[1]. Thappali SR, et al. Simultaneous Determination of Celecoxib, Erlotinib, and its Metabolite Desmethyl-Erlotinib (OSI-420) in Rat Plasma by Liquid chromatography/Tandem Mass Spectrometry with Positive/Negative Ion-Switching Electrospray Ionisation.Sci Pharm. 2012 Jul-Sep;80(3):633-46.
Linsitinib-d3 (OSI-906-d3) is the deuterium labeled Linsitinib. Linsitinib (OSI-906) is a potent, selective and orally bioavailable dual inhibitor of the IGF-1 receptor and insulin receptor (IR) with IC50s of 35 and 75 nM, respectively[1].
体外研究 (In Vitro)
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
424.51
Formula
C26H20D3N5O
CAS 号
1304632-17-4
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.
[2]. Mulvihill MJ, et al. Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and IR. Future Med Chem. 2009 Sep;1(6):1153-71.
[3]. McKinley ET, et al. 18FDG-PET predicts pharmacodynamic response to OSI-906, a dual IGF-1R/IR inhibitor, in preclinical mouse models of lung cancer. Clin Cancer Res. 2011 May 15;17(10):3332-40.
[4]. Li W, et al. Effectiveness of inhibitor rapamycin, saracatinib, linsitinib and JNJ-38877605 against human prostate cancer cells. Int J Clin Exp Med. 2015 Apr 15;8(4):6563-7.
Linsitinib-d3 (OSI-906-d3) is the deuterium labeled Linsitinib. Linsitinib (OSI-906) is a potent, selective and orally bioavailable dual inhibitor of the IGF-1 receptor and insulin receptor (IR) with IC50s of 35 and 75 nM, respectively[1].
体外研究 (In Vitro)
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
424.51
Formula
C26H20D3N5O
CAS 号
1304632-17-4
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.
[2]. Mulvihill MJ, et al. Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and IR. Future Med Chem. 2009 Sep;1(6):1153-71.
[3]. McKinley ET, et al. 18FDG-PET predicts pharmacodynamic response to OSI-906, a dual IGF-1R/IR inhibitor, in preclinical mouse models of lung cancer. Clin Cancer Res. 2011 May 15;17(10):3332-40.
[4]. Li W, et al. Effectiveness of inhibitor rapamycin, saracatinib, linsitinib and JNJ-38877605 against human prostate cancer cells. Int J Clin Exp Med. 2015 Apr 15;8(4):6563-7.
Linsitinib-d3 (OSI-906-d3) is the deuterium labeled Linsitinib. Linsitinib (OSI-906) is a potent, selective and orally bioavailable dual inhibitor of the IGF-1 receptor and insulin receptor (IR) with IC50s of 35 and 75 nM, respectively[1].
体外研究 (In Vitro)
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
424.51
Formula
C26H20D3N5O
CAS 号
1304632-17-4
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.
[2]. Mulvihill MJ, et al. Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and IR. Future Med Chem. 2009 Sep;1(6):1153-71.
[3]. McKinley ET, et al. 18FDG-PET predicts pharmacodynamic response to OSI-906, a dual IGF-1R/IR inhibitor, in preclinical mouse models of lung cancer. Clin Cancer Res. 2011 May 15;17(10):3332-40.
[4]. Li W, et al. Effectiveness of inhibitor rapamycin, saracatinib, linsitinib and JNJ-38877605 against human prostate cancer cells. Int J Clin Exp Med. 2015 Apr 15;8(4):6563-7.
Lurtotecan (GI147211; OSI-211) 是一种半合成喜树碱类似物,是一种拓扑异构酶 I (topoisomerase I) 抑制剂。Lurtotecan 具有抗癌作用。
Lurtotecan Chemical Structure
CAS No. : 149882-10-0
规格
是否有货
100 mg
询价
250 mg
询价
500 mg
询价
* Please select Quantity before adding items.
生物活性
Lurtotecan (GI147211; OSI-211), a semisynthetic Camptothecin analog, is a topoisomerase I inhibitor. Lurtotecan has anticancer effects[1].
IC50 & Target[1]
Topoisomerase I
分子量
518.56
Formula
C28H30N4O6
CAS 号
149882-10-0
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. D L Emerson, et al. In vivo antitumor activity of two new seven-substituted water-soluble camptothecin analogues. Cancer Res. 1995 Feb 1;55(3):603-9.
