CS-0117
BMS-536924
CAS: 468740-43-4
Molecular Formula: C25H26ClN5O3
CS-0117 - Names and Identifiers
CS-0117 - Physico-chemical Properties
| Molecular Formula | C25H26ClN5O3 |
| Molar Mass | 479.96 |
| Density | 1.44 |
| Melting Point | >206°C (dec.) |
| Solubility | DMSO: 89 mg/mL (185.4 mM)Ethanol: <1 mg/mLWater: <1 mg/mL( < 1 mg/ml refers to the product slightly soluble or insoluble) |
| Appearance | Solid |
| Color | Light Yellow to Yellow |
| pKa | 10.40±0.10(Predicted) |
| Storage Condition | Keep in dark place,Inert atmosphere,Store in freezer, under -20°C |
| Use | BMS-536924 is an orally active, competitive and selective insulin-like growth factor receptor (IGF-1R) kinase and insulin receptor (IR) inhibitor with IC50 of 100 nM and 73 nM, respectively. BMS-536924 has anti-cancer activity. |
| Target | FAK; IGF-1R; Insulin Receptor; Lck; MEK |
| In vitro study | BMS-536924 inhibition of FAK and Lck, The IC50 was 150 nM and 341 nM, respectively. BMS-536924 inhibits cell proliferation and interferes with Akt and MAPK phosphorylation. BMS-536924 inhibits IGF-I-stimulated IGF-1R signals in MCF10A cells and blocks essential IGF-1R activity in CD8-IGF-1R-MCF10A. Pre-incubation of MCF10A cells with 1 μm BMS-536924 completely blocked the ability of IGF-I to stimulate IGF-1R phosphorylation. IGF-I stimulation resulted in increased ERK1/2,GSK3β, and Akt phosphorylation. BMS-536924 inhibits phosphorylation induced by this ligand. BMS-536924 treatment of CD8-IGF-1R-MCF10A cells inhibited phosphorylation in a dose-dependent manner, with partial inhibition at 0.01 μm and 0.1 μm concentrations and complete inhibition of the receptor at 1 μm concentration. Maximum inhibition of phosphorylated IGF-1R was observed as early as after 10 min of incubation. Addition of BMS-536924 time-dependently inhibited the first 1 hour of Akt phosphorylation. By 48 hours, Akt activity was completely blocked. BMS-536924 treatment exhibited antiproliferative activity in a range of cancer cell lines, including TC32,HT1080/S,SK-LMS-1,H513 and CTR cells. In the Rh41 and Rh36 cell lines, pIGF-1R/pIR was activated based on IGF-I/insulin stimulation, and this activation was BMS-536924 to be inhibited with equal potency. BMS-536924 Rh41 cells were treated to upregulate the expression of programmed cell death 4 (PDCD4), and the cleavage of poly (ADP-ribose) polymerase (PARP) with caspase-3. |
| In vivo study | Oral administration of BMS-536924 at 100-300 mpk strongly inhibited the IGR-1R salamandal tumor model. This efficacy was also observed in the unengineered Colo 205 human colon cancer model. BMS-536924 oral administration, once a day for 3 courses (100-300 mpk), or twice a day for 1 course (50, 100 mpk) demonstrated antitumor activity in this tumor model. The oral glucose tolerance test (OGTT) showed that 100 mpk (B. I. d.) caused a significant increase in insulin levels after a glucose load. The pharmacokinetic parameters of BMS-536924 were determined in mice, rats, dogs, and monkeys by oral administration of poly (ethylene glycol) 400 and water (80:20 V/V). There is clearly good bioavailability in all species. In rodents with increasing oral doses, significant non-linear pharmacokinetics can be observed. After two weeks of treatment with BMS-536924(100 mg/kg), the xenograft volume of CD8-IGF-1R-MCF10A cells was reduced to 76%. Oral administration of 70 mg/kg BMS-536924 significantly inhibited tumor growth in nude mice inoculated with TGBC-1TKB cells. BMS-536924 upregulated apoptosis in transplanted tumors. The treatment had no adverse effects on the body weight or glucose levels of the mice at death, suggesting toxicity tolerance. |
CS-0117 - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.083 ml | 10.417 ml | 20.835 ml |
| 5 mM | 0.417 ml | 2.083 ml | 4.167 ml |
| 10 mM | 0.208 ml | 1.042 ml | 2.083 ml |
| 5 mM | 0.042 ml | 0.208 ml | 0.417 ml |
Last Update：2024-01-02 23:10:35
CS-0117 - Cell Experiment
Cell proliferation is evaluated by [3H]thymidine incorporation after exposure to BMS-536924 for 72 hours. Cells are plated at an optimized density in 96-well plates, incubated overnight at 37 °C, and then exposed to a serial dilution of the drug. After a 72-hours incubation, cells are pulsed with 4 μCi/mL [3H]thymidine for 3 hours Tropsinized, harvented onto UniFilter-96 GF/B platforms; Histology is measured. Results are expressed as an IC50. The mean IC50 and SD from multiple tests for each cell line are calculated. (Only for Reference) cell line: TC32, HT1080/S, SK-LMS-1, H513 and CTR cells
Last Update：2023-08-16 21:32:38
CS-0117 - Animal Experiment
Animal model: TGBC-1TKB.
