Mifepristone-d3 (RU486-d3) is the deuterium labeled Mifepristone. Mifepristone (RU486) is a progesterone receptor (PR) and glucocorticoid receptor (GR) antagonist with IC50s of 0.2 nM and 2.6 nM in in vitro assay[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
432.61
Formula
C29H32D3NO2
CAS 号
1228097-18-4
中文名称
米非司酮 d3
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]. Jiang W, et al. New progesterone receptor antagonists: phosphorus-containing 11beta-aryl-substituted steroids. Bioorg Med Chem. 2006 Oct 1;14(19):6726-32.
[3]. Jurado R, et al. NSC 119875 cytotoxicity is increased by mifepristone in cervical carcinoma: an in vitro and in vivo study. Oncol Rep. 2009 Nov;22(5):1237-45.
[4]. Sharrett-Field L, et al. Mifepristone Pretreatment Reduces Ethanol Withdrawal Severity In Vivo. Alcohol Clin Exp Res. 2013 Aug;37(8):1417-23.
[5]. Yuehua You, et al. Progesterone Promotes Endothelial Nitric Oxide Synthase Expression Through Enhancing Nuclear Progesterone receptor-SP1 Formation. Am J Physiol Heart Circ Physiol. 2020 Jul 3.
RU-SKI 43 hydrochloride is a potent and selective Hedgehog acyltransferase (Hhat) inhibitor with an IC50 of 850 nM. RU-SKI 43 hydrochloride reduces Gli-1 activation through Smoothened-independent non-canonical signaling and decreases Akt and mTOR pathway activity. RU-SKI 43 hydrochloride has anti-cancer activity[1].
IC50 & Target
IC50: 850 nM (Hhat)[1]
体外研究 (In Vitro)
RU-SKI 43 hydrochloride (10 μM; for 6 days) strongly decreases cell proliferation (83% in AsPC-1 cells) in AsPC-1 and Panc-1 cells[2]. RU-SKI 43 hydrochloride (10 or 20 μM; 5 hours) causes dose-dependent inhibition of Shh palmitoylation following only 5 hours[1]. RU-SKI 43 hydrochloride (10 μM; for 72 hours) causes a 40% decrease in Gli-1 levels in AsPC-1 cells[2]. RU-SKI 43 hydrochloride (10 μM; 48 hours) results in decreased phosphorylation (47-67%) of four proteins in the Akt pathway, including Akt (phosphorylation at both Thr307 and Ser473), PRAS40, Bad and GSK-3β. RU-SKI 43 treatment also decreases phosphorylation of mTOR and S6, members of the mTOR signaling pathway[2]. RU-SKI 43 hydrochloride behaves as an uncompetitive inhibitor (Ki=7.4 μM) with respect to Shh, and as a noncompetitive inhibitor (Ki=6.9 μM) with respect to 125I-iodo-palmitoylCoA[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 Proliferation Assay[2]
Cell Line:
AsPC-1 and Panc-1 pancreatic cancer cells
Concentration:
10 μM
Incubation Time:
For 6 days (drugs were replenished every 48 hours)
Result:
Strongly decreased cell proliferation (83% in AsPC-1 cells).
Western Blot Analysis[1]
Cell Line:
COS-1 cells expressing HA-Hhat and Shh
Concentration:
10 or 20 μM
Incubation Time:
5 hours
Result:
Caused dose-dependent inhibition of Shh palmitoylation following only 5 hours.
体内研究 (In Vivo)
RU-SKI 43 hydrochloride has a t1/2 of 17 min in mouse plasma after IV administration[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
423.01
Formula
C22H31ClN2O2S
CAS 号
1782573-67-4
中文名称
RU-SKI 43(盐酸盐)
运输条件
Room temperature in continental US; may vary elsewhere.
RU-301 is a pan-TAM receptor inhibitor, exerts pan-TAM inhibitory activity by binding at the interface between Gas6 and the Ig1 domain of the respective TAMs with Kd and IC50 values of 12 μM and 10 μM, respectively[1].
