| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
TRPA1[1].
|
|---|---|
| ln Vitro |
During the course of our research campaign, we identified an early lead molecule (1), which exhibited favorable in vitro TRPA1 potency as well as acceptable ADME properties across species. This lead was the result of an optimization campaign using ligand-based design, which focused on improving TRPA1 potency while lowering lipophilicity, and originated from a literature tool molecule. Given its overall promising physicochemical and in vitro profile coupled with demonstrated in vivo target engagement, we sought to benchmark this lead compound in exploratory toxicity studies to determine suitability for early development toward clinical use.[2]
|
| ln Vivo |
GDC-6599 is a potent, selective, and orally bioavailable TRPA1 small molecule antagonist with strong in vivo target engagement in rodent models. Several lead molecules in preclinical single- and short-term repeat-dose toxicity studies exhibited profound prolongation of coagulation parameters. Based on a thorough investigative toxicology and clinical pathology analysis, anticoagulation effects in vivo are hypothesized to be manifested by a metabolite─generated by aldehyde oxidase (AO)─possessing a similar pharmacophore to known anticoagulants (i.e., coumarins, indandiones). Further optimization to block AO-mediated metabolism yielded compounds that ameliorated coagulation effects in vivo, resulting in the discovery and advancement of clinical candidate GDC-6599, currently in Phase II clinical trials for respiratory indications.[2]
|
| References |
| Exact Mass |
426.121
|
|---|---|
| CAS # |
2376824-99-4
|
| PubChem CID |
139486484
|
| Appearance |
White to light yellow solid powder
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
30
|
| Complexity |
687
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CC1=NC2=C(C(=O)N1CC3=NC(=NO3)[C@H]4C[C@@H](OC4)C5=CC=C(C=C5)Cl)N(C=N2)C
|
| InChi Key |
FIBJEOLUMVIRIT-DZGCQCFKSA-N
|
| InChi Code |
InChI=1S/C20H19ClN6O3/c1-11-23-19-17(26(2)10-22-19)20(28)27(11)8-16-24-18(25-30-16)13-7-15(29-9-13)12-3-5-14(21)6-4-12/h3-6,10,13,15H,7-9H2,1-2H3/t13-,15+/m0/s1
|
| Chemical Name |
1-[[3-[(3R,5R)-5-(4-chlorophenyl)oxolan-3-yl]-1,2,4-oxadiazol-5-yl]methyl]-2,7-dimethylpurin-6-one
|
| 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 (~234.3 mM; with ultrasonication)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.86 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (5.86 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
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.
Link: https://clinicaltrials.gov/ct2/show/NCT05660850
Conditions:Chronic Refractory Cough (CRC) With Non-atopic Asthma|CRC With Atopic Asthma|Unexplained Chronic Cough|CRC With Chronic Obstructive Pulmonary Disease|CRC With Chronic Obstructive Pulmonary Disease With Chronic BronchitisProducts are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