Lurtotecan (GI147211; OSI-211) 是一种半合成喜树碱类似物,是一种拓扑异构酶 I (topoisomerase I) 抑制剂。Lurtotecan 具有抗癌作用。
Lurtotecan Chemical Structure
CAS No. : 149882-10-0
规格
是否有货
100 mg
询价
250 mg
询价
500 mg
询价
* Please select Quantity before adding items.
生物活性
Lurtotecan (GI147211; OSI-211), a semisynthetic Camptothecin analog, is a topoisomerase I inhibitor. Lurtotecan has anticancer effects[1].
IC50 & Target[1]
Topoisomerase I
分子量
518.56
Formula
C28H30N4O6
CAS 号
149882-10-0
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. D L Emerson, et al. In vivo antitumor activity of two new seven-substituted water-soluble camptothecin analogues. Cancer Res. 1995 Feb 1;55(3):603-9.
Lurtotecan (GI147211; OSI-211) 是一种半合成喜树碱类似物,是一种拓扑异构酶 I (topoisomerase I) 抑制剂。Lurtotecan 具有抗癌作用。
Lurtotecan Chemical Structure
CAS No. : 149882-10-0
规格
是否有货
100 mg
询价
250 mg
询价
500 mg
询价
* Please select Quantity before adding items.
生物活性
Lurtotecan (GI147211; OSI-211), a semisynthetic Camptothecin analog, is a topoisomerase I inhibitor. Lurtotecan has anticancer effects[1].
IC50 & Target[1]
Topoisomerase I
分子量
518.56
Formula
C28H30N4O6
CAS 号
149882-10-0
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. D L Emerson, et al. In vivo antitumor activity of two new seven-substituted water-soluble camptothecin analogues. Cancer Res. 1995 Feb 1;55(3):603-9.
Thiarabine (OSI-7836) shows potent anti-tumor activity and inhibition of DNA synthesis.
IC50 & Target
DNA synthesis[1].
体内研究 (In Vivo)
Thiarabine has demonstrated exceptional antitumor activity against numerous human tumor xenografts in mice, being superior to gemcitabine, clofarabine, or cytarabine. Unlike cytarabine, Thiarabine demonstrates excellent activity against solid tumor xenografts, suggesting that this agent has the kind of robust activity in animal models that leads to clinical utility. Thiarabine is effective orally (bioavailability of approximately 16%) and with once per day dosing: Two characteristics that distinguish it from cytarabine. Although both the structure and basic mechanism of action of Thiarabine are similar to that of cytarabine, there are many quantitative differences in the biochemical pharmacology of these two agents that can explain the superior antitumor activity of Thiarabine. Two important attributes are the long retention time of the 5′-triphosphate of thiarabine in tumor cells and its potent inhibition of DNA synthesis. The biochemical pharmacology of Thiarabine is also different from that of gemcitabine[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
259.28
Formula
C9H13N3O4S
CAS 号
26599-17-7
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
参考文献
[1]. Parker WB, et al. Thiarabine, 1-(4-Thio-β-D-arabinofuranosyl)cytosine. A Deoxycytidine Analog With Excellent Anticancer Activity. Curr Med Chem. 2015;22(34):3881-96.
OSI-027 (ASP7486) is a potent, selective, orally active and ATP-competitive mTOR kinase activity inhibitor with an IC50 of 4 nM. OSI-027 targets both mTORC1 and mTORC2 with IC50s of 22 nM and 65 nM, respectively[1][2].
