| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
|
NVP-CGM097 sulfate ( also known as CGM097; NVP-CGM-097; NVPCGM097), the sulfate salt of NVP-CGM097 or CGM-097, is a novel, orally bioavailable and selective inhibitor of MDM2 (human homolog of double minute 2)-p53 interaction with antitumor activity. With an IC50 of 1.7±0. nM, it blocks inhibits MDM2-p53.
| Targets |
hMDM2 (IC50 = 1.7±0.1 nM)
|
|---|---|
| ln Vitro |
NVP-CGM097 sulfate binds to human MDM2 with an IC50 of 1.7 nM and demonstrates strong selectivity for MDM4 (IC50=2000 nM). NVP-CGM097 sulfate is roughly four times more powerful than Nutlin-3a (IC50=8 nM). In addition, NVP-CGM097 sulfate showed no significant action on Bcl-2:Bak, Bcl-2:Bad, Mcl-1:Bak, Mcl-1:NOXA, XIAP:BIR3 and c-IAP:BIR3 protein-protein responses. CGM097 sulfate effectively reduced the growth of cells expressing wild-type p53 while sparing p53-null cells with a 35-58-fold differential. NVP-CGM097 sulfate may dramatically relocate wild-type p53 into the nucleus, with an IC50 of 0.224 μM, indicating that it can suppress NVP-CGM097 sulfate significantly reduces the proliferation of cells expressing wild-type p53, at a 35-58-fold rate. Differential retention of p53 null cells. NVP-CGM097 sulfate inhibits HCT116 (p53WT/WT) with an IC50 of 454±136nM[1].
|
| ln Vivo |
In the SJSA-1 human tumor model, NVP-CGM097 sulfate reactivates the p53 dye adjacent to MDM2 and suppresses the response between p53 and MDM2, as indicated by higher p21 mRNA levels, a measure of p53 activity according to pharmacodynamic (PD) indications. It was discovered that when NVP-CGM097 sulfate levels were raised to 30 mg/kg in the tumor-bearing state, p21 mRNA levels rose as well. The biphasic PD response lasts for a maximum of twenty-four hours. Comparable patterns were observed in the mRNA levels of other p53 target genes, including MDM2 and PUMA, which were assessed in concurrent samples. NVP-CGM097 sulfate administration on a daily basis dramatically and dose-dependently enhanced SJSA-1 tumor development. 20 mg/kg is a dose that can help stabilize the condition, and the antibiotic's AUC0–24 is 163 μM.h. The total blood clearance (CL) of NVP-CGM097 following intravenous injection is 5 mL/min/kg for mice, 7 mL/min/kg for rats, 3 mL/min/kg for dogs, and 4 mL/min/kg for monkeys. Dogs have a longer apparent terminal half-life (t1/2) than birds (20 hours), whereas rats and monkeys have a longer t1/2 (6–12 hours). NVP-CGM097 was well absorbed upon prototyping, with Tmax occurring in the range of 1 to 4.5 for all studied species [1].
|
| Cell Assay |
Two pairs of cell lines are used to assess NVP-CGM097 p53-dependent antiproliferative effects: (1) an isogenic pair of HCT116 cell lines either expressing wild-type p53 or knocked-out for the p53 gene and (2) a nonisogenic pair of osteosarcoma cell lines either endogenously expressing wild-type p53 and amplified for MDM2 (SJSA-1 cells) or null for p53 (SAOS-2 cells)[1].
|
| References |
[1]. Holzer P, et al. Discovery of a Dihydroisoquinolinone Derivative (NVP-CGM097): A Highly Potent and Selective MDM2 Inhibitor Undergoing Phase 1 Clinical Trials in p53wt Tumors. J Med Chem. 2015 Aug 27;58(16):6348-58
|
| Molecular Formula |
C₃₈H₄₉CLN₄O₈S
|
|---|---|
| Molecular Weight |
757.34
|
| Exact Mass |
756.296
|
| Elemental Analysis |
C, 60.27; H, 6.52; Cl, 4.68; N, 7.40; O, 16.90; S, 4.23
|
| CAS # |
1313367-56-4
|
| Related CAS # |
NVP-CGM097;1313363-54-0;NVP-CGM097 (stereoisomer);2070009-54-8
|
| Appearance |
Solid powder
|
| SMILES |
CC(C)OC1=C(C=C2CC(=O)N([C@H](C2=C1)C3=CC=C(C=C3)Cl)C4=CC=C(C=C4)N(C)CC5CCC(CC5)N6CCN(C(=O)C6)C)OC.OS(=O)(=O)O
|
| InChi Key |
YFLKIFVIZIALIA-GHVGLMRRSA-N
|
| InChi Code |
InChI=1S/C38H47ClN4O4.H2O4S/c1-25(2)47-35-22-33-28(20-34(35)46-5)21-36(44)43(38(33)27-8-10-29(39)11-9-27)32-16-14-30(15-17-32)41(4)23-26-6-12-31(13-7-26)42-19-18-40(3)37(45)24-42;1-5(2,3)4/h8-11,14-17,20,22,25-26,31,38H,6-7,12-13,18-19,21,23-24H2,1-5H3;(H2,1,2,3,4)/t26?,31?,38-;/m0./s1
|
| Chemical Name |
(1S)-1-(4-chlorophenyl)-6-methoxy-2-[4-[methyl-[[4-(4-methyl-3-oxopiperazin-1-yl)cyclohexyl]methyl]amino]phenyl]-7-propan-2-yloxy-1,4-dihydroisoquinolin-3-one;sulfuric acid
|
| Synonyms |
NVP-CGM097 sulfate; NVP CGM097 sulfate
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: ~100 mg/mL (132.0 mM)
H2O: ~100 mg/mL (132.0 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.30 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 50 mg/mL (66.02 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3204 mL | 6.6021 mL | 13.2041 mL | |
| 5 mM | 0.2641 mL | 1.3204 mL | 2.6408 mL | |
| 10 mM | 0.1320 mL | 0.6602 mL | 1.3204 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
