| Size | Price | Stock | Qty |
|---|---|---|---|
| 2mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
GDC-0152 (RG-7419) is a novel and potent antagonist of IAP (inhibitor of apoptosis) family proteins with antitumor activity. In cell-free assays, it inhibits IAPs with Kis of 28 nM, 14 nM, 17 nM, and 43 nM for XIAP-BIR3, ML-IAP-BIR3, cIAP1-BIR3, and cIAP2-BIR3, respectively; it has a lower affinity for cIAP1-BIR2 and cIAP2-BIR2. A Phase 1 clinical trial is looking into GDC-0152 as a potential cancer treatment.
| Targets |
MLXBIR3SG (Ki = 14 nM); cIAP1-BIR3 (Ki = 17 nM); XIAP-BIR3 (Ki = 28 nM); cIAP2-BIR3 (Ki = 43 nM); XIAP-BIR2 (Ki = 112 nM)
|
||
|---|---|---|---|
| ln Vitro |
GDC-0152 can block protein−protein interactions that involve IAP proteins and pro-apoptotic molecules. GDC-0152 is demonstrated to disrupt the association of ML-IAP, cIAP1, and cIAP2 with Smac as well as XIAP binding to partially processed caspase-9 using transiently transfected HEK293T cells. The endogenous association of ML-IAP and Smac is effectively also eliminated by GDC-0152 in melanoma SK-MEL28 cells. When compared to healthy human mammary epithelial cells (HMEC), GDC-0152 had no effect on HMEC but reduced cell viability in the MDA-MB-231 breast cancer cell line. It has been discovered that GDC-0152 activates caspases 3 and 7 in a dose- and time-dependent manner. In A2058 melanoma cells, GDC-0152 has been shown to cause cIAP1 to degrade rapidly. Its affinity for cIAP1 is supported by the fact that it successfully induces cIAP1 degradation at concentrations as low as 10 nM.
|
||
| ln Vivo |
GDC-0152 has moderate predicted hepatic clearance based on metabolic stability assays carried out using human liver microsomes.Over the range of concentrations investigated (0.1–100 μM), plasma protein binding of GDC-0152 is moderate and comparable in mice (88–91%), rats (89–91%), dogs (81–90%), monkeys (76–85%), and humans (75–83%); higher plasma protein binding is observed in rabbits (95–96%). In all tested species, GDC-0152 does not preferentially distribute to red blood cells with blood-plasma partition ratios ranging from 0.6 to 1.1. GDC-0152's pharmacokinetics are achieved with a Cmax of 53.7 μM and an AUC of 203.5 h•μM. [1]
|
||
| Enzyme Assay |
The IAP protein constructs are added to wells containing serial dilutions of the antagonists or the peptide AVPW, as appropriate, and the Hid-FAM probe or AVP-diPhe-FAM probe in the polarization buffer to determine the inhibitory constants (Ki) for the antagonists. After 30 minutes, samples are read. The IC50 values are calculated by fitting the data to a 4-parameter equation using software, and fluorescence polarization values are plotted as a function of antagonist concentration. Based on the IC50 values, the antagonists' Ki values are calculated.
|
||
| Cell Assay |
GDC-0152 is used to treat HMECs and MDA-MB-231 breast cancer cells in the recommended concentrations. The CellTiter-Glo luminescent cell viability assay is used to determine cell death 72 hours after the start of treatment.
|
||
| Animal Protocol |
|
||
| References | |||
| Additional Infomation |
GDC-0152 has been used in trials studying the treatment of Solid Cancers.
Smac Mimetic GDC-0152 is a second mitochondrial activator of caspases (Smac) mimetic inhibitor of IAPs (Inhibitor of Apoptosis Proteins) with potential antineoplastic activity. Smac mimetic GDC-0152 binds to the Smac binding groove on IAPs, including the direct caspase inhibitor X chromosome-linked IAP (XIAP) and the cellular IAPs 1 and 2, which may inhibit their activities and promote the induction of apoptosis through apoptotic signaling pathways. IAPs are overexpressed by many cancer cell types and suppress apoptosis by binding to and inhibiting active caspases-3, -7 and -9 via their baculoviral lAP repeat (BIR) domains. Smac, the endogenous IAP antagonist, relies on its N-terminal four amino-acid motif for binding to IAPs. |
| Molecular Formula |
C25H34N6O3S
|
|---|---|
| Molecular Weight |
498.64
|
| Exact Mass |
498.241
|
| Elemental Analysis |
C, 60.22; H, 6.87; N, 16.85; O, 9.63; S, 6.43
|
| CAS # |
873652-48-3
|
| Related CAS # |
873652-48-3;873581-21-6 (HCl);
|
| PubChem CID |
46940575
|
| Appearance |
White to off-white solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Index of Refraction |
1.606
|
| LogP |
2.09
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
35
|
| Complexity |
743
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
C(N1CCC[C@H]1C(=O)NC1SN=NC=1C1C=CC=CC=1)(=O)[C@H](C1CCCCC1)NC(=O)[C@H](C)NC
|
| InChi Key |
WZRFLSDVFPIXOV-LRQRDZAKSA-N
|
| InChi Code |
InChI=1S/C25H34N6O3S/c1-16(26-2)22(32)27-21(18-12-7-4-8-13-18)25(34)31-15-9-14-19(31)23(33)28-24-20(29-30-35-24)17-10-5-3-6-11-17/h3,5-6,10-11,16,18-19,21,26H,4,7-9,12-15H2,1-2H3,(H,27,32)(H,28,33)/t16-,19-,21-/m0/s1
|
| Chemical Name |
(2S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-(4-phenylthiadiazol-5-yl)pyrrolidine-2-carboxamide
|
| Synonyms |
GDC0152; GDC 0152; GDC0152; RG-7419; RG7419; RG 7419
|
| 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) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.01 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 (5.01 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 (5.01 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: 30% Propylene glycol , 5% Tween 80 , 65% D5W: 5mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0055 mL | 10.0273 mL | 20.0545 mL | |
| 5 mM | 0.4011 mL | 2.0055 mL | 4.0109 mL | |
| 10 mM | 0.2005 mL | 1.0027 mL | 2.0055 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00977067 | Terminated | Drug: GDC-0152 | Solid Cancers | Genentech, Inc. | June 2007 | Phase 1 |
|
|---|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