IC50 & Target[1]
mTOR
4 nM (IC50)
mTORC1
22 nM (IC50)
mTORC2
65 nM (IC50)
PI3K-γ
0.42 μM (IC50)
PI3K-α
1.3 μM (IC50)
DNA-PK
1 μM (IC50)
Autophagy
体外研究 (In Vitro)
OSI-027 is an ATP-competitive inhibitor, which targets both mTORC1 and mTORC2 with IC50s of 22 nM and 65 nM. OSI-027 also inhibits PI3K-α, PI3K-γ and DNA-PK with IC50s of 1.3 μM, 0.42 μM and 1.0 μM. OSI-027 inhibits mTOR signaling of phospho-4E-BP1 with an IC50 of 1 μM[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Effects on GEO colorectal xenograft growth treated with Rapamycin or OSI-027 for 12 days are consistent with our in vitro experiments. Treatment with Rapamycin (20 mg/kg) inhibits phospho-S6 and phospho-4E-BP1, while Akt phosphorylation is increased by 29%. In contrast, OSI-027 (65 mg/kg) inhibits both mTORC1 and mTORC2 effectors. After 2 hours, decreased 4E-BP1, Akt, and S6 phosphorylation is observed and inhibition of S6 and Akt is sustained for 24 hours. The plasma drug concentration of OSI-027 inversely correlated with these effects on mTORC1 and mTORC2 signaling. The median plasma drug concentration with OSI-027 is 21.3 μM at 2 hours and 14.9 μM at 8 hours. The in vivo efficacy of OSI-027 plus Sunitinib is tested in H292 human lung and Ovcar-5 human ovarian xenograft tumors. H292 tumors, treated with OSI-027 (50 mg/kg) for 21 days have 61% median tumor growth inhibition for the duration of treatment (TGI). Sunitinib (40 mg/kg) for 21 days had 47% median TGI. Combining OSI-027 with Sunitinib, however, has a median TGI of 100% with 59% maximal tumor regression, a statistically significant improvement over either agent alone. Ovcar-5 xenograft tumors treated with OSI-027 or Sunitinib have a 55% and 68% median TGI, respectively. OSI-027 administered with Sunitinib has a significantly better median TGI of 100% with 38% maximal tumor regression[1]. In the Rapamycin (RAPA) group, three rats exhibit symptoms typical of LTx-aGVHD and die 27 to 35 days after liver transplantation (LT); the remaining five rats do not develop LTx-aGVHD symptoms and survive for more than 100 days. In contrast, seven rats in the OSI-027 group survive for more than 100 days without symptoms of LTx-aGVHD, and only one rat exhibits LTx-aGVHD symptoms and dies on day 33 after LT[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
406.44
Formula
C21H22N6O3
CAS 号
936890-98-1
运输条件
Room temperature in continental US; may vary elsewhere.
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
[1]. Falcon BL, et al. Reduced VEGF production, angiogenesis, and vascular regrowth contribute to the antitumor properties of dual mTORC1/mTORC2 inhibitors. Cancer Res. 2011 Mar 1;71(5):1573-83.
[2]. Mateo J, et al. A first in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies. Br J Cancer. 2016;114(8):889-896.
[3]. Zhang Y, et al. PP2AC Level Determines Differential Programming of p38-TSC-mTOR Signaling and Therapeutic Response to p38-Targeted Therapy in Colorectal Cancer. EBioMedicine. 2015 Nov 19;2(12):1944-56.
[4]. Zhi X, et al. OSI-027 modulates acute graft-versus-host disease after liver transplantation in a rat model. Liver Transpl. 2017 Sep;23(9):1186-1198.
Kinase Assay [1]
Assays of a panel of 40 other recombinant kinases including both protein and lipid kinases are performed at 100 mM ATP concentration by SelectScreen profiling service. A broad panel of kinases is tested at a single concentration of OSI-027 or OXA-01 (3 μM) to evaluate percent inhibition of each kinase or mutant variant, using the Ambit KinomeScan platform[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay [1]
To study the effect of drug treatment on cellular signaling, Ovcar-3 cells are plated in normal growth medium. After 24 hours, serum is removed and cells are serum-starved overnight. Rapamycin, OSI-027 and OXA-01 are solubilized in DMSO and added to cells at varying concentrations. After a two-hour incubation cells are growth factor stimulated with 10 ng/mL Insulin for 3 to 5 minutes, then rinsed with cold PBS and lysed[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Mice[1] For xenograft models, cells are harvested, implanted s.c. in the right flank of nu/nu CD-1 mice and tumor growth is analyzed. Mice bearing GEO xenografts are treated for 12 days with OSI-027 (65mg/kg) or vehicle and tumors collected at 2, 8, and 24 hours. Tumor growth inhibition and regression calculations are included. Rats[2] Specific pathogen-free female Lewis rats, male BN rats, male Lew-Tg(CAG-EGFP)YsRrrc rats and male Lew-TgYsRrrc rats are used. Orthotopic LT is undertaken. No antibiotics were used. Freshly prepared splenocytes (4×108, suspended in 500 μL PBS) of Lew-Tg YsRrrc rats are infused into each recipient via the dorsal penile vein immediately after LT (within 30 min). LTx-aGVHD model rats are divided into three experimental groups: RAPA (1 mg/kg), OSI-027 (1 mg/kg) or control (equal quantity of vehicle) groups; treatments are administered via the vena caudalis from day 7 to day 15.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Falcon BL, et al. Reduced VEGF production, angiogenesis, and vascular regrowth contribute to the antitumor properties of dual mTORC1/mTORC2 inhibitors. Cancer Res. 2011 Mar 1;71(5):1573-83.
