[CAS NO. 1434635-54-7] Firsocostat
PRODUCTS SPECIFICATIONS [1434635-54-7]
DESCRIPTION [1434635-54-7]
Overview
| MDL | MFCD28963986 |
|---|---|
| Molecular Weight | 569.63 |
| Molecular Formula | C28H31N3O8S |
| SMILES | O=C(C(C(C)=C(C1=NC=CO1)S2)=C2N3C[C@H](OC4CCOCC4)C5=C(OC)C=CC=C5)N(C(C)(C)C(O)=O)C3=O |
7 Publications Citing Use of MCE
Summary
Firsocostat (ND-630; GS-0976; NDI-010976) is an acetyl-CoA carboxylase ( ACC ) inhibitor; inhibits human ACC1 and ACC2 with IC 50 values of 2.1 and 6.1 nM, respectively.
IC50 & Target
IC50: 2.1 nM (hACC1); 6.1 nM (hACC2) [1]
In Vitro
Firsocostat (ND-630) inhibits hACC1 (IC 50 =2.1±0.2 nM) and hACC2 (IC 50 =6.1±0.8 nM). Inhibition is reversible and highly specific for ACC. Firsocostat inhibits ACC activity by interacting within the phosphopeptide-acceptor and dimerization site of the enzyme to prevent dimerization. Firsocostat inhibits fatty acid synthesis with an EC 50 of 66 nM in HepG2 cells without altering the total cell number, cellular protein concentration, and incorporation of acetate into cholesterol [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Chronical administration of Firsocostat (ND-630) to rats with diet-induced obesity reduces hepatic steatosis, improves insulin sensitivity, reduces weight gain without affecting food intake, and favorably affects dyslipidemia. Chronical administration of Firsocostat Zucker diabetic fatty rats, Firsocostat reduces hepatic steatosis, improves glucose-stimulated insulin secretion, and reduces hemoglobin A1c (0.9% reduction). Firsocostat exhibits an aqueous solubility of 594 μM and human and rat plasma protein binding of 98.5% and 98.6%, respectively. Pharmacokinetic evaluation of Firsocostat in male Sprague-Dawley rats [i.v. 3 mg/kg; orally (p.o.) 10 mg/kg] yields a plasma t 1/2 of 4.5 h, bioavailability of 37%, clearance of 33 mL/min/kg, volume of distribution of 1.9 L/kg, oral time of maximum plasma concentration of 0.25 h [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT02856555 | Gilead Sciences |
Nonalcoholic Steatohepatitis (NASH)
|
August 8, 2016 | Phase 2 |
| NCT03987074 | Gilead Sciences|Novo Nordisk A+S |
Nonalcoholic Steatohepatitis
|
July 29, 2019 | Phase 2 |
| NCT02891408 | Gilead Sciences |
Nonalcoholic Steatohepatitis (NASH)
|
September 23, 2016 | Phase 1 |
| NCT02876796 | Gilead Sciences|Nimbus Apollo |
PD Effects of GS-0976 (NDI-010976) on Fractional DNL
|
August 2015 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 50 mg/mL ( 87.78 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.7555 mL | 8.7776 mL | 17.5553 mL |
| 5 mM | 0.3511 mL | 1.7555 mL | 3.5111 mL |
| 10 mM | 0.1756 mL | 0.8778 mL | 1.7555 mL |
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1.
Add each solvent one by one: 1% DMSO >> 99% saline
Solubility: 0.5 mg/mL (0.88 mM); Suspended solution; Need ultrasonic