CGP77675 hydrate is an orally bioavailable Src family kinase inhibitor. CGP77675 hydrate inhibits the phosphorylation of peptide substrates and the autophosphorylation of purified Src (IC50 is 5-20 and 40 nM, respectively), and also inhibits Src, EGFR, KDR, v-Abl and Lck with IC50 of 0.02, 0.15 and 0.15, respectively. 1.0, 0.31 and 0.29 μM. Has anti-tumor activity.

Physicochemical Properties

Molecular Formula	C26H29N5O2.XH2O
Related CAS #	CGP77675;234772-64-6
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: 0.02 μM (Src), 0.15 μM (EGFR), 1.0 μM (KDR), 0.31 μM (v-Abl), 0.29 μM (Lck)[1]
ln Vitro	At an IC50 of 5.5 nM for poly-Glu-Tyr and 16.7 nM for the optimal Src substrate (OSS) peptide, CGP77675 hydrate inhibits phosphorylation of both in a dose-dependent manner. Similar results were obtained using chicken Src (20 nM)[1], as indicated by these IC50 values. With a half-life of 0.8 micrometers, CGP77675 hydrate prevents bone resorption brought on by parathyroid hormone in rat fetal long bone cultures[1]. Src substrates Fak and paxillin are significantly less susceptible to CGP77675 hydrate (0.04-10 μM; 2 hours) than Src (IC50 values 0.2, 0.5, and 5.7 μM) in IC8.1 cells.
ln Vivo	CGP77675 hydrate (given subcutaneously, s.c., twice daily at 1, 5, and 25 mg/kg) prevents IL-1β-induced hypercalcemia in mice[1]. In young ovx rats, CGP77675 hydrate (10 and 50 mg/kg; given orally; twice daily for 6 weeks) recovers bone microarchitectural characteristics and largely prevents bone loss[1].
Cell Assay	Cell Viability Assay[1] Cell Types: MC3T3-E1 cells Tested Concentrations: 0.2, 1, and 5 μM Incubation Duration: 3 days Experimental Results: Did not influence cell viability for up to 3 days of treatment. Western Blot Analysis[1] Cell Types: Src-overexpressing IC8.1 cells Tested Concentrations: 0.04, 0.2, 1, 5, and 10 μM Incubation Duration: 2 hrs (hours) Experimental Results: Dose dependently inhibited phosphorylation of Fak and paxillin, but not of Src.
Animal Protocol	Animal/Disease Models: Male mice (Tif:MAGf; Novartis Animal Farm) of 25-30 g body[1] Doses: 1, 5, and 25 mg/kg Route of Administration: Injected sc; twice a day Experimental Results: Prevented IL-1β-induced hypercalcemia in mice without affecting serum amyloid protein levels. Animal/Disease Models: Eightweeks old (175-209 g) female rats of the Sprague- Dawley-derived strain Tif:RAlf[1] Doses: 10 and 50 mg/kg Route of Administration: Administered po (oral gavage) twice a day for 6 weeks Experimental Results: Partly prevented bone loss.
References	[1]. A novel inhibitor of the tyrosine kinase Src suppresses phosphorylation of its major cellularsubstrates and reduces bone resorption in vitro and in rodent models in vivo. Bone. 1999 May;24(5):437-49.

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.)