IC50 & Target
IC50: 10 μM (TAM)[1]
分子量
480.46
Formula
C21H19F3N4O4S
CAS 号
1110873-99-8
运输条件
Room temperature in continental US; may vary elsewhere.
RU-SKI 43 is a potent and selective Hedgehog acyltransferase (Hhat) inhibitor with an IC50 of 850 nM. RU-SKI 43 reduces Gli-1 activation through Smoothened-independent non-canonical signaling and decreases Akt and mTOR pathway activity. RU-SKI 43 has anti-cancer activity[1].
IC50 & Target
IC50: 850 nM (Hhat)[1]
体外研究 (In Vitro)
RU-SKI 43 (10 μM; for 6 days) strongly decreases cell proliferation (83% in AsPC-1 cells) in AsPC-1 and Panc-1 cells[2]. RU-SKI 43 (10 or 20 μM; 5 hours) causes dose-dependent inhibition of Shh palmitoylation following only 5 hours[1]. RU-SKI 43 (10 μM; for 72 hours) causes a 40% decrease in Gli-1 levels in AsPC-1 cells[2]. RU-SKI 43 (10μM; 48 hours) results in decreased phosphorylation (47-67%) of four proteins in the Akt pathway, including Akt (phosphorylation at both Thr307 and Ser473), PRAS40, Bad and GSK-3β. RU-SKI 43 treatment also decreases phosphorylation of mTOR and S6, members of the mTOR signaling pathway[2]. RU-SKI 43 behaves as an uncompetitive inhibitor (Ki=7.4 μM) with respect to Shh, and as a noncompetitive inhibitor (Ki=6.9 μM) with respect to 125I-iodo-palmitoylCoA[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 Proliferation Assay[2]
Cell Line:
AsPC-1 and Panc-1 pancreatic cancer cells
Concentration:
10 μM
Incubation Time:
For 6 days (drugs were replenished every 48 hours)
Result:
Strongly decreased cell proliferation (83% in AsPC-1 cells).
Western Blot Analysis[1]
Cell Line:
COS-1 cells expressing HA-Hhat and Shh
Concentration:
10 or 20 μM
Incubation Time:
5 hours
Result:
Caused dose-dependent inhibition of Shh palmitoylation following only 5 hours.
体内研究 (In Vivo)
RU-SKI 43 has a t1/2 of 17 min in mouse plasma after IV administration[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
386.55
Formula
C22H30N2O2S
CAS 号
1043797-53-0
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]. Petrova E, et al. Inhibitors of Hedgehog acyltransferase block Sonic Hedgehog signaling.Nat Chem Biol. 2013 Apr;9(4):247-9.
[2]. Petrova E, et al. Hedgehog acyltransferase as a target in pancreatic ductal adenocarcinoma. Oncogene. 2014 Jan 27. doi: 10.1038/onc.2013.575.
RU-302 是一种非选择性的TAM 抑制剂,阻断 TAM Ig1 胞外域和 Gas6 Lg 结构域之间的界面。RU-302 用低微摩尔 IC50 有效阻断 Gas6 诱导的 Axl 受体活化,并有效抑制肺癌肿瘤的生长。
RU-302 Chemical Structure
CAS No. : 1182129-77-6
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
RU-302 is a pan TAM inhibitor that blocks the interface between the TAM Ig1 ectodomain and the Gas6 Lg domain. RU-302 effectively blocks Gas6-inducible Axl receptor activation with a low micromolar IC50in cell assays, and suppresses lung cancer tumor growth[1].
IC50 & Target
TAM, Axl[1]
分子量
475.53
Formula
C24H24F3N3O2S
CAS 号
1182129-77-6
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]. Kimani SG, et al. Small molecule inhibitors block Gas6-inducible TAM activation and tumorigenicity. Sci Rep. 2017 Mar 8;7:43908.