[2]. Mateo J, et al. A first in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies. Br J Cancer. 2016;114(8):889-896.
[3]. Zhang Y, et al. PP2AC Level Determines Differential Programming of p38-TSC-mTOR Signaling and Therapeutic Response to p38-Targeted Therapy in Colorectal Cancer. EBioMedicine. 2015 Nov 19;2(12):1944-56.
[4]. Zhi X, et al. OSI-027 modulates acute graft-versus-host disease after liver transplantation in a rat model. Liver Transpl. 2017 Sep;23(9):1186-1198.
Linsitinib (OSI-906) is a potent, selective and orally bioavailable dual inhibitor of the IGF-1 receptor and insulin receptor (IR) with IC50s of 35 and 75 nM, respectively[1].
IC50 & Target
IC50: 35 nM (IGF-1R), 75 nM (InsR)[1]
体外研究 (In Vitro)
Linsitinib inhibits IGF-1R autophosphorylation and activation of the downstream signaling proteins Akt, ERK1/2 and S6 kinase with IC50 of 0.028 to 0.13 μM. Linsitinib enables an intermediate conformation of the target protein through interactions with the C-helix. Linsitinib displays favorable metabolic stability in liver microsomes. Linsitinib fully inhibits both IR and IGF-1R phosphorylation at a concentration of 1 μM. Linsitinib inhibits proliferation of several tumor cell lines including non-small-cell lung cancer and colorectal cancer (CRC) tumor cell line with EC50 of 0.021 to 0.810 μM[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Linsitinib inhibits tumor growth in an IGF-1R-driven xenograft mouse model, with 100% TGI and 55% regression at a dose of 75 mg/kg and 60% TGI and no regression at a dose of 25 mg/kg. Linsitinib administration induces different elimination half-lives of itself in dog, rat and mice, the elimination half-lives are 1.18 hours, 2.64 hours and 2.14 hours, respectively. Linsitinib administration at different single dose once-daily in femal Sprague-Dawley rat and femal CD-1 mouse reveal that the Vmax is not dose-proportional to Linsitinib dose. Linsitinib elevates the blood glucose levels at a dose of 25 mg/kg after 12 days administration. Linsitinib administration at a single dose of 75 mg/kg in IGF-1R-driven full-length human IGF-1R (LISN) xenograft mouse model achieve maximal inhibition of IGF-1R phosphorylation (80%) between 4 and 24 hours with plasma drug concentrations of 26.6-4.77 μM[1]. Linsitinib administered as a single dose of at 60 mg/kg in NCI-H292 xenografts mice inhibits uptake of glucose at 2, 4, and 24 hours post-treatment in vivo. Linsitinib inhibits the growth of tumors in NCI-H292 xenograft mouse model[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
421.49
Formula
C26H23N5O
CAS 号
867160-71-2
运输条件
Room temperature in continental US; may vary elsewhere.
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
[1]. Mulvihill MJ, et al. Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and IR. Future Med Chem. 2009 Sep;1(6):1153-71.
[2]. McKinley ET, et al. 18FDG-PET predicts pharmacodynamic response to OSI-906, a dual IGF-1R/IR inhibitor, in preclinical mouse models of lung cancer. Clin Cancer Res. 2011 May 15;17(10):3332-40.
[3]. Li W, et al. Effectiveness of inhibitor rapamycin, saracatinib, linsitinib and JNJ-38877605 against human prostate cancer cells. Int J Clin Exp Med. 2015 Apr 15;8(4):6563-7.
