Gemcabene (formerly known as PD-72953) is a potent and first-in-class lipid-lowering agent that lowers low-density lipoprotein cholesterol (LDL-C), decreases triglycerides, and raises high-density lipoprotein cholesterol (HDL-C) and lowers pro-inflammatory acute-phase protein, C-reactive protein (CRP), exerting anti-inflammatory activity.
Physicochemical Properties
| Molecular Formula | C16H30O5 |
| Molecular Weight | 302.4064 |
| Exact Mass | 302.209 |
| CAS # | 183293-82-5 |
| Related CAS # | Gemcabene calcium;209789-08-2 |
| PubChem CID | 157692 |
| Appearance | White to off-white solid powder |
| Density | 1.048g/cm3 |
| Boiling Point | 453.6ºC at 760mmHg |
| Flash Point | 156.7ºC |
| Vapour Pressure | 1.72E-09mmHg at 25°C |
| Index of Refraction | 1.473 |
| LogP | 3.565 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 12 |
| Heavy Atom Count | 21 |
| Complexity | 302 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O(CCCCC(C(=O)O)(C)C)CCCCC(C(=O)O)(C)C |
| InChi Key | SDMBRCRVFFHJKR-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C16H30O5/c1-15(2,13(17)18)9-5-7-11-21-12-8-6-10-16(3,4)14(19)20/h5-12H2,1-4H3,(H,17,18)(H,19,20) |
| Chemical Name | 6,6'-Oxybis(2,2-dimethylhexanoic acid) |
| Synonyms | PD72953; PD 72953; PD-72953; Gemcabene |
| 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) |
Biological Activity
| ln Vitro | Gemcabene Calcium (PD-72953 Calcium) markedly reduces the expression of mRNA markers associated with liver inflammation (TNF-α, MCP-1, MIP-1β, CCR5, CCR2, NF-κB), adipogenesis, and lipid regulation (ApoC-III, ACC1, ADH-4, Sulf-2) as well as fibrosis (TIMP-1 and MMP-2) [3]. |
| References |
[1]. Mandema JW, et al. Model-based development of gemcabene, a new lipid-altering agent. AAPS J. 2005 Oct 7;7(3):E513-22. [2]. Srivastava RAK, et al. Gemcabene, a First-in-Class Hypolipidemic Small Molecule in Clinical Development, Attenuates Osteoarthritis and Pain in Animal Models of Arthritis and Pain. Front Pharmacol. 2018 May 11;9:471. [3]. Oniciu DC, et al. Gemcabene downregulates inflammatory, lipid-altering and cell-signaling genes in the STAM™ model of NASH. PLoS One. 2018 May 30;13(5):e0194568. |
| Additional Infomation |
Gemcabene is a new drug that lowers low-density lipoprotein cholesterol (LDL-C), decreases triglycerides, and raises high-density lipoprotein cholesterol (HDL-C). Gemcabene is a dialkyl ether dicarboxylic acid with antihyperlipidemic activity. In animal models gemcabene increased high density lipoprotein (HDL) cholesterol levels and increased HDL particle size. Low-density lipoprotein cholesterol, trigylcerides, and apolipoprotein C-III levels were decreased as well. In human test subjects, the HDL lowering effect of gemcabene was only seen in patients with high (>200 mg/dl) levels of triglycerides. Drug Indication Investigated for use/treatment in atherosclerosis, cardiovascular disorders, and hyperlipidemia. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~330.68 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.27 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 (8.27 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (8.27 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3068 mL | 16.5338 mL | 33.0677 mL | |
| 5 mM | 0.6614 mL | 3.3068 mL | 6.6135 mL | |
| 10 mM | 0.3307 mL | 1.6534 mL | 3.3068 mL |