Mifepristone (RU486) is a progesterone receptor (PR) and glucocorticoid receptor (GR) antagonist with IC50s of 0.2 nM and 2.6 nM in in vitro assay[1].
IC50 & Target
IC50: 0.2 nM (progesterone receptor, in T47D cells), 2.6 nM (glucocorticoid receptor, in A549 cells)[1]
体外研究 (In Vitro)
The discovery of the first competitive progesterone antagonist, Mifepristone, has stimulated an intense search for more potent and more selective antiprogestins[1]. Cell growth is evaluated after 4 days of exposure to Mifepristone at 10 μM, a concentration close to the plasma concentration achievable in humans. The antiproliferative effect of NSC 119875 is potentiated when administered in combination with Mifepristone in HeLa cells. The IC50 of NSC 119875 in combination with Mifepristone is lower (14.2 μM) than that of NSC 119875 alone (34.2 μM) in HeLa cells with an approximately 2.5-fold difference. After treatment with Mifepristone, the accumulation of intracellular NSC 119875 in HeLa cells is 2-fold greater, representing a significant difference (p=0.009), compare with NSC 119875 alone from 0.79 to 1.52 μg/mg of protein[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)
The cervix tumor xenograft models are treated with NSC 119875 alone, there is a tumor growth inhibition compare with control group. However, the tumor weight loss is even more significant (p<0.05) with the combination of NSC 119875 and Mifepristone at the doses used, showing a decrease of ~50% compared with the treatments alone by the end of the study[2]. Adult male Sprague-Dawley rats are subjected to a 4-day binge-like EtOH administration regimen (3 to 5 g/kg/i.g. every 8 hours designed to produce peak blood EtOH levels (BELs) of <300 mg>[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
429.59
Formula
C29H35NO2
CAS 号
84371-65-3
中文名称
米非司酮;美服培酮
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
溶解性数据
In Vitro:
DMSO : 100 mg/mL (232.78 mM; ultrasonic and warming and heat to 60°C)
[1]. Jiang W, et al. New progesterone receptor antagonists: phosphorus-containing 11beta-aryl-substituted steroids. Bioorg Med Chem. 2006 Oct 1;14(19):6726-32.
[2]. Jurado R, et al. NSC 119875 cytotoxicity is increased by mifepristone in cervical carcinoma: an in vitro and in vivo study. Oncol Rep. 2009 Nov;22(5):1237-45.
[3]. Sharrett-Field L, et al. Mifepristone Pretreatment Reduces Ethanol Withdrawal Severity In Vivo. Alcohol Clin Exp Res. 2013 Aug;37(8):1417-23.
[4]. Yuehua You, et al. Progesterone Promotes Endothelial Nitric Oxide Synthase Expression Through Enhancing Nuclear Progesterone receptor-SP1 Formation. Am J Physiol Heart Circ Physiol. 2020 Jul 3.
Cell Assay [2]
The HeLa and CaSki human cervical cancer cell lines are used. The effect of Mifepristone on proliferation of cells exposed to NSC 119875 is evaluated using the XTT assay. The assay is based on the cleavage of the yellow tetrazolium salt XTT to form an orange formazan dye by metabolically active cells. The procedure is as follows. Cells are seeded into 96-well plates; Costar at a density of 6×103 viable cells per well in 100 μL culture medium. At the end of treatment with NSC 119875 alone or the combination of NSC 119875 plus Mifepristone, 50 μL XTT is added to each well (final concentration 0.3 mg/mL), follow by incubation for 4 h in a humidified atmosphere containing 5% CO2 at 37˚C. The absorbance of the samples is measured spectrophotometrically at 492 nm using a microtiter plate ELISA reader[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.
