BMS-536924 is an ATP-competitive IGF-1R/IR inhibitor with IC50 of 100 nM/73 nM.IC50 value: 100 nM (IGF-1R); 73 nM (IR) [1]Target: IGF-1R; IRin vitro: BMS-536924 also inhibits FAK and Lck with IC50 of 150 nM and 341 nM, respectively. BMS-536924 inhibits cellular proliferation and disrupts Akt and MAPK phosphorylation [1]. BMS-536924 inhibits IGF-I-stimulated IGF-1R signaling in MCF10A cells and blocks constitutive IGF-1R activity in CD8-IGF-1R-MCF10A. Preincubation of MCF10A cells with 1 μM BMS-536924 completely blocks the ability of IGF-I to stimulate IGF-1R phosphorylation. IGF-I stimulation results in increased phosphorylation of ERK1/2, GSK3β, and Akt. BMS-536924 inhibits this ligand-induced phosphorylation. Treatment of the CD8-IGF-1R-MCF10A cells with BMS-536924 results in a dose-dependent inhibition of phosphorylation with partial inhibition at 0.01 μM and 0.1 μM, but complete receptor inhibition at a concentration of 1 μM. Maximal inhibition of phosphorylated IGF-1R is observed as early as 10 minutes following incubation. BMS-536924 retains its ability to inhibit IGF-1R phosphorylation for up to 48 hours. Addition of BMS-536924 time-dependently inhibits Akt phosphorylation starting at 1 hour. By 48 hours, Akt activation is completely blocked [2]. in vivo: Oral administration of BMS-536924 at 100-300 mpk strongly inhibits IGR-1R Sal tumor model. Efficacy is also observed in the nonengineered Colo205 human colon carcinoma mode. Oral administration of 3 on a once a day schedule (100-300 mpk) or a twice a day schedule (50, 100 mpk) demonstrates antitumor activity in this tumor model. Oral glucose tolerance test (OGTT) shows 100 mpk (b.i.d.) causes a significant elevation in glucose levels after glucose challenge. The pharmacokinetic parameters of BMS-536924, administered orally in poly(ethylene glycol) 400 and water (80:20 v/v), are determined in mouse, rat, dog, and monkey. Good bioavailability is evident in all species. Significant nonlinear pharmacokinetics is observed in rodents at increasing p.o. dose [1]. Oral administration of 70 mg/kg BMS-536924 significantly inhibits tumor growth (TGBC-1TKB cells) inoculated in nude mice. BMS-536924 up regulates apoptosis in xenografts tumors. The treatment doesn't have adverse effects on the body weight of mice or the glucose levels at the time of death, suggesting tolerable toxicity [3].
Insulin(human) is a peptide hormone that regulates the level of sugar (glucose) in the blood and that is produced by the beta cells of the pancreatic islets.
S961 is an high-affinity and selective insulin receptor (IR) antagonist with IC50s of 0.048, 0.027, and 630 nM for HIR-A, HIR-B, and human insulin-like growth factor I receptor (HIGF-IR) in SPA-assay, respectively[1].
ERK Inhibitor II (Negative control) is an effective inhibitor of extracellular signal-regulated kinase (ERK). ERK Inhibitor II (Negative control) inhibits the activation of insulin receptor, which can be used in the study of diabetes[1][2].
[Tyr0] Gastric Inhibitory Peptide (23-42), human, a glucose-dependent insulinotropic polypeptide (GIP), is a weak inhibitor of gastric acid secretion that also stimulates insulin secretion. [Tyr0] Gastric Inhibitory Peptide (23-42), human can be used in diabetes, obesity research[1][2].
NVP-AEW541 is a potent inhibitor of IGF-1R with IC50 of 0.15 μM, also inhibits InsR, with IC50 of 0.14 μM.
NT157is a selective inhibitor of IRS-1/2, IC50 values at sub-micromolar doses (ranging from 0.3 to 0.8 μM) .IC50 value: 0.3 to 0.8 μM [1]Target: Insulin receptorin vitro: NT157 significantly affects the cells' migratory ability, as confirmed by a wound-healing assay. NT157 induces cytostatic effects, as evidenced by G2/M cell cycle arrest, and does not affect apoptosis. NT157, a novel small-molecule that specifically targets IRS protein, in OS cells. NT157 is a small-molecule inhibitor that induces Ser-phosphorylation and consequently the degradation of IRS-1 and IRS-2. NT157 efficiently affects migration ability of MG-63 and U-2OS OS cells. NT157 treatment induces cell cycle arrest and inhibits IGF system signaling. [1] The density of LNCaP cells grown in FBS was decreased approximately 20% at 1 μM, approximately 70% at 2 μM, and >90% at 5 μM (IC50, 1.4 μM). Growth of LNCaP cells is suppressed >60% when cultured in CSS but still exhibited significant density at 2 μM and maximal decreased density at 5 μM. The density of FBS-cultured PC3 cells was similarly decreased by NT157 treatment (40% at 2 μM and > 70% at 5 μM; IC50, 2.5 μM). [2]in vivo: NT157 suppresses growth of LNCaP xenografts following castration. NT157 treatment affects IGF1R and IRS targets in xenografts and significantly delays castration-resistant progression of LNCaP androgen-responsive xenografts when combined with castration. NT157 potentiates docetaxel activity in PC3 xenografts.[2]
GIP (3-42), human acts as a glucose-dependent insulinotropic polypeptide (GIP) receptor antagonist, moderating the insulin secreting and metabolic actions of GIP in vivo[1].
AGL-2263 is an insulin receptor (IR) blocker.
(Pro3) GIP, human ((Pro3) Gastric Inhibitory Peptide, human) is an efficacious, stable and specific human GIP receptor (hGIPR) full agonist. (Pro3) GIP, human has high binding affinity for human GIPR with Ki/ Kd values of 0.90 nM. (Pro3) GIP, human can be used for the research of obesity-related diabetes[1][2].
Insulin glulisine (HMR 1964) is a rapid-acting insulin analogue, it mimics the pharmacokinetic and pharmacodynamic profiles of physiological human insulin. Insulin glulisine can be used for the research of diabetes[1].
[D-Ala2]-GIP (human) is a GIP receptor agonist. [D-Ala2]-GIP (human) improves glucose tolerance. [D-Ala2]-GIP (human) shows neuroprotective activity in MPTP-induced Parkinson's disease model. [D-Ala2]-GIP (human) also improves cognitive function and hippocampal synaptic plasticity in obese diabetic rats. [D-Ala2]-GIP (human) can be used for research of type 2 diabetes, Parkinson's disease, etc[1]
Insulin efsitora alfa (LY-3209590) is a selective agonist of insulin receptor (IR). Insulin efsitora alfa is a fusion protein composed of human IR agonists fused with the crystallizable (Fc) domain of human immunoglobulin G2 (IgG2) fragment, with a molecular weight of 64.1 kDa. Insulin efsitora alfa is well tolerated and has potential applications in diabetes patients[1].