Kinase Assay [1]
Protein kinase assays are either performed in-house by ELISA-based assay methods (IGF-1R, IR, EGFR and KDR) or by a radiometric method with ATP at 100 µM concentration. In-house ELISA assays use poly(Glu:Tyr) as the substrate bound to the surface of 96-well assay plates and phosphorylation is detected using an antiphosphotyrosine antibody conjugated to horseradish peroxidase. The bound antibody is quantified using ABTS as the peroxidase substrate by measuring absorbance at 405/490 nm. All assays use purified recombinant kinase catalytic domains. Recombinant enzymes of human IGF-1R or EGFR are expressed as an NH2-terminal glutathione S-transferase fusion protein in insect cells and are purified in house. IC50 values are determined from the sigmoidal dose-response plot of percent inhibition versus log10 compound concentration. A minimum of three measurements, performed in duplicate, are carried out with in-house assays unless otherwise indicated. Linsitinib at a concentration of 1 µM is profiled versus a panel of kinases using the ProfilerProTM Kinase Selectivity Assay Kit.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay [1]
For assays of cell proliferation, cells are seeded into 96-well plates in appropriate media containing FCS 10% and incubated for 3 days in the presence of Linsitinib at various concentrations. Inhibition of cell growth is determined by luminescent quantitation of intracellular ATP content using CellTiterGlo. Data is presented as a fraction of maximal proliferation, calculated by dividing the cellular density in the presence of varying concentrations of Linsitinib by the cellular density of control cells treated with vehicle (DMSO) only.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Cells are harvested from cell culture flasks during exponential cell growth, washed twice with sterile PBS to a suitable concentration before subcutaneous implantation on the right flank of female nu/nu CD-1 mice. Tumors are established to 200±50 mm3 in size before randomization into treatment groups of eight mice each for efficacy studies. Linsitinib or vehicle is administered orally as indicated. The %TGI values indicated are the median %TGI over the entire dosing period. TGI of at lease 505 is considered significant. Growth delay is calculated as T-C shere T and C are the times in days for mean tumor size in the treated (T) and control (C) groups to reach 400% of the initial tumor volume. Cures are excluded from this calculation.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Mulvihill MJ, et al. Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and IR. Future Med Chem. 2009 Sep;1(6):1153-71.
[2]. McKinley ET, et al. 18FDG-PET predicts pharmacodynamic response to OSI-906, a dual IGF-1R/IR inhibitor, in preclinical mouse models of lung cancer. Clin Cancer Res. 2011 May 15;17(10):3332-40.
[3]. Li W, et al. Effectiveness of inhibitor rapamycin, saracatinib, linsitinib and JNJ-38877605 against human prostate cancer cells. Int J Clin Exp Med. 2015 Apr 15;8(4):6563-7.
Apicidin (OSI 2040) is a fungal metabolite, acts as a histone deacetylase (HDAC) inhibitor, with antiparasitic activity and a broad spectrum antiproliferative activity[1].
IC50 & Target
HDAC[1]
分子量
623.78
Formula
C34H49N5O6
CAS 号
183506-66-3
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
In solvent
-80°C
6 months
-20°C
1 month
参考文献
[1]. Han JW, et al. Apicidin, a histone deacetylase inhibitor, inhibits proliferation of tumor cells via induction of p21WAF1/Cip1 and gelsolin. Cancer Res. 2000 Nov 1;60(21):6068-74.
OSI-930 is an orally selective inhibitor of Kit, KDR and CSF-1R (c-Fms) with IC50s of 80 nM, 9 nM and 15 nM, respectively. OSI-930 also moderately inhibits Flt-1, c-Raf, Lck and low activity against PDGFRα/β, Flt-3 and Abl. OSI-930 has antitumor activity[1].
IC50 & Target
KDR
9 nM (IC50)
Flt-1
8 nM (IC50)
Kit
80 nM (IC50)
PDGFRβ
6900 nM (IC50)
PDGFRα
3408 nM (IC50)
CSF-1R
15 nM (IC50)
c-Raf
41 nM (IC50)
Flt-3
1303 nM (IC50)
Lck
22 nM (IC50)
Abl
4738 nM (IC50)
体外研究 (In Vitro)
OSI-930 inhibits cell proliferation in the HMC-1 cell line with IC50 of 14 nM but has no significant effect on the growth of COLO-205 cell line that does not express constitutively active mutant receptor tyrosine kinase[1]. OSI-930 induces apoptosis in HMC-1 cell line with an EC50 value of 34 nM[1]. OSI-930 inactivates purified, recombinant cytochrome P450 3A4 with a Ki of 24 μM in a time- and concentration-dependent manner[2]
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
OSI-930 (oral gavage; once a day; 38 days; 200 mg/kg) exhibits potent antitumor activity in a broad range of preclinical xenograft models[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
[1]. Garton AJ, et al. OSI-930: a novel selective inhibitor of Kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models. Cancer Res. 2006, 66(2):1015-1024.
[2]. Lin HL, et al. Inactivation of cytochrome P450 (P450) 3A4 but not P450 3A5 by OSI-930, a thiophene-containing anticancer drug. Drug Metab Dispos. 2011, 39(2), 345-350.