Last Update：2023-08-16 21:32:38
CS-0117 - Reference Information
| Overview | insulin-like growth factor-1(insulin-likegrowthfactor-1,IGF-1) is a 70 amino acid polypeptide, it can affect the differentiation of cells and the survival of tissues in the animal body. The results of in vitro and in vivo experiments showed that IGF-1 had the same regulation effect on the reproductive axis, mainly reflected in the following three levels: IGF-1 was synthesized in ovarian tissue and involved in endocrine regulation in a paracrine manner; IGF-1 can inhibit the activity of pituitary growth hormone cells through endocrine action; IGF-1 of hypothalamus can affect growth hormone releasing hormone (GHRH) through Autocrine, paracrine or endocrine mode, somatostatin (SST) and GnRH neurons, thereby regulating the growth axis and reproductive axis. As with E2, IGF-1 is regulated through the IGF-1 receptor (IGF-1Receptor,IGF-1R). IGF-1 of the brain is one of the important regulators of reproductive neuroendocrine function, and IGF-1R is located in many tissues, such as ovary and brain. |
| effect | chronic intracerebroventricular injection of the highly selective insulin-like growth factor -1 receptor antagonist JB-1 inhibited E2-induced LH release and proconvex behavior. In ovariectomized rats without hormone replacement, JB-1 had no effect on LH release, indicating that JB-1 had an inhibitory effect on the positive feedback of E2. |
| biological activity | BMS-536924 (CS-0117) is a competitive IGF-1R inhibitor of ATP with IC50 of 100 nM, fak, and Lck also had moderate inhibitory activity, but had little inhibitory activity against Akt1, and MAPK1/2. |
| Target | Value |
| Insulin Receptor | 73 nM |
| IGF-1R () | 100 nM |
| FAK | 150 nM |
| MEK | 182 nM |
| LCK | 341 nM |
Last Update：2024-04-09 21:54:55
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Product Name: BMS-536924 Visit Supplier Webpage Request for quotationCAS: 468740-43-4
Tel: 609-228-6898
Email: sales@medchemexpress.com
tech@medchemexpress.com
Mobile: 609-228-6898
Spot supply
Product Name: BMS-536924 Visit Supplier Webpage Request for quotationCAS: 468740-43-4
Tel: +86-400-900-4166
Email: product@acmec-e.com
Mobile: +86-18621343501
QQ: 2881950922
Wechat: 18621343501
WhatsApp: +86-18621343501
Spot supply
Product Name: HY-10262 Visit Supplier Webpage Request for quotationCAS: 468740-43-4
Tel: +86-18821248368
Email: Int06@meryer.com
Mobile: +86-18821248368
QQ: 495145328
WhatsApp: +86-18821248368
Spot supply
Product Name: BMS-536924 Visit Supplier Webpage Request for quotationCAS: 468740-43-4
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
View History
CS-0117
Cyclopenta[b]pyrrole-1(2H)-carboxaldehyde, 3,3a,6,6a-tetrahydro-2-methyl- (9CI)
2-Benzhydryl-2-azaspiro[3.3]heptan-5-ol
2,6-二硝基苯酚
4-二碘四氟苯
(2R)-1-(3-氯-2-吡嗪基)-2-甲基哌嗪盐酸盐
[4R-[4a,5b,6b(R*)]]-3-二苯基磷酰氧基-6-(1-羟基乙基)-4-甲基-7-氧代-1-氮杂双环[3.2.0]庚-2-烯-2-羧酸对硝基苄酯
2(5H)-Furanone, 4,5-bis[(1-methylethyl)thio]-
2,2-二乙氧基丙烷,TECHNICAL GRADE
2,6-DIMETHYL-N-[4-(4-PENTYLCYCLOHEXYL)PHENYL]-4-MORPHOLINECARBOXAMIDE
Cyclopenta[b]pyrrole-1(2H)-carboxaldehyde, 3,3a,6,6a-tetrahydro-2-methyl- (9CI)
2-Benzhydryl-2-azaspiro[3.3]heptan-5-ol
2,6-二硝基苯酚
4-二碘四氟苯
(2R)-1-(3-氯-2-吡嗪基)-2-甲基哌嗪盐酸盐
[4R-[4a,5b,6b(R*)]]-3-二苯基磷酰氧基-6-(1-羟基乙基)-4-甲基-7-氧代-1-氮杂双环[3.2.0]庚-2-烯-2-羧酸对硝基苄酯
2(5H)-Furanone, 4,5-bis[(1-methylethyl)thio]-
2,2-二乙氧基丙烷,TECHNICAL GRADE
2,6-DIMETHYL-N-[4-(4-PENTYLCYCLOHEXYL)PHENYL]-4-MORPHOLINECARBOXAMIDE