GDC-0276 is a potent, selective, reversible, orally bioactive NaV1.7 inhibitor (antagonist) with IC50 of 0.4 nM. GDC-0276 is well tolerated and displays favorable pharmacokinetic characteristics. GDC-0276 is indicated for pain and related research that addresses deficiencies in existing analgesic active molecules, like addiction and off-target side effects.

Physicochemical Properties

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)

Biological Activity

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].
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).
References	[1]. Safety, Tolerability, and Pharmacokinetics of GDC-0276, a Novel NaV1.7 Inhibitor, in a First-in-Human, Single- and Multiple-Dose Study i. [2]. Nav1.7 inhibitors for the treatment of chronic pain. Bioorganic & Medicinal Chemistry Letters (2018). [3]. Unequal Absorption of Radiolabeled and Nonradiolabeled Drug from the Oral Dose Leads to Incorrect Estimates of Drug Absorption and Circulating Metabolites in a Mass Balance Study.Drug Metab Lett. 2019;13(1):37-44.

Solubility Data

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.