Animal Administration [2][3]
Mice[2] Female Nude mice between 6-8 weeks of age are implanted subcutaneously with 6×106 HeLa cells in a flank. Once tumors are ~5×5 mm, the animals are pair-matched into treatment and control groups. Each group consist of 8 tumor-bearing mice. The intraperitoneal administration of drugs or vehicle begin on day 0. NSC 119875, as a single agent, is administered intraperitoneally at a dose of 3 mg/kg daily on days 1 through 3; the dose of Mifepristone, as a single agent, is 2 mg/kg/day subcutaneously for 3 days; in the combination study, the mice concurrently receive NSC 119875 on the same schedule, and Mifepristone at the same dose 3 days previous to the administration of NSC 119875. The control animals receive only the vehicle. After administration of the drugs, mice are weighed and the tumors are measured with a caliper twice weekly. The tumor weight is calculated. Experiment is conducted for 74 days, after which time all animals are weighed and humanely euthanized. Rats[3] Adult male Sprague-Dawley rats, weighing between 224 and 245 g upon arrival, are used. Mifepristone (20 or 40 mg/kg) or vehicle (peanut oil) are administered subcutaneously (s.c.) once daily following the 0800 administration of EtOH or control diet. Mifepristone is suspended in peanut oil and sonicated for 30 minutes at least 24 hours prior to injection, it is then stored at 4°C until needed. Suspension is vortexed for 10 to 15 minutes prior to and as needed throughout dosing.
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]. Jiang W, et al. New progesterone receptor antagonists: phosphorus-containing 11beta-aryl-substituted steroids. Bioorg Med Chem. 2006 Oct 1;14(19):6726-32.
[2]. Jurado R, et al. NSC 119875 cytotoxicity is increased by mifepristone in cervical carcinoma: an in vitro and in vivo study. Oncol Rep. 2009 Nov;22(5):1237-45.
[3]. Sharrett-Field L, et al. Mifepristone Pretreatment Reduces Ethanol Withdrawal Severity In Vivo. Alcohol Clin Exp Res. 2013 Aug;37(8):1417-23.
[4]. Yuehua You, et al. Progesterone Promotes Endothelial Nitric Oxide Synthase Expression Through Enhancing Nuclear Progesterone receptor-SP1 Formation. Am J Physiol Heart Circ Physiol. 2020 Jul 3.
Halofuginone (RU-19110), a Febrifugine derivative, is a competitive prolyl-tRNA synthetase inhibitor with a Ki of 18.3 nM[1][2]. Halofuginone is a specific inhibitor of type-I collagen synthesis and attenuates osteoarthritis (OA) by inhibition of TGF-β activity[3][4]. Halofuginone is also a potent pulmonary vasodilator by activating Kv channels and blocking voltage-gated, receptor-operated and store-operated Ca2+ channels. Halofuginone has anti-malaria, anti-inflammatory, anti-cancer, anti-fibrosis effects[5].
IC50 & Target
Ki: 18.3±0.5 nM (prolyl-tRNA synthetase)[2]
体外研究 (In Vitro)
Halofuginone competitively inhibits prolyl-tRNA synthetase by occupying both the prolineand tRNA-binding pockets of prolyl-tRNA synthetase[1]. The IC50s of Halofuginone (1, 10, 100, 1000, 10000 nM; 48 hours) are 114.6 and 58.9 nM in KYSE70 and A549 cells, respectively. The IC50s of Halofuginone (1, 10, 100, 1000 nM; 24 hours) for NRF2 protein are 22.3 and 37.2 nM in KYSE70 and A549 cells, respectively. The IC50 of Halofuginone for global protein synthesis is 22.6 and 45.7 nM in KYSE70 and A549 cells, respectively[1]. Halofuginone increases voltage-gated K+ (Kv) currents in pulmonary artery smooth muscle cells (PASMC) and K+ currents through KCNA5 channels in HEK cells transfected with KCNA5 gene. Halofuginone (0.03-1μM) inhibits receptor-operated Ca2+ entry (ROCE) in HEK cells transfected with calcium-sensing receptor gene and attenuated store-operated (SOCE) Ca2+ entry in PASMC[5].
