DN-1289

Cat. No.: HY-152142: FAQs
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DN-1289 is an orally active and selective inhibitor of dual leucine zipper kinase (DLK; IC₅₀=17 nM) and leucine zipper-bearing kinase (LZK; IC₅₀=40 nM). DN-1289 results significant attenuation of optic nerve crush (ONC)-induced p-c-Jun in mice model. DN-1289 has excellent in vivo plasma half-life and blood-brain barrier permeability.

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

DN-1289 Chemical Structure

CAS No. : 3026597-15-6

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References
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Description

IC₅₀ & Target

IC50: 17 nM (DLK), 40 nM (LZK)^[1]

In Vitro

DN-1289 (compound 14) (0.1, 0.3, and 1 μM; 0-20 h) can block axon degeneration in dorsal root ganglion (DRG) neurons induced by nerve growth factor (NGF) withdrawal^[1].
DN-1289 (0.1, 0.3, and 1 μM; 0-20 h) inhibits the activation of caspases in DRG neurons over time induced by NGF withdrawal^[1].

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

In Vivo

DN-1289 (compound 14) (100 mg/kg and 150 mg/kg; i.p.; once daily for 10-15 d) is well-tolerated in mice model^[1].
DN-1289 (150 mg/kg; p.o.; b.i.d. for 10 d) inhibits phosphorylation of c-Jun in an acute injury model with optic nerve crush (ONC) application^[1].

Pharmacokinetic Analysis^[1]

Species	Route	Dose (mg/kg)	plasma C_max (μM)	plasma AUC_{0-24 h} (μM·h)	CL_p (mL/min/kg)	CL_u (mL/min/kg)	V_d (L/kg)	t_1/2 (h)	F (%)	Kp_uu (AUC)	brain AUC_{0-2 h} (μM·h)
rat	IV	1	1.09	2.42	14.7	150	6.7	6.5	/	0.6	4.05
	PO	3	0.58	3.9	/	/	/	4.6	52	/	/
mouse	IV	1	1.06	4.06	8.6	200	4.7	6.8	/	/	/
	PO	10	2.32	21.9	/	/	/	7.9	56	0.4	6.91
	PO	150	24.9	324	/	/	/	23.7	53	/	/
	IP	100	15.4	280	/	/	/	23.7	53	/	/
cyno	IV	0.5	0.746	2.79	6.1	64	3.4	7.9	/	/	/

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

Molecular Weight

441.38

Formula

C₁₈H₁₉F₄N₇O₂

CAS No.

3026597-15-6

SMILES

NC1=C(OC(F)F)N=C(C2=NC(N3[C@@H](C4)CO[C@@H]4C3)=NC(N5CCC(F)(F)C5)=C2)C=N1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

Handling Instructions (2659 KB)

References

[1]. Craig RA 2nd, et al. Discovery of Potent and Selective Dual Leucine Zipper Kinase/Leucine Zipper-Bearing Kinase Inhibitors with Neuroprotective Properties in In Vitro and In Vivo Models of Amyotrophic Lateral Sclerosis. J Med Chem. 2022 Dec 22;65(24):16290-16312. [Content Brief]

DN-1289 Related Classifications

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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

DN-12893026597-15-6DN1289DN 1289JNKc-Jun N-terminal kinaseInhibitorinhibitorinhibit

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