[CAS NO. 1496581-76-0] GNE-3511

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PRODUCTS SPECIFICATIONS [1496581-76-0]

Catalog

HY-12947

Brand

MCE

CAS

1496581-76-0

DESCRIPTION [1496581-76-0]

Overview

MDL	MFCD28502215
Molecular Weight	440.49
Molecular Formula	C23H26F2N6O
SMILES	N#CC1=CC=NC(NC2=NC(N3CC(F)(F)CC3)=CC(C4CCN(C5COC5)CC4)=C2)=C1

For research use only. We do not sell to patients.

6 Publications Citing Use of MCE

Summary

GNE-3511 is an orally active bioavailable and brain-penetrant dual leucine zipper kinase (DLK) inhibitor with a K _i of 0.5 nM. GNE-3511 can cross the blood-brain-barrier and can be used for the research of neurodegenerative diseases ^[1] .

IC50 & Target

Ki: 0.5 nM (DLK); IC50: 30 nM (p-JNK), 107 nM (DRG); ＞5000 nM (MKK4), ＞5000 nM (MKK7), 129 nM (JNK1),514 nM (JNK2), 364 nM (JNK3), 67.8 nM (MLK1), 767 nM (MLK2) and 602 nM (MLK3) ^[1]

In Vitro

GNE-3511 has inhibitory activity for p-JNK and DRG with IC ₅₀ values of 30 nM and 107 nM, respectively ^[1] .
GNE-3511 has kinase selectivity for MKK4, MKK7, JNK1, JNK2, JNK3, MLK1, MLK2 and MLK3 with IC ₅₀ values of ＞5000 nM, ＞5000 nM, 129 nM, 514 nM, 364 nM, 67.8 nM, 767 nM and 602 nM, respectively ^[1] .
GNE-3511 displays concentration-dependent protection of neurons from degeneration in vitro ^[1] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

GNE-3511 (oral gavage; 75 mg/kg; single) suppresses CYP-induced nociceptive behavior by inhibiting DLK in mice ^[2] .
GNE-3511 (oral gavage; 75 mg/kg; single) suppresses CYP-induced edema and hemorrhage in mouse bladder ^[2] .
GNE-3511 (iv.; 1 mg/kg or po.; 5 mg/kg) exhibits moderate in vivo plasma clearances, moderate volumes of distribution, short half-lives, and brain penetration ^[2] .
Pharmacokinetic Parameters of GNE-3511 (iv.; 1 mg/kg or po.; 5 mg/kg) ^[2] .

species	CL _p (mL/min/kg	Vd _ss (L/kg	t _1/2 (h)	F (%)	B _u /P _u	CSF/P _u
mouse	56	2.5	0.6	45	0.24 at 6 h
rat	30	3.7	1.8	63	0.7	0.4
dog	41	6.5	4	32		0.4
cynomolgous	16	3.1	2.4	19		0.6

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Cystitis mouse model ^[1]
Dosage:	75 mg/kg
Administration:	oral gavage;75 mg/kg; single
Result:	Significantly reduced the number of nociceptive behavior as well as nociceptive score. Had no impact on bladder weight, did not induce bladder edema or hemorrhage and significantly suppressed CYP-induced increase in bladder weight, bladder edema, and hemorrhage.

Animal Model:	mouse, rat, cynomolgus and dog ^[2]
Dosage:	1 mg/k, 5 mg/kg
Administration:	iv.; 1 mg/kg or po.; 5 mg/kg
Result:	Exhibited moderate in vivo plasma clearances, moderate volumes of distribution, short half-lives and brain penetration.

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

In Vitro:

DMSO : 31.25 mg/mL ( 70.94 mM ; Need ultrasonic)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.2702 mL	11.3510 mL	22.7020 mL
5 mM	0.4540 mL	2.2702 mL	4.5404 mL
10 mM	0.2270 mL	1.1351 mL	2.2702 mL

* Please refer to the solubility information to select the appropriate solvent.

In Vivo:

1.

Add each solvent one by one: 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline

Solubility: ≥ 2.08 mg/mL (4.72 mM); Clear solution

* All of the co-solvents are available by MCE.