| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Voltage‑gated sodium channel NaV1.7 (human).
|
|---|---|
| ln Vitro |
Electrophysiology (manual patch clamp): HEK293 cells expressing human NaV1.7; GDC-0276 blocks peak current with IC50 = 0.4 nM (Hill coefficient 0.9). Selectivity: IC50 >1 uM for NaV1.1,1.2,1.3,1.4,1.5,1.6,1.8; >10 uM for NaV1.9 and hERG. No activity against a panel of 70 GPCRs, ion channels, and enzymes at 10 uM.
|
| ln Vivo |
GDC-0276 (Wall; 0.5–5 mg/kg) exhibits a specific activity of 22.6 μCi/mg and 14C enrichment. Guns tested negative for GDC-0276; nevertheless, stolen artifacts tested positive for 14C enrichment, with a specific activity of 19.6 μCi/mg [3].
In complete Freund's adjuvant (CFA)‑induced inflammatory pain rat model, oral GDC-0276 (3 mg/kg) produces full reversal of mechanical allodynia (paw withdrawal threshold from 5 g to 15 g, equal to baseline) for 6 h. In spared nerve injury (SNI) neuropathic pain model, ED50 = 1.2 mg/kg p.o. |
| Enzyme Assay |
Automated patch clamp (QPatch): cells held at -100 mV; test compound (0.01-100 nM) applied for 5 min; peak sodium current elicited by depolarization to 0 mV; currents normalized to vehicle control; IC50 derived from concentration‑response curve. Binding affinity measured by [3H]tetrodotoxin displacement; Ki = 0.3 nM.
|
| Cell Assay |
HEK293 NaV1.7 cells in 384‑well plates; after whole‑cell configuration, GDC-0276 perfused using a 16‑channel pipette; currents recorded at 10 kHz; IC50 calculated by Hill equation. Alternatively, use fluorescent membrane potential assay (FMP) with red dye; compound EC50 for inhibition of veratridine‑induced depolarization ~2 nM.
|
| Animal Protocol |
Animal/Disease Models: 6 drug-naïve beagles, 4 dogs in group 1 (n=2 of each sex) and 2 BDC dogs in group 2 (n=2 males) [3]
Doses: 0.5, 1 , 2, 3, 4, 5 mg/kg Route of Administration: Oral Experimental Results: Mean specific activity was 12.2 µCi/mg (24% enriched) (n=4 animals) and 23.5 µCi/mg Groups 1 and 2 mg (139% enrichment) for 2 groups respectively (n=2 animals). Rat CFA model: male SD rats injected with 50 uL CFA into left hind paw; after 24 h, baseline paw withdrawal threshold measured with von Frey filaments; rats randomized (n=8/group); given GDC-0276 (0.3-10 mg/kg p.o. in 0.5% methylcellulose); measurements at 0.5,1,2,4,6,8 h post‑dose; ED50 calculated using non‑linear regression. |
| ADME/Pharmacokinetics |
Rat p.o. 3 mg/kg: Cmax ~1.8 uM at 1 h; AUC ~11 uM·h; t1/2 ~4.5 h; oral bioavailability ~62%; plasma protein binding >99.5%; low brain exposure (brain/plasma 0.05); metabolized slowly by CYP3A4; major route excretion in feces (80%) as parent and hydroxylated metabolites.
|
| Toxicity/Toxicokinetics |
No significant adverse effects in rats at 100 mg/kg p.o. (single dose): no seizures, no motor impairment (rotarod test), no cardiovascular changes (telemetry). In dog 14‑day study (30 mg/kg/day), mild GI disturbance (loose stool) observed. No hERG inhibition (IC50 >30 uM). Genotoxicity negative.
|
| References |
|
| Additional Infomation |
Discontinued after Phase I due to inadequate exposure and target engagement in humans (high plasma protein binding limiting free fraction). However, remains a valuable research tool for NaV1.7 pharmacology and structure‑based drug design. Chemical structure published (WO2013/085074). Used to validate NaV1.7 as a human pain target.
|
| Molecular Formula |
C24H31FN2O4S
|
|---|---|
| Molecular Weight |
462.577348947525
|
| Exact Mass |
462.198
|
| CAS # |
1494581-70-2
|
| PubChem CID |
91809347
|
| Appearance |
White to off-white solid powder
|
| LogP |
4.7
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
32
|
| Complexity |
809
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
S(NC(C1=C(C=C(C(=C1)C1CC1)OCC12CC3CC(CC(C3)C1)C2)F)=O)(N1CCC1)(=O)=O
|
| InChi Key |
PTCBNPULJWGSML-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H31FN2O4S/c25-21-10-22(31-14-24-11-15-6-16(12-24)8-17(7-15)13-24)19(18-2-3-18)9-20(21)23(28)26-32(29,30)27-4-1-5-27/h9-10,15-18H,1-8,11-14H2,(H,26,28)
|
| Chemical Name |
4-(1-adamantylmethoxy)-N-(azetidin-1-ylsulfonyl)-5-cyclopropyl-2-fluorobenzamide
|
| Synonyms |
GDC0276; GDC 0276
|
| 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 : ~125 mg/mL (~270.22 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (13.51 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 62.5 mg/mL clear DMSO stock solution to 900 μL 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 | 2.1618 mL | 10.8089 mL | 21.6179 mL | |
| 5 mM | 0.4324 mL | 2.1618 mL | 4.3236 mL | |
| 10 mM | 0.2162 mL | 1.0809 mL | 2.1618 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
