product name MGCD-265 analog
Description: MGCD-265 analog is a potent, orally bioavailable, multi-target and ATP-competitive inhibitor of c-Met and VEGFR1/2/3 with IC50 of 1 nM, 3 nM/3 nM/4 nM, respectively. MGCD265 analog has been studied in a variety of advanced solid tumors including NSCLC, as a monotherapy and in combination with either docetaxel or erlotinib. In a phase I study, MGCD265 analog was given orally from 24 mg/m2 daily to 235 mg/m2 twice daily uninterrupted to patients with advanced solid malignancy until disease progression.
References: Bioorg Med Chem Lett. 2008 May 1;18(9):2793-8; J Clin Oncol 28, 2010 (suppl; abstr e13595).
517.60
Formula
C26H20FN5O2S2
CAS No.
875337-44-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 104 mg/mL (200.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19402858
| In Vitro |
In vitro activity: MGCD-265 analog is a multi-target inhibitor of receptor tyrosine kinases. MGCD-265 analog potently inhibits Met, MetY1235D, MetM1250T, VEGFR1, VEGF2, VEGF3, Ron, and Tie2, with IC50 values ranging from 1 nM to 7 nM. MGCD-265 analog inhibits cell proliferation both in c-Met-driven tumor cells (MKN45, MNNG-HOS, and SNU-5) and in non-c-Met-driven tumor cells (HCT116 and MDA-MB-231), with IC50 values of 6 nM–30 nM and 1 μM–3 μM, respectively. In serum starved MKN45 cells, MGCD-265 analog(40 nM–5 μM) effectively inhibits c-Met phosphorylation and its downstream signaling pathways, including Erk, Akt, Stat3, and Fak. MGCD-265 analog (6 nM–1 μM) also induces apoptosis in MKN45 cells Kinase Assay: Cell Assay: Cells (HCT116, MDA-MB-231, SNU-5, and MKN45 cells) are treated with MGCD-265 analog for 72 hours and cell number is determined as a function of mitochondrial activity, following incubation with MTT for 4 hours. |
|---|---|
| In Vivo | In c-Met-driven or non-c-Met-driven mice xenograft models of MKN45, U87MG, MDA-MB-231, COLO205, and A549 tumor cells, MGCD-265 analog (20 mg/kg–60 mg/kg) inhibits tumor growth and c-Met signaling. MGCD-265 analog (40 mg/kg) also downregulates genes involved in angiogenesis, including VEGF and IL-8, both in tumor and plasma of mice with U87MG xenograft. MGCD-265 analog also inhibits the plasma level of shed-Met. |
| Animal model | |
| Formulation & Dosage | |
| References | J. M. Besterman, M. Fournel, I. Dupont, C. Bonfils, M. Dubay, H. Ste-Croix, C. R. Maroun; MethylGene, Inc., Montreal, QC, Canada, Potent preclinical antitumor activity of MGCD265, an oral Met/VEGFR kinase inhibitor in phase II clinical development, in combination with taxanes or erlotinib, J Clin Oncol 28, 2010 (suppl; abstr e13595). |
Related Posts
product name MGCD-265 analog
Description: MGCD-265 analog is a potent, orally bioavailable, multi-target and ATP-competitive inhibitor of c-Met and VEGFR1/2/3 with IC50 of 1 nM, 3 nM/3 nM/4 nM, respectively. MGCD265 analog has been studied in a variety of advanced solid tumors including NSCLC, as a monotherapy and in combination with either docetaxel or erlotinib. In a phase I study, MGCD265 analog was given orally from 24 mg/m2 daily to 235 mg/m2 twice daily uninterrupted to patients with advanced solid malignancy until disease progression.
References: Bioorg Med Chem Lett. 2008 May 1;18(9):2793-8; J Clin Oncol 28, 2010 (suppl; abstr e13595).
517.60
Formula
C26H20FN5O2S2
CAS No.
875337-44-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 104 mg/mL (200.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19402858
| In Vitro |
In vitro activity: MGCD-265 analog is a multi-target inhibitor of receptor tyrosine kinases. MGCD-265 analog potently inhibits Met, MetY1235D, MetM1250T, VEGFR1, VEGF2, VEGF3, Ron, and Tie2, with IC50 values ranging from 1 nM to 7 nM. MGCD-265 analog inhibits cell proliferation both in c-Met-driven tumor cells (MKN45, MNNG-HOS, and SNU-5) and in non-c-Met-driven tumor cells (HCT116 and MDA-MB-231), with IC50 values of 6 nM–30 nM and 1 μM–3 μM, respectively. In serum starved MKN45 cells, MGCD-265 analog(40 nM–5 μM) effectively inhibits c-Met phosphorylation and its downstream signaling pathways, including Erk, Akt, Stat3, and Fak. MGCD-265 analog (6 nM–1 μM) also induces apoptosis in MKN45 cells Kinase Assay: Cell Assay: Cells (HCT116, MDA-MB-231, SNU-5, and MKN45 cells) are treated with MGCD-265 analog for 72 hours and cell number is determined as a function of mitochondrial activity, following incubation with MTT for 4 hours. |
|---|---|
| In Vivo | In c-Met-driven or non-c-Met-driven mice xenograft models of MKN45, U87MG, MDA-MB-231, COLO205, and A549 tumor cells, MGCD-265 analog (20 mg/kg–60 mg/kg) inhibits tumor growth and c-Met signaling. MGCD-265 analog (40 mg/kg) also downregulates genes involved in angiogenesis, including VEGF and IL-8, both in tumor and plasma of mice with U87MG xenograft. MGCD-265 analog also inhibits the plasma level of shed-Met. |
| Animal model | |
| Formulation & Dosage | |
| References | J. M. Besterman, M. Fournel, I. Dupont, C. Bonfils, M. Dubay, H. Ste-Croix, C. R. Maroun; MethylGene, Inc., Montreal, QC, Canada, Potent preclinical antitumor activity of MGCD265, an oral Met/VEGFR kinase inhibitor in phase II clinical development, in combination with taxanes or erlotinib, J Clin Oncol 28, 2010 (suppl; abstr e13595). |