cLogP was calculated using http://bleoberis.bioc.cam.ac.uk/pkcsm/prediction .46 (link) cLogS and cLogD were calculated as a function of pH using https://disco.chemaxon.com/apps/demos/ . Pharmacokinetic properties were calculated using http://bleoberis.bioc.cam.ac.uk/pkcsm/prediction , as described by Pires et al.47 (link)The in vivo pharmacokinetics and in vitro preclinical testing of compound 30 was measured by GVK Biosciences Private Limited, Hyderabad, India using a protocol we described previously.42 (link) The vehicle used was 15%DMSO (in which the compound was initially dissolved, containing 10 equivalents of aq. NaHCO3), 15% Kolliphor® ELP (Sigma 30906, CAS 61791–12-6), 70% PBS, at a max. concentration of 2 mg/mL for the highest p.o. dose of 10 mg/kg.
Kolliphor elp
Manufactured by Merck Group
Sourced in India, Italy
Kolliphor ELP is a non-ionic solubilizing agent and emulsifier used in the formulation of pharmaceutical and cosmetic products. It is a water-soluble, polyethylene glycol-based compound that can improve the solubility and bioavailability of hydrophobic active ingredients.
Automatically generated - may contain errors
4 protocols using kolliphor elp
1
Preclinical Pharmacokinetics of Compound 30
2
Nude Mice Xenograft Tumor Growth Inhibition
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Athymic Balb/c nude mice were purchased from Charles River. Mice were housed 5 per cage with microisolater tops and provided food (Furina mice chow) and water ad libitum. The light cycle was regulated automatically (12 hours light/dark cycle) and temperature 23±1°C. Animals were allowed to acclimate to this environment for one week prior to usage. The Georgetown University Animal Care and Use Committee approved all animal studies in accordance with NIH guidelines. The stock solution of NSC 35446 hydrochloride was dissolved in DMSO at 200 mg/ml. The working solution was prepared using 10% Kolliphor ELP (Sigma-Aldrich), 3% PEG400 (Hampton Research, HR2-603); and 87% PBS to give a 1 mg/ml solution. Female Balb/c nude mice (18-22g) were injected with LCC9 cells (3 × 106 cells in a volume of 0.3 ml) in the subcutaneous tissue of the right axillary region. The mice were randomly sorted into groups with N=5 mice per group; and treatments were initiated when the tumors reached 150-200 mm3. The tumor-bearing mice were given intraperitoneal injections of vehicle only (control), 5 mg/kg, 10 mg/kg, or 20 mg/kg of NSC 35446 hydrochloride every other day. The tumor size of each mouse was measured by caliper and calculated by the formula: length × width × width/2 and the body weight was recorded.
3
Tannin-Based Sustainable Biopolymer Formulation
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Sulphited quebracho (Schinopsis lorentzii and Schinopsis balansae) tannin extract, called Fintan T, was kindly supplied by SilvaChimica (S. Michele Mondovi, Italy).
Furfuryl alcohol, Kolliphor ELP, glutarladehyde 50% water solution and glyoxal 40% water solution were provided by Sigma-Aldrich (France), and used as supplied.
Phenolsulphonic acid 65% water solution was purchased at Capital Resin Corporation (Columbus, OH, USA). Ethoxylated oleyl amine, OAM-10, was supplied by Saibaba Surfactants Ltd (Gujarat, India) and the foaming agent used was SM2101, a proprietary product supplied by Condat (Chasse-sur-Rhone, France) mainly composed of alkyl glycols and modified fatty acid soaps.
Furfuryl alcohol, Kolliphor ELP, glutarladehyde 50% water solution and glyoxal 40% water solution were provided by Sigma-Aldrich (France), and used as supplied.
Phenolsulphonic acid 65% water solution was purchased at Capital Resin Corporation (Columbus, OH, USA). Ethoxylated oleyl amine, OAM-10, was supplied by Saibaba Surfactants Ltd (Gujarat, India) and the foaming agent used was SM2101, a proprietary product supplied by Condat (Chasse-sur-Rhone, France) mainly composed of alkyl glycols and modified fatty acid soaps.
4
Evaluating CHK1 Inhibitor in BRCA-Deficient Tumors
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All animal procedures were performed in strict accordance with the Guide for the Care and Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee. Tumor xenografts were generated by injecting 2 × 10 6 MDA-MB-231 parental or shBRCA #4 breast cancer cells, in PBS with a final volume of 100 µL, into the left mammary fat pads of Ctrl: SHO-Prkdc SCID Hr Hr mice (Charles River Laboratories, Wilmington, MA, USA). In total, 12 mice were injected with MDA-MB-231 parental or shBRCA #4 cells and half of them (six mice) from particular transplantation was treated with the vehicle or CHK1 inhibitor SCH900776. Drug treatment began once a tumor had reached 0.03 cm 3 . The CHK1 inhibitor SCH900776 was dissolved in 20% Kolliphor ELP (Sigma-Aldrich, 30906) and administered intraperitoneally at a final concentration of 25 mg/kg for 5 days. This dose was selected based on a previously published study that investigated the same CHK1 inhibitor. 6 Two-dimensional calipers were used to measure tumor volumes during and after the treatment period, and volume was calculated based on the equation: π/6 × length × width 2 . 9 Data were normalized to the starting tumor volume of 0.03 cm 3 . The whole experiment was carried out in two independent replicates. Increase in tumor volume after the treatment was statistically analyzed by Student's t-test.
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