL1195V, respectively, D6808(0–10 μM; 72 h) exhibits antiproliferative potency to Tpr-Met fusion protein-transformed Ba/F3 cells[1]. In Ba/F3-Tpr-Met cells, D6808 (0-30 nM; 12 h) cleaves PARP and caspase-9 activation and dose-dependently reduces protein levels of CDK2, CDK4, CDK6, cyclin D2, and cyclin E1[1]. It also impacts MET activation. In Ba/F3-Tpr-Met cells, D6808 (40 nM; 24 h) causes 87.37% G0/G1 phase arrest and cell apoptosis[1].
ln Vivo	1.19 Rats' Pharmacokinetic Properties of D6808[1]. Fourth Rats Two milligrams per kilogram PO Rats 10.5 mg/kg IP Rats Tmax (h) 0.08 0.25 0.25 Cmax (ng/mL) 10.0 mg/kg T1/2 (h) 0.57 2.49 4.63 60.98 282.12 AUC0-T (h × ng/ml) 483.84 48.89 820.38 VZ (ML/KG) 3470.78 CL (ml/h/kg) 4207.06 MRT0-T (H) 0.71 3.40 F (%) 2.02 33.91
Cell Assay	Cell Proliferation Assay[1] Cell Types: Hs746T cancer cell line Tested Concentrations: 0.0001-10 μM Incubation Duration: 5 days Experimental Results: Inhibited the cell proliferation of Hs746T cancer cells. Western Blot Analysis[1] Cell Types: Hs746T and Ba/F3-Tpr-Met cell lines Tested Concentrations: 0, 0.37, 1.1, 3.3, 10 and 30 nM Incubation Duration: 12 hrs (hours) Experimental Results: Suppressed the activation of MET in Hs746T and Ba/F3-Tpr-Met cells. Apoptosis Analysis[1] Cell Types: Ba/F3-Tpr-Met cell line Tested Concentrations: 40 nM Incubation Duration: 24 hrs (hours) Experimental Results: Induced 50.89% apoptosis after 48 h treatment.
References	[1]. Discovery of D6808, a Highly Selective and Potent Macrocyclic c-Met Inhibitor for Gastric Cancer Harboring MET Gene Alteration Treatment. J Med Chem. 2022 Nov 24;65(22):15140-15164.

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	1.7904 mL	8.9518 mL	17.9035 mL
	5 mM	0.3581 mL	1.7904 mL	3.5807 mL
	10 mM	0.1790 mL	0.8952 mL	1.7904 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.