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 Viability Assay[1]
Cell Line:
KYSE70 cells from human oesophageal cancer harbouring a mutation in the NRF2 gene and A549 cells harbouring theKEAP1 gene mutation
Concentration:
1, 10, 100, 1000, 10000 nM
Incubation Time:
48 hours
Result:
The IC50s were 114.6 and 58.9 nM in KYSE70 and A549 cells, respectively.
Western Blot Analysis[1]
Cell Line:
KYSE70 cells from human oesophageal cancer harbouring a mutation in the NRF2 gene and A549 cells harbouring theKEAP1 gene mutation.
Concentration:
1, 10, 100, 1000 nM
Incubation Time:
24 hours
Result:
The IC50s for NRF2 protein were 22.3 and 37.2 nM in KYSE70 and A549 cells, respectively.
体内研究 (In Vivo)
Halofuginone (0.2, 0.5, 1 or 2.5 mg/kg; injected intraperitoneally every other day for 1 month) attenuates progression of OA in anterior cruciate ligament transection (ACLT) mice. Lower concentration (0.2 or 0.5 mg/kg) has minimal effects on subchondral bone and higher concentration (2.5 mg/kg) induces proteoglycan loss in articular cartilage[3]. Halofuginone (0.25 mg/kg; intraperitoneally injected; every day; 16 days) decreases NRF2 protein levels in tumors. While the tumor volumes do not change substantially between treatments with the vehicle, Halofuginone (0.25 mg/kg, intraperitoneally injected, every day) or cisplatin alone. Combined treatment with Halofuginone and Cisplatin significantly suppresses the tumor volume compared to treatment with Halofuginone or cisplatin alone[1]. Intraperitoneal administration of Halofuginone (0.3mg/kg, for 2 weeks) partially reverses the established pulmonary hypertension in mice[5].
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 Model:
3-month-old male C57BL/6J (WT) mice[3]
Dosage:
0.2, 0.5, 1 or 2.5 mg/kg
Administration:
Injected intraperitoneally every other day for 1 month
Result:
Attenuated progression of OA in ACLT mice.
Animal Model:
Male nude mice (BALB/C nu/nu mice) (6-8-week)[1]
Dosage:
0.25 mg/kg
Administration:
Intraperitoneally injected; every day; 16 days
Result:
The combined treatment with Cisplatin significantly suppressed the tumor volume. NRF2 protein levels in tumors were indeed decreased.
Clinical Trial
分子量
414.68
Formula
C16H17BrClN3O3
CAS 号
55837-20-2
中文名称
常山酮;卤夫酮;哈洛夫酮
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
溶解性数据
In Vitro:
DMSO : 20 mg/mL (48.23 mM; ultrasonic and adjust pH to 5 with HCl)
[1]. Tsuchida K, et al. Halofuginone enhances the chemo-sensitivity of cancer cells by suppressing NRF2 accumulation. Free Radic Biol Med. 2017 Feb;103:236-247.
[2]. Keller TL, et al. Halofuginone and other Febrifugine derivatives inhibit prolyl-tRNA synthetase. Nat Chem Biol. 2012 Feb 12;8(3):311-7.
[3]. Cui Z, et al. Halofuginone attenuates osteoarthritis by inhibition of TGF-β activity and H-type vessel formation in subchondral bone. Ann Rheum Dis. 2016 Sep;75(9):1714-21.
[4]. Tracy L McGaha, et al. Halofuginone, an inhibitor of type-I collagen synthesis and skin sclerosis, blocks transforming-growth-factor-beta-mediated Smad3 activation in fibroblasts. J Invest Dermatol. 2002 Mar;118(3):461-70.
[5]. Pritesh P Jain, et al. Halofuginone, a Promising Drug for Treatment of Pulmonary Hypertension. Br J Pharmacol. 2021 